900000000000509007: United States of America English language reference set (foundation metadata concept)

SNOMED CT Concept\SNOMED CT Model Component\Foundation metadata concept (foundation metadata concept)\Reference set\Language type reference set (foundation metadata concept)\English [International Organization for Standardization 639-1 code en] language reference set (foundation metadata concept)\US English

Status: current, Not sufficiently defined by necessary conditions definition status (core metadata concept). Date: 31-Jan 2002. Module: SNOMED CT model component module (core metadata concept)

Descriptions:

Expanded Value Set

Outbound Relationships	Type	Target	Active	Characteristic	Refinability	Group	Values
US English	Is a	English [International Organization for Standardization 639-1 code en] language reference set (foundation metadata concept)	true	Inferred relationship	Some

Members	acceptabilityId
A rare isolated constitutional thrombocytopenia characterized by reduced platelet count and defective platelet ATP secretion, resulting in increased bleeding tendency. Clinical manifestations are easy bruising, gum bleeding, menorrhagia, spontaneous epistaxis, spontaneous muscle hematoma and potential postpartum hemorrhage among others.	Preferred (foundation metadata concept)
A rare isolated constitutional thrombocytopenia with characteristics of neonatal onset of small-platelet thrombocytopenia with significantly increased bleeding tendency. Bleeding symptoms include petechial rash, mucosal bleeding, and heavy menstrual bleeding. Growth and development are normal, and there is no increased susceptibility to infections.	Preferred (foundation metadata concept)
A rare isolated hereditary giant platelet disorder characterized by severe thrombocytopenia and thrombopathy due to defects in proplatelet formation and platelet activation in homozygous patients. Clinical manifestations are recurrent bleeding episodes including epistaxis, spontaneous hematoma and menorrhagia.	Preferred (foundation metadata concept)
A rare isolated nail anomaly with characteristics of claw-shaped thick hyperplastic hard and hyperpigmented nails, subungual hyperkeratosis, onycholysis and slow nail growth. Variable degree of disease severity has been reported. There is evidence the disease can be caused by homozygous mutation in the FZD6 gene on chromosome 8q22.3-q23.1.	Preferred (foundation metadata concept)
A rare junctional epidermolysis bullosa subtype characterized by late-onset blistering surrounded by erythema and localized on the anterior aspect of the lower legs, associated with dystrophic toenails, tooth enamel defects and mild to severe intellectual disability. Lens subluxation and mild facial dysmorphism (with short midface, prognathism and thin upper lip vermilion) are additional reported features. There have been no further descriptions in the literature since 1992.	Preferred (foundation metadata concept)
A rare juvenile idiopathic inflammatory myopathy characterized by the association of inflammatory myositis (manifesting with acral erythema, progressive weakness of the limbs, pain, general fatigue, moodiness or crankiness) with clinical and/or laboratory features of other autoimmune diseases (for example systemic lupus erythematosus, localized scleroderma, diabetes). Cardiac involvement has been reported in some patients.	Preferred (foundation metadata concept)
A rare larynx anomaly with a cyst involving the larynx or supraglottis locations, such as the epiglottis and vallecula. Timing and severity of presentation depend on the size of the cyst and its proximity to the glottis and range from severe prenatal airway obstruction leading to polyhydramnios and pulmonary hypoplasia to postnatal inspiratory stridor associated with muffled cry, hoarseness and cyanotic episodes, feeding difficulties and failure to thrive. It can be associated with laryngomalacia.	Preferred (foundation metadata concept)
A rare late adult-onset myofibrillar myopathy with characteristics of progressive distal muscle weakness associated with peripheral neuropathy and hyporeflexia. Ambulation may be lost within a few years.	Preferred (foundation metadata concept)
A rare late-onset neurodegenerative disease with characteristics of supranuclear gaze palsy, postural instability, progressive rigidity, and mild dementia. Five clinical variants have been described with clinicopathological correlations, with Richardson's syndrome the most common clinical variant. The disease has neuropathological manifestations of neuronal loss, gliosis with astrocytic plaques and accumulation of tau-immunoreactive neurofibrillary tangles in specific brain areas. The differences in the rate and areas of accumulation of phosphorylated tau protein correlate with the five clinical variants. The disease is a 4R tauopathy composed of a preponderance of four-repeat (exon 10 positive) tau isoforms and a characteristic biochemical profile (doublet tau 64 and tau 69). The MAPT H1-clade specific sub-haplotype, H1c, is a risk factor for this disease.	Preferred (foundation metadata concept)
A rare lethal congenital myopathy syndrome characterized by decreased fetal movements and polyhydramnios in utero and the presence of akinesia, severe hypotonia with respiratory insufficiency, absent reflexes, joint contractures, skeletal abnormalities with thin ribs and bones, intracranial and retinal hemorrhages and decreased birth weight in the neonate.	Preferred (foundation metadata concept)
A rare lethal developmental defect during embryogenesis with characteristics of severe fetal malformations. These malformations include craniofacial dysmorphism (abnormal cyst in the cranial region, hypoplastic eyeballs, two orifices in the nasal region separated by a nasal septum, abnormal orifice replacing the mouth), omphalocele and immotile hypoplastic limbs encased under an abnormal, transparent membrane-like skin. Additional features include absence of adnexal structures of the skin on the outer aspect of the limbs, as well as underdeveloped skeletal muscles and bones. Association with tetralogy of Fallot, horseshoe kidneys, diaphragm and lung lobulation defects is reported.	Preferred (foundation metadata concept)
A rare lethal multiple congenital anomalies/dysmorphic syndrome with the association of fetal akinesia sequence, bilateral microphthalmia, microtia and persistent truncus arteriosus. Additional dysmorphic features include prominent forehead, small nose, micrognathia, as well as camptodactyly and symphalangism. Contractures of large joints and micropenis have also been reported.	Preferred (foundation metadata concept)
A rare lethal primary bone dysplasia with characteristics of fetal akinesia, multiple contractures, shortening of all long bones, short, broad ribs, narrow chest and thorax, pulmonary hypoplasia and a protruding abdomen. Short bowed femurs may also be associated.	Preferred (foundation metadata concept)
A rare leukodystrophy characterized by a spectrum of progressive neurologic manifestations comprising rapidly progressive early-onset nystagmus, spastic tetraplegia and visual and hearing impairment, resulting in death in early childhood, as well as later onset of slowly progressive complex spastic ataxia with pyramidal and cerebellar symptoms and loss of developmental milestones. Brain imaging shows diffuse hypomyelination of the subcortical and deep white matter, cerebellar atrophy and diffuse spinal cord volume loss.	Preferred (foundation metadata concept)
A rare leukodystrophy characterized by infantile onset of lower limb spasticity and severe developmental delay associated with delayed myelination and periventricular white matter abnormalities. Other reported signs and symptoms include microcephaly, optic atrophy, nystagmus, ataxia, or seizures.	Preferred (foundation metadata concept)
A rare life threatening acquired neurologic disease with characteristics of neuromyotonia, dysautonomia and encephalopathy with severe insomnia. Signs involving central (e.g. hallucinations, confusion, amnesia, myoclonus), autonomic (e.g. variations in blood pressure, hyperhidrosis) and peripheral (e.g. painful cramps, myokymia) hyperactivity, as well as systemic manifestations (such as weight loss, pruritus, fever), are reported. Thymoma is present in some cases.	Preferred (foundation metadata concept)
A rare life threatening disorder characterized by infection of the submucosal and muscular layers of the gastrointestinal tract.	Preferred (foundation metadata concept)
A rare life-threatening autoinflammatory syndrome with immune deficiency disorder characterized by early-onset life-long inflammation affecting the skin and bowel associated with recurrent infections. Presents with perioral and perianal psoriasiform erythema and papular eruption with pustules, failure to thrive associated with chronic malabsorptive diarrhea, intercurrent gastrointestinal infections and feeding troubles, as well as absent, short or broken hair and trichomegaly. Recurrent cutaneous and pulmonary infections lead to recurrent blepharitis, otitis externa and bronchiolitis.	Preferred (foundation metadata concept)
A rare life-threatening congenital non-syndromic conotruncal heart malformation with characteristics of absent or severely undeveloped pulmonary valve leaflets (with a restrictive ring of thickened tissue at the place of the pulmonary valve annulus) associated with an intact ventricular septum and a patent ductus arteriosus, manifesting with marked respiratory insufficiency. Additional features include dilated main pulmonary artery (with or without dilatation of pulmonary artery branches), to-and-fro flow at site of the dysplastic pulmonary valve and systolic pressure gradient across narrowed pulmonary valve. Tricuspid atresia and variable extra-cardiac anomalies (for example diaphragmatic hernia or cleft lip/palate) may be present.	Preferred (foundation metadata concept)
A rare life-threatening cutaneous disease characterized by a keratinocytic epidermal nevus presenting thick, hystrix-like, white or brownish hyperkeratosis associated with multiple extracutaneous vascular malformations, including angiodysplasia that involves large-vessel arteriovenous shunts that may be fatal during the neonatal period.	Preferred (foundation metadata concept)
A rare life-threatening genetic coagulation disorder with characteristics of an increased risk of blood clot formation in several members of a family due to a thrombomodulin gene mutation. Patients may manifest with venous thromboembolic disease, premature myocardial infarction and/or arterial thrombosis.	Preferred (foundation metadata concept)
A rare life-threatening intoxication with monochloroacetic acid (mainly through the skin, but also by inhalation or ingestion). It is characterized by vomiting, diarrhea and central nervous system excitability (disorientation, delirium, convulsions) as early signs of systemic poisoning, followed by central nervous system depression, coma and cerebral edema. Additional signs include heart involvement (severe myocardial depression, shock, arrhythmias, nonspecific myocardial damage), severe metabolic acidosis, hypokalemia and hypocalcemia and progressive renal failure leading to anuria. Myoglobinemia and leukocytosis may occur. Manifestations may be delayed for 1-4 hours.	Preferred (foundation metadata concept)
A rare life-threatening mitochondrial DNA depletion syndrome disease with characteristics of severe progressive sensorimotor neuropathy associated with corneal ulceration, scarring or anesthesia, acral mutilation, metabolic and immunologic derangement and hepatopathy (which can manifest with fulminant hepatic failure, a Reye-like syndrome or indolent progression to liver cirrhosis, depending on clinical form involved), present in the Navajo Native American population. Clinical presentation includes failure to thrive, distal limb weakness with reduced sensation, limb contractures with loss of function, areflexia, recurrent metabolic acidosis with intercurrent illness, immunologic anomalies manifesting with severe systemic infections and sexual infantilism.	Preferred (foundation metadata concept)
A rare life-threatening neurometabolic disease with characteristics of a progressive neurodegenerative course, epilepsy, retinopathy and progressive cardiomyopathy.	Preferred (foundation metadata concept)
A rare life-threatening non-inflammatory vasculopathy disorder characterized by diffuse precipitation of calcium in viscera (mainly in the heart or lungs, but also in the stomach or kidneys) leading to fibrosis and thrombosis, which eventually cause necrotic ulcerations of the tissue. Patients may present with dyspnea, cough and respiratory failure or acute heart block and subsequent sudden cardiac death, depending on the affected organ. The disease mainly affects patients on dialysis or patients having undergone renal transplantation.	Preferred (foundation metadata concept)
A rare lipoprotein metabolism disorder characterized clinically by corneal opacities and sometimes renal failure and hemolytic anemia, and biochemically by severely reduced HDL cholesterol. Age of onset is variable but most patients are diagnosed during adulthood. Two familial forms of LCAT deficiency have been reported: familial LCAT deficiency characterized by corneal opacities, anemia and renal insufficiency, and Fish-eye disease characterized by corneal opacities and sometimes atherosclerosis. LCAT deficiency is caused by deficient or absent catalytic activity of the LCAT enzyme, which catalyzes the formation of cholesterol esters in lipoproteins and is encoded by the LCAT gene (16q22.1). Accumulation of unesterified cholesterol in the body for example in the cornea, erythrocytes and kidneys, is thought to underlie the clinical manifestations.	Preferred (foundation metadata concept)
A rare lipoprotein metabolism disorder with biochemical characteristics of an almost complete absence of plasma high-density lipoproteins (HDL) and clinical characteristics of liver, spleen, lymph node and tonsil enlargement along with peripheral neuropathy in children and adolescents and occasionally cardiovascular disease in adults. Approximately 100 cases have been described worldwide. The disease is due to mutations in the ABCA1 gene (9q31) encoding the ATP-binding cassette transporter (ABC1), a cholesterol efflux regulatory protein that is able to orient cellular cholesterol towards the cell surface and to facilitate its transfer towards the core of HDL. Mutations in this gene result in severe deficiency of plasma HDL cholesterol and deposition of cholesteryl and retinyl esters and carotenoids in nonadipose tissues. Transmission is autosomal recessive.	Preferred (foundation metadata concept)
A rare localized lipodystrophy characterized by the appearance of asymptomatic, well-demarcated, variably sized, depressed, lipoatrophic lesions secondary to subcutaneous, intradermic or intramuscular drug injection, including corticosteroids, insulin, human growth hormone and antibiotics. Skin coloration may vary from white or hypopigmented to reddish, pinkish or violaceous. Epidermal atrophy may be also present.	Preferred (foundation metadata concept)
A rare localized variant of Guillain-Barré syndrome characterized by rapidly progressive bilateral facial nerve palsy, distal paresthesia and minimal or no motor weakness. Deep tendon reflexes are usually diminished or absent but can be present or even exaggerated in rare cases. Cerebrospinal fluid analysis may reveal albuminocytologic dissociation. Nerve conduction velocity studies often show demyelinating type of neuropathy although axonal polyneuropathy has been also described.	Preferred (foundation metadata concept)
A rare lymphatic system anomaly with characteristics of multifocal congenital and progressive vascular lesions of the skin, gastrointestinal tract and occasionally other anatomic sites, causing potentially life-threatening thrombocytopenic coagulopathy. Macroscopically the lesions appear as round to oval red-brown plaques and as large as a few centimeters in diameter. Histopathologically they consist of dilated thin-walled vessels with variable endothelial hyperplasia, positive for lymphatic endothelial cell markers and resembling benign lymphangioendothelioma.	Preferred (foundation metadata concept)
A rare lymphoid hemopathy defined as single or multiple tumors in the bone, not associated with infringement or violation of other extranodal malignant lymph nodes outside the area. It usually presents with bone pain, nerve compression, a palpable mass or fracture, while systemic features (fever, night sweats, fatigue, loss of appetite, weight loss) are not common.	Preferred (foundation metadata concept)
A rare lymphoma of the lung defined as a clonal lymphoid proliferation affecting one or both lungs in a patient with no detectable extrapulmonary involvement at diagnosis or during the subsequent 3 months. Comprises low grade/indolent B cell forms, the most frequent form represented by the marginal B-cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and other non-MALT low grade lymphomas; and more rarely high-grade B-cell and lymphomatoid granulomatosis. Very rare and represents only 3-4% of extranodal non-Hodgkin lymphoma.	Preferred (foundation metadata concept)
A rare lymphoma with concurrent occurrence of two or more histologic types of lymphoma involving the same anatomic site. Composite lymphomas can be combinations of two non-Hodgkin lymphomas or of a non-Hodgkin and a Hodgkin lymphoma. In many cases, the neoplasms are clonally related. Clinical presentation and treatment are determined by the more aggressive component.	Preferred (foundation metadata concept)
A rare macular disorder with characteristics mostly of a variable degree of decreased visual acuity, jerk or pendular nystagmus and typical ocular findings at imaging. The disease is usually bilateral. Rarely nystagmus can be absent. Locally the disease has characteristics of an underdeveloped foveal pit, absence of foveal pigmentation and/or foveal avascular zone and persistence of inner retinal layers at the fovea in absence of concomitant ocular or systemic pathology.	Preferred (foundation metadata concept)
A rare malformation syndrome affecting the apical structures of digits and presenting with hypo/aplasia of nails and distal phalanges. Cooks syndrome is congenital and presents with hypo/anonychia, small or absent distal phalanges and digitalization of the thumbs. Usually, the nails of digits 1-3 are progressively deformed, with anonychia congenita totalis in the digits 4-5 and in all toes. Additional features include hypoplasia of the distal phalanges in digits 2-4 with absence of the distal phalanx of digit 5. In the feet, there is absence of all distal phalanges of digits 2-5 with hypoplasia of the distal phalanx of digit 1.	Preferred (foundation metadata concept)
A rare malformation syndrome with multiple congenital abnormalities, described in 2 siblings, with characteristics of VATER-like association in combination with pulmonary hypertension, laryngeal webs, blue sclerae, abnormal ears, persistent growth deficiency and normal intellect.	Preferred (foundation metadata concept)
A rare malformation with a soft, fluctuant mass, abscess or draining tract along the anterior border of the lower half of sternocleidomastoid muscle, occasionally leading to development of retropharyngeal abscess, acute suppurative thyroiditis, stridor, respiratory distress, odynophagia and dysphagia. Anomaly occurs as a tract from the piriform sinus to the thyroid gland. A fourth branchial cleft fistula passes deep to the superior laryngeal nerve but superficial to the recurrent laryngeal nerve, which is the main difference in comparison to the third branchial cleft fistula.	Preferred (foundation metadata concept)
A rare malformation with characteristics of a soft, fluctuant mass, abscess or draining tract along the anterior border of the lower half of sternocleidomastoid muscle, occasionally leading to development of retropharyngeal abscess, acute suppurative thyroiditis, stridor, respiratory distress, odynophagia and dysphagia. Anomaly occurs as a tract from the piriform sinus to the thyroid gland. A third branchial cleft fistula passes superficial to both the superior and recurrent laryngeal nerves, which is the main difference in comparison to the fourth branchial cleft fistula.	Preferred (foundation metadata concept)
A rare malignant germ cell tumor of ovary arising from germ cells in the ovary, frequently unilateral at diagnosis, usually presenting during adolescence with pelvic mass, fever, vaginal bleeding and acute abdomen, with certain subtypes being occasionally associated with isosexual precocity, virilization, hyperthyroidism or carcinoid syndrome. Histologically they comprise the following: embryonal carcinoma, yolk sac tumor, polyembryoma and mixed germ cell tumor.	Preferred (foundation metadata concept)
A rare malignant germ cell tumor that occur in the midline of the body as a result of abnormal germ cell migration during embryogenesis. Clinical manifestations are variable and depend on the location and size of the tumor. Central nervous system tumor might present with headache, visual disturbances, endocrine abnormalities, and signs of increased intracranial pressure. A mediastinal tumor commonly presents with chest pain, dyspnea, cough and fever. Abdominal mass with or without pain, backache and weight loss are common clinical presentations in retroperitoneal tumor.	Preferred (foundation metadata concept)
A rare malignant hematologic disease characterized by clonal proliferation of myeloid blasts, primarily involving the bone marrow, in association with congenital disorders (e.g. Fanconi anemia, dyskeratosis congenita, Bloom syndrome, Down syndrome, congenital neutropenia, neurofibromatosis) and genetic defects predisposing to acute myeloid leukemia. Patients present with signs and symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Depending on the underlying genetic defect, there may be additional cancer risks and other health problems present.	Preferred (foundation metadata concept)
A rare malignant mesenchymal tumor of smooth muscle origin characterized histologically by spindle and/or pleomorphic cells, often forming disorganized fascicles, with tumor cell necrosis. Macroscopic characteristics are a large soft usually intramural mass with irregular borders and necrotic and hemorrhagic areas located in the uterus. Presenting signs and symptoms typically include dysfunctional vaginal bleeding, vaginal discharge, palpable pelvic mass and/or pelvic pain/pressure. Changes in bowel habits, frequent or painful urination and hematuria may also be associated.	Preferred (foundation metadata concept)
A rare malignant mesenchymal tumor of smooth muscle origin, macroscopically appearing as a large, poorly circumscribed mass, often protruding from the cervical canal or expanding it circumferentially. The most common presenting symptoms are vaginal discharge or bleeding, pain in the lower abdomen and a bulky cervical mass. There is a reported tendency to metastasize hematogenously, especially to the lungs, peritoneum, bones and the liver.	Preferred (foundation metadata concept)
A rare malignant neoplastic disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring rearrangements in the PDGFRA gene, in the blood, bone marrow and often other tissues as well (spleen, lymph nodes, skin). It usually presents as chronic eosinophilic leukemia or, less commonly, as acute myeloid leukemia or T-lymphoblastic leukemia with eosinophilia. Patients usually present with eosinophilia, anemia, thrombocytopenia, neutrophilia, splenomegaly, lymphadenopathy, fever, sweating and/or weight loss. Tissue infiltration by eosinophils can manifest with skin rash, erythema, cough, neurological alterations, gastrointestinal symptoms or, rarely, endomyocardial fibrosis and restrictive cardiomyopathy.	Preferred (foundation metadata concept)
A rare malignant primary thymic neoplasm originating from neuroendocrine cells presenting as a mass within the anterior mediastinum. Patients typically present with nonspecific symptoms, such as chest pain, cough, shortness of breath or in some cases superior vena cava syndrome. Patients could be asymptomatic during the early stages or present with multiple endocrine neoplasia type I. Ectopic production of ACTH and serotonin can lead to Cushing syndrome and carcinoid syndrome respectively.	Preferred (foundation metadata concept)
A rare malignant sex cord stromal tumor of ovary occurring typically in young women and characterized by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea) when functional.	Preferred (foundation metadata concept)
A rare malignant tumor of the peritoneal cavity of extra-ovarian origin. Clinically and histologically similar to advanced-stage serous ovarian carcinoma. It is almost exclusively found in women. Can occur many years after oophorectomy performed for benign diseases or prophylactic oophorectomy. The tumor develops in the peritoneum and spreads to the abdomen, pelvis and ovaries.Primary peritoneal carcinoma has an epithelial origin and probably derives from embryonal epithelium. The fallopian tubes are suspected as the primary site.	Preferred (foundation metadata concept)
A rare mandibulofacial dysostosis with the association with scalp alopecia and sparse eyebrows and eyelashes. Craniofacial dysmorphic features include zygomatic and mandibular dysplasia or hypoplasia, cleft palate, micrognathia, dental anomalies, auricular dysmorphism and eyelid anomalies among others. Patients may experience limited jaw mobility, glossoptosis, upper airway obstruction and conductive hearing loss.	Preferred (foundation metadata concept)
A rare maternal disease-related embryofetopathy with characteristics of variable developmental anomalies of the fetus due to teratogenic effect of elevated maternal body temperature (resulting from febrile illness or hot environment exposure). Reported developmental anomalies include neural tube defects (spina bifida, encephalocele, anencephaly), cardiac defects (transposition of great vessels), urogenital defects (hypospadias), abdominal wall defects, cleft lip/palate, eye defects (cataract, coloboma) or various minor anomalies (for example bifid uvula, preauricular pit or tag). Consensus regarding cause and effect relationship has not been reached.	Preferred (foundation metadata concept)
A rare maxillofacial disorder with characteristics of significant reduction in mouth opening in the absence of acquired factors (e.g. trauma, infection) contributing to the ankylosis. It is associated with variable degrees of facial dysmorphism (i.e. lateral deviation of the mandible and chin, lower facial asymmetry, retrognathia, micrognathia, dental malocclusion) and patients typically present with feeding and breathing difficulties. Developmental delay, hypotonia, seizures, and additional dysmorphic features (e.g. pectus excavatum, low-set ears, hypoplastic alae nasi) have also been reported.	Preferred (foundation metadata concept)
A rare medullar disease defined as a development of a fluid-filled cavity or syrinx within the spinal cord due to blockage of cerebrospinal fluid circulation (for example due to basal arachnoiditis, meningeal carcinomatosis, various mass lesions), spinal cord injury (for example due to trauma, radiation necrosis, spinal abscess), spinal dysraphism or intramedullary neoplasm. It presents with neuropathic pain, numbness, muscular weakness, changes in tone or spasticity or autonomic changes (hyperhidrosis, heart rate or blood pressure instability). Selective loss of pain and temperature with relative preservation of dorsal column function (touch and pressure) are classic findings.	Preferred (foundation metadata concept)
A rare metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD). This condition usually presents in early childhood and the manifestations are variable. The disease is caused by mutations in the malonyl-CoA decarboxylase gene (MLYCD, chromosome 16q24) and is inherited as an autosomal recessive trait. The MCD enzyme is involved in the degradation of malonyl-CoA and it appears that inhibition of fatty acid synthesis as a result of malonyl-CoA accumulation is responsible for at least some of the clinical manifestations of the disorder.	Preferred (foundation metadata concept)
A rare metabolic myopathy with characteristics of episodic myalgia with myoglobinuria which is induced by fever, viral or bacterial infection, prolonged exercise or alcohol abuse, and could, on occasion, lead to acute renal failure. Between episodes, patients may be asymptomatic or could present elevated creatine kinase levels and mild muscle weakness. There have been no further descriptions in the literature since 1997.	Preferred (foundation metadata concept)
A rare metabolic myopathy with characteristics of muscle cramping and/or stiffness after exercise (especially during heat exposure), post-exertional rhabdomyolysis and myoglobinuria and elevation of serum creatine kinase. Caused by mutation in the SLC16A1 gene.	Preferred (foundation metadata concept)
A rare metabolite absorption and transport disorder with characteristics of moderate increase of methylmalonic acid (MMA) in the blood and urine due to decreased cellular uptake of cobalamin resulting from decreased transcobalamin receptor function. Patients are usually asymptomatic however; screening reveals increased C3-acylcarnitine and MMA in plasma. Serum homocysteine levels may vary from normal to moderately elevated and retinal vascular occlusive disease, resulting in severe visual loss, has been reported. Caused by mutation in the gene encoding the transcobalamin receptor (CD320).	Preferred (foundation metadata concept)
A rare microdeletion syndrome associated with a distinct facial appearance. It has been reported in four unrelated patients. A mask-like facial appearance is the most characteristic feature with blepharophimosis, tight appearing glistening facial skin, flat and broad nose, dysplastic ears and unusual scalp hair pattern. Camptodactyly, joint contractures, unusual dentition and mild developmental delay can be observed. Cryptorchidism in boys and a happy disposition are constant.	Preferred (foundation metadata concept)
A rare midline cerebral malformation disorder with characteristics of duplicated pituitary stalks and/or glands within duplicated sella. Patients may present various degrees of facial dysmorphism and endocrine abnormalities, including precocious puberty, hypogonadism, hypothyroidism and/or hyperprolactinemia, as well as associated congenital anomalies such as cleft lip/palate, bifid nasal bridge/tongue/uvula, hypothalamic enlargement with or without hamartoma, nasopharyngeal tumors, corpus callosum agenesis/hypoplasia, basilar artery duplication, and/or vertebral defects (in particular duplication of the odontoid process).	Preferred (foundation metadata concept)
A rare mild form of galactosemia characterized by early onset of cataract and an absence of the usual signs of classic galactosemia, i.e. feeding difficulties, poor weight gain and growth, lethargy and jaundice. Patients generally have elevated plasma galactose and increased urinary excretion of galactitol. They develop cataracts during the first weeks or months of life as a result of accumulation of galactitol in the lens. Patients are otherwise healthy. Caused by mutations in the GALK1 gene (17q24) coding for the galactokinase enzyme. The disorder is inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A rare mitochondrial DNA depletion syndrome with characteristics of congenital or early-onset lactic acidosis, hypotonia and severe global developmental delay with feeding difficulties and failure to thrive. It is frequently associated with variable dysmorphic facial features. Additional manifestations include seizures, movement disorders and cardiac and ophthalmologic anomalies, among others. Brain imaging may show generalized atrophy and white matter abnormalities.	Preferred (foundation metadata concept)
A rare mitochondrial DNA depletion syndrome with characteristics of neonatal or infantile onset of global developmental delay, hypotonia, failure to thrive, progressive neurologic decline, sensorineural deafness and movement disorder. Seizures, external ophthalmoplegia, polyneuropathy, cardiomyopathy, and renal tubular dysfunction have also been reported. Brain imaging may show T2-weighted hyperintensities in the basal ganglia and laboratory examination may reveal lactic acidosis and mild methylmalonic aciduria.	Preferred (foundation metadata concept)
A rare mitochondrial DNA maintenance syndrome with characteristics of early-onset cerebellar ataxia and a variable combination of epilepsy, headache, dysarthria, ophthalmoplegia, peripheral neuropathy, intellectual disability, psychiatric symptoms and movement disorders.	Preferred (foundation metadata concept)
A rare mitochondrial disease characterized by a variable phenotype of congenital sensorineural deafness, intermittent or persistent hypoglycemia and hepatic and renal dysfunction potentially progressing to organ failure. Serum lactate levels are variably increased, deficiency of mitochondrial respiratory chain complexes I, III, and IV is observed in the liver and in fibroblasts.	Preferred (foundation metadata concept)
A rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, hyperlactatemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiencies of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.	Preferred (foundation metadata concept)
A rare mitochondrial disease characterized by early infantile onset of progressive neurological deterioration with seizures, spasticity and lack of psychomotor development. Brain imaging shows severe leukodystrophy and abnormalities of neuronal migration. Lactic acidosis is common. The disease is usually fatal in early childhood.	Preferred (foundation metadata concept)
A rare mitochondrial disease characterized by infantile onset of severe regression after a period of normal development, epileptic encephalopathy, hypotonia, movement disorder, cardiomyopathy, hyperglycinemia and lactic acidosis. Optic atrophy may also be present. Brain imaging findings are highly variable and include white matter abnormalities. The disease is typically fatal in infancy. Caused by homozygous mutation in the BOLA3 gene on chromosome 2p13.	Preferred (foundation metadata concept)
A rare mitochondrial disease characterized by prenatal complications including oligohydramnios, fetal growth restriction, hydrops, and anemia. This is followed by severe lactic acidosis, hyaline membrane disease, pulmonary hypertension, cardiac anomalies, liver dysfunction, urogenital abnormalities and progressive renal disease, seizures, thrombocytopenia, and sideroblastic anemia resulting in multisystem organ failure and death shortly after birth. Less severely affected patients that survive the neonatal period have been reported to have sensorineural hearing loss and developmental delay.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in coenzyme Q10 biosynthesis that manifests with a broad spectrum of signs and symptoms which may include: neonatal lactic acidosis, global developmental delay, tonus disorder, seizures, reduced spontaneous movements, ventricular hypertrophy, bradycardia, renal tubular dysfunction with massive lactic acid excretion in urine, severe biochemical defect of respiratory chain complexes II/III when assayed together and deficiency of coenzyme Q10 in skeletal muscle. Cerebral and cerebellar atrophy can be seen on magnetic resonance imaging and multiple choroid plexus cysts and symmetrical hyperechoic signal alterations in basal ganglia have been observed on ultrasound.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly. Laboratory studies report increased plasma lactate and alanine, abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, III, IV, and V. Caused by compound heterozygous mutation in the MRPL3 gene on chromosome 3q22.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy, ophthalmoplegia and reduced vision). Additional manifestations include bulbar paresis with facial weakness, hypotonia, difficulty chewing, dysphagia, mild dysarthria, ataxia, global muscle atrophy, and areflexia. It has a relatively slow disease progression with patients often living into the third decade of life.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with characteristics of neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis. Additional manifestations reported include poor feeding, failure to thrive, microcephaly, hypotonia, anemia and thrombocytopenia. Caused by homozygous or compound heterozygous mutation in the FARS2 gene on chromosome 6p25.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with characteristics of normal early development followed by the sudden onset in infancy of poor feeding, dysphagia, truncal (followed by global) hypotonia, motor regression, abnormal movements (i.e. severe dystonia of limbs, choreoathetosis, facial dyskinesia) and reduced tendon reflexes. The disease course is severe but nonprogressive.	Preferred (foundation metadata concept)
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with onset in infancy or early childhood of muscular hypotonia, gait ataxia, mild bilateral pyramidal tract signs, developmental delay (affecting mostly speech and coordination) and subsequent intellectual disability. Short stature, obesity, microcephaly, strabismus, nystagmus, reduced visual acuity, lactic acidosis, and a brain neuropathology consistent with Leigh syndrome are also reported. Caused by homozygous or compound heterozygous mutation in the MTFMT gene on chromosome 15q22.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of a distinctive MRI pattern of cavitating leukodystrophy, predominantly in the posterior region of the cerebral hemispheres. The clinical picture varies widely between acute neurometabolic decompensation in infancy with loss of developmental milestones, seizures and pyramidal signs rapidly evolving into spastic tetraparesis, to subtle neurological symptoms presenting in adolescence. The disease course tends to stabilize over time in most patients and marked recovery of milestones may be observed.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of a highly variable phenotypic spectrum comprising delayed motor development, peripheral neuropathy, cataract, short stature due to growth hormone deficiency, nystagmus, sensorineural hearing loss, dysmorphic facial features and skeletal abnormalities consistent with spondyloepimetaphyseal dysplasia. Hyperextensible joints, achalasia and telangiectasia have also been described. Cognition is normal. Atrophy of the pituitary gland has been observed in brain imaging.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of a variable clinical phenotype ranging from fetal hydrops and postnatal hypotonia, bradycardia and respiratory failure, resulting in death in the neonatal period, to infantile onset of episodes of acute cardiopulmonary failure associated with severe lactic acidosis and slowly progressive muscle weakness. Muscle biopsy shows reduced activity of mitochondrial complexes I, III, and IV.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of a variable clinical phenotype with the core features of optic atrophy, ataxia and hypotonia. Additional common manifestations include global developmental delay with or without regression, neuropathy, spasticity, and microcephaly, less frequently seizures, movement disorder, hearing loss and respiratory failure. Brain imaging may show abnormalities of the corpus callosum, basal ganglia and midbrain, cerebral or cerebellar atrophy, or white matter abnormalities. The condition is frequently fatal at an early age.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of a variable phenotype comprising delayed psychomotor development or neurodevelopmental regression, hypotonia, seizures, microcephaly, optic atrophy, pyramidal signs, and peripheral neuropathy among others. Age of onset and disease severity is also variable with some cases taking a fatal course in early infancy. Serum lactate levels may be elevated. Reported brain imaging findings include abnormal signals in the basal ganglia, cerebral and/or cerebellar atrophy and white matter abnormalities.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, manifestations of spinocerebellar ataxia (e.g. impaired gait, dysarthria) and mild motor peripheral neuropathy. Respiratory insufficiency has been reported in some cases.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of bilateral auditory neuropathy and optic atrophy. Patients present hearing and visual impairment in the first or second decade of life, while psychomotor development is normal. Bilateral retinitis pigmentosa has been reported in association.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of early onset of hypertrophic cardiomyopathy and variable neurologic symptoms including global developmental delay, hypotonia, intellectual disability, visual impairment and seizures. Lactic acidosis is present in all patients. Muscle biopsy usually shows decreased activity of mitochondrial complexes I and IV. Brain imaging may reveal variable abnormal signal intensities in the thalamus, basal ganglia, and/or brain stem.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of exclusive skeletal muscle involvement without clinical evidence of other organ involvement. Disease manifestations are progressive limb weakness, proximal limb muscle atrophy and eye muscle anomalies (e.g. ocular motility restriction, ptosis). Patients may present with lactic acidosis, diffuse myalgia and overall fatigability (particularly during/after physical activities), dysphagia and diminished deep tendon reflexes.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of failure to thrive, infantile encephalopathy, muscular hypotonia, global developmental delay and regression, pulmonary arterial hypertension, episodes of apnea and bradycardia, respiratory failure, hyperglycinemia and lactic acidosis. Hypertrophic or dilated cardiomyopathy has also been reported. Brain imaging may show leukoencephalopathy involving variable regions. The disease is typically fatal in early infancy. Caused by homozygous or compound heterozygous mutation in the NFU1 gene on chromosome 2p13.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of neonatal onset of severe cardiac and/or neurologic signs and symptoms mostly associated with a fatal outcome in the neonatal period or in infancy, although a milder phenotype with later onset and slowly progressive neurologic deterioration has also been reported. Clinical manifestations are variable and include respiratory insufficiency, hypotonia, cardiomyopathy and seizures. Serum lactate is elevated in most cases. Brain imaging may show cerebellar atrophy or hypoplasia.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of onset of episodic developmental regression in the first year of life, often in the setting of febrile illnesses, as well as hypotonia and seizures or refractory epileptic encephalopathy. Other observed features include ataxia, dystonia or optic atrophy among others. Patients do not achieve independent ambulation or meaningful speech. Brain imaging may show progressive cerebellar or diffuse atrophy and signal abnormalities of the basal ganglia. Serum lactate is often elevated.	Preferred (foundation metadata concept)
A rare mitochondrial disease with characteristics of prenatal or early infantile onset of severe cardiomyopathy, failure to thrive and global developmental delay, sensorineural hearing loss and severe lactic acidosis. Hepatic involvement and adrenal insufficiency, as well as encephalopathy and anomalies of deep gray matter structures on brain MRI have also been reported.	Preferred (foundation metadata concept)
A rare mitochondrial disease with marked clinical variability typically and characteristics of encephalomyopathy, kidney disease (nephrotic syndrome), optic atrophy, early-onset deafness, pancytopenia, obesity, and cardiac disease (valvulopathy). Additionally, macrocephaly, intellectual disability, elevated lactate/pyruvate ratio, insulin-dependent diabetes, livedo reticularis, liver dysfunction and seizures have also been associated.	Preferred (foundation metadata concept)
A rare mitochondrial disease with signs and symptoms within a phenotypic and metabolic spectrum that includes global developmental delay, hypotonia, intellectual disability, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy, lactic acidosis, and increased excretion of Krebs cycle intermediates. Other variable features are spasticity, seizures, ataxia, congenital cataract, and dysmorphic facial features. Age of onset is in the neonatal period or infancy.	Preferred (foundation metadata concept)
A rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by severe intrauterine growth retardation, neonatal limb edema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe intractable neonatal lactic acidosis with lethargy, hypotonia, absent spontaneous movements and fatal outcome. Markedly decreased activity of complex I, II + III and IV in muscle and liver have been determined.	Preferred (foundation metadata concept)
A rare mitochondrial disorder due to a defect in mitochondrial protein synthesis with characteristics of neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy.	Preferred (foundation metadata concept)
A rare mitochondrial myopathy with characteristics of motor developmental delay (in infancy), growth impairment and mostly proximal muscle weakness caused by a muscular dystrophy. Muscle biopsy presents myopathic abnormalities and decreased mitochondrial deoxyribonucleic acid (mtDNA) content. Electromyography (EMG) shows a myopathic process and serum creatine kinase is increased. The disease also has characteristics of early onset non-progressive cerebellar atrophy (particularly cerebellar vermis and hemispheres), corticospinal tract dysfunction, and global or partial cerebral atrophy on brain MRI. Additionally, some patients presented with cognitive deficiencies, skeletal abnormalities, tremors and retinopathy. Caused by biallelic mutations in the MSTO1 gene located on chromosome 1q22 with autosomal recessive inheritance. In a very few cases, the pattern of inheritance is autosomal dominant.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder characterized by a highly variable phenotype which may present as exercise intolerance with prominent exertional dyspnea, progressive muscle weakness, spasticity and neuropathy, but without cognitive impairment or cardiac involvement, or as global developmental delay, growth retardation, hypotonia and spasticity. Hypertrophic cardiomyopathy, optic atrophy, seizures and dysmorphic facial features have also been reported in the more severe phenotype. Serum lactate may be elevated and muscle biopsy shows myopathic features and variably decreased activity of mitochondrial respiratory chain complexes.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder characterized by progressive generalized hypotonia, progressive external ophthalmoplegia and severe lactic acidosis, which result in early fatality (days to months after birth). Patients may present with lethargy and areflexia and may associate additional features, such as cardiomyopathy, renal dysfunction, liver involvement and seizures.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by onset of slowly progressive proximal lower limb weakness and exercise intolerance in the first decade of life, followed by weakness of neck flexor, shoulder and distal leg muscles. Facial muscles become involved still later in the disease course. Additional manifestations are restrictive pulmonary function and short stature. Laboratory studies reveal lactic acidemia and increased serum creatine kinase.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder due to nuclear deoxyribonucleic acid anomalies. The disease is characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with a variable clinical phenotype. Manifestations include infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder and liver involvement along with childhood onset of severe myoclonus epilepsy, cognitive decline, progressive hearing and visual impairment and progressive tetraparesis. Serum lactate may be increased and brain imaging shows variable atrophy and white matter abnormalities.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with a variable phenotype, including developmental delay with psychomotor regression, intellectual disability, epilepsy, Leigh syndrome, non-syndromic hearing loss, visual impairment and severe myopathy. Decreased activity of mitochondrial respiratory complexes and lactic acidosis are common findings and diffuse cerebral atrophy may be associated.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with characteristics of a highly variable clinical phenotype, including a benign infantile mitochondrial type affecting mainly the skeletal muscle, a lethal infantile mitochondrial myopathy linked to severe metabolic acidosis and mitochondrial dysfunction in skeletal muscle and often also in heart, Leigh syndrome, which causes severe, early-onset, progressive, and fatal encephalopathy and French-Canadian type Leigh syndrome, which affects mostly the skeletal muscle, but also brain and liver.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with characteristics of a spectrum of three main clinical phenotypes comprising a severe neonatal phenotype with early fatal lactic acidosis, a more protracted course with early-onset developmental delay, motor weakness, extrapyramidal signs with or without epilepsy and a phenotype with normal early development and Parkinson-like symptoms starting around the age of one year. Additional variably reported signs and symptoms include cardiomyopathy, optic anomalies, hepatosplenomegaly and abnormal brain MRI findings among others. Deficiencies in mitochondrial oxidative phosphorylation enzymes are inconsistent.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with characteristics of early onset of severe developmental delay (sometimes with regression of developmental milestones) and intellectual disability, poor or absent speech and hypotonia. Other features include movement disorder, seizures, or microcephaly, among others. Brain imaging may show features of Leigh syndrome with signal abnormalities in the basal ganglia or mid brain, cerebellar atrophy or thin corpus callosum.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with characteristics of microcephaly, global developmental delay, spastic-dystonic movement disorder, intractable seizures, optic atrophy, autonomic dysfunction and peripheral neuropathy. Serum lactate is increased, and muscle biopsy shows decreased activity of mitochondrial respiratory complexes I and III. Brain imaging reveals progressive cerebellar atrophy and delayed myelination.	Preferred (foundation metadata concept)
A rare mitochondrial oxidative phosphorylation disorder with characteristics of neonatal onset of hypotonia, feeding difficulties, deafness, and early fatal respiratory failure. Cardiac and liver involvement has been reported. Serum lactate is increased and metabolic studies show decreased activity of mitochondrial respiratory complexes I and IV in skeletal muscle.	Preferred (foundation metadata concept)

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Reference Sets

Reference set descriptor

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Id	Description	Lang	Type	Status	Case?	Module
900000000001115012	United States of America English language reference set	en	Synonym (core metadata concept)	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)
900000000001116013	US English	en	Synonym (core metadata concept)	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)
900000000001117016	United States of America English language reference set (foundation metadata concept)	en	Fully specified name	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)