{"Name":"Pyruvate dehydrogenase E3 deficiency","DiseaseID__c":"GARD:0003263","id":3263,"encodedName":"pyruvate-dehydrogenase-e3-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Pyruvate dehydrogenase E3 deficiency","Xref_IDs__c":"29914000; C5574660; MEDGEN:1805500; MONDO:0009529; OMIM:246900; ORPHA:2394","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":6,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":1,"Description_Source__c":"MONDO:0009529","Disease_Description__c":"Pyruvate dehydrogenase E3 deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by either early-onset lactic acidosis and delayed development, later-onset neurological dysfunction or liver disease.","GARD_Name__c":"Pyruvate dehydrogenase E3 deficiency","GARD_Synonym__c":"congenital infantile lactic acidosis due to lad deficiency; cytochrome-b reductase deficiency; deficiency of diaphorase; deficiency of dihydrolipoamide dehydrogenase; deficiency of lipoamide reductase (nadh); diaphorase deficiency; dihydrolipoamide dehydrogenase (e3) deficiency; dihydrolipoamide dehydrogenase deficiency; dihydrolipoamide dehydrogenase e3 deficiency; dihydrolipoyl dehydrogenase deficiency; dld - dihydrolipoamide dehydrogenase deficiency; dld deficiency; dldd; e3 deficiency; e3-deficient maple syrup urine disease; lactic acidosis due to lad deficiency; lipoamide dehydrogenase deficiency; lipoamide dehydrogenase deficiency, lactic acidosis due to; maple syrup urine disease with lactic acidosis; maple syrup urine disease, type iii","Curated_Disease_Description_Source__c":"GARD:0003263","Curated_Disease_Description__c":"Dihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals. A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures.  Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood glucose levels (hypoglycemia). Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Child","SourceID__c":"ORPHA:2394","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0009529","ORPHANET_ID__c":"ORPHA:2394","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Deficiencia de piruvato deshidrogenasa e3","Spanish_Description_Source__c":"ORPHA:2394","Spanish_Description__c":"El déficit de piruvato deshidrogenasa E3 es un subtipo muy raro de déficit de piruvato deshidrogensas (PDHD, consulte este término) caracterizado bien por una acidosis láctica de inicio precoz y retraso en el desarrollo, una disfunción neurológica de inicio tardío o una enfermedad hepática.","Spanish_Disease_Name__c":"deficiencia de piruvato deshidrogenasa e3","Spanish_GARD_Synonym__c":"deficiencia de dihidrolipoamida deshidrogenasa; deficiencia de dld; enfermedad de jarabe de arce con deficiencia de e3","Category_Linearization__c":"ORPHA:68367","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Dihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals. A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures.  Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood glucose levels (hypoglycemia). Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures.","Curated_Disease_Description_Source__c":"GARD:0003263","GARD_Synonym__c":"congenital infantile lactic acidosis due to lad deficiency; cytochrome-b reductase deficiency; deficiency of diaphorase; deficiency of dihydrolipoamide dehydrogenase; deficiency of lipoamide reductase (nadh); diaphorase deficiency; dihydrolipoamide dehydrogenase (e3) deficiency; dihydrolipoamide dehydrogenase deficiency; dihydrolipoamide dehydrogenase e3 deficiency; dihydrolipoyl dehydrogenase deficiency; dld - dihydrolipoamide dehydrogenase deficiency; dld deficiency; dldd; e3 deficiency; e3-deficient maple syrup urine disease; lactic acidosis due to lad deficiency; lipoamide dehydrogenase deficiency; lipoamide dehydrogenase deficiency, lactic acidosis due to; maple syrup urine disease with lactic acidosis; maple syrup urine disease, type iii","Name":"Pyruvate dehydrogenase E3 deficiency","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Metabolic Support UK","Website__c":"https://www.metabolicsupportuk.org"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Neurology","Tag_Category__c":"Disease Category;Specialist","category_description":"Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.","curated_tag_name":"Neurological diseases"},{"Tag_Name__c":"Inborn Errors of Metabolism","Tag_Category__c":"Cause;Disease Category","category_description":"Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.","curated_tag_name":"Inherited metabolic diseases"},{"Tag_Name__c":"Mitochondrial","Tag_Category__c":"Account;Cause;Disease Category","category_description":"Mitochondrial diseases are a group of genetic diseases that affect the ability of the body's cells to make energy.","curated_tag_name":"Mitochondrial diseases"},{"Tag_Name__c":"Peripheral Neuropathy","Tag_Category__c":"Account","curated_tag_name":"Peripheral neuropathy"},{"Tag_Name__c":"Epilepsy","Tag_Category__c":"Account;Specialist","curated_tag_name":"Epilepsy"},{"Tag_Name__c":"Neurodevelopmental disabilities","Tag_Category__c":"Specialist","curated_tag_name":"Neurodevelopmental disabilities"},{"Tag_Name__c":"Neuromuscular medicine","Tag_Category__c":"Specialist","curated_tag_name":"Neuromuscular medicine"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:2394"}],"Diagnosis__c":[{"Type__c":"NEWBORN","Category__c":"Other","Curie__c":"http://newbornscreeningcodes.nlm.nih.gov/nb/sc/condition/E3"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0268193"},{"Type__c":"GTR","Curie__c":"MEDGEN:CN043137"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0003263","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK220444","Source__c":"Gene Review","Xref__c":"NBK220444"},{"URL__c":"https://www.orpha.net/en/disease/detail/2394","Source__c":"C5574660; MONDO:0009529","Xref__c":"ORPHA:2394"},{"URL__c":"https://www.omim.org/entry/246900","Source__c":"C5574660; MONDO:0009529; ORPHA:2394","Xref__c":"OMIM:246900"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C5574660","Source__c":"C5574660","Xref__c":"C5574660"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=29914000","Source__c":"C5574660; MONDO:0009529","Xref__c":"29914000"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=1805500","Source__c":"C5574660","Xref__c":"MEDGEN:1805500"},{"URL__c":"https://medlineplus.gov/genetics/condition/dihydrolipoamide-dehydrogenase-deficiency","Source__c":"GARD:0003263","Xref__c":"https://medlineplus.gov/genetics/condition/dihydrolipoamide-dehydrogenase-deficiency"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0009529","Source__c":"GARD:0003263","Xref__c":"MONDO:0009529"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"DLD","GHR_URL__c":"https://medlineplus.gov/genetics/gene/dld","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011968","HPO_Synonym__c":"Decreased oral intake; Feeding difficulties; Feeding problems; Poor feeding","HPO_Name__c":"Feeding difficulties","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Generalized muscular hypotonia (abnormally low muscle tone).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001290","HPO_Synonym__c":"Generalized decreased muscle tone; Generalized muscular hypotonia; Hypotonia, generalized","HPO_Name__c":"Generalized hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Concentration of a branched chain amino acid in the blood above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008344","HPO_Name__c":"Elevated circulating branched chain amino acid concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001399","HPO_Synonym__c":"Hepatic insufficiency; Liver failure","HPO_Name__c":"Hepatic failure","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Head circumference below 2 standard deviations below the mean for age and sex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000252","HPO_Synonym__c":"Abnormally small cranium; Abnormally small skull; Decreased circumference of cranium; Decreased size of cranium; Decreased size of skull; Reduced head circumference; small cranium; Small head circumference","HPO_Name__c":"Microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormality of the cardiac ventricular function.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030872","HPO_Name__c":"Abnormal cardiac ventricular function","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001254","HPO_Synonym__c":"Dullness; Inaction; Inactivity; Languor; Lethargy; Slowness; Torpor","HPO_Name__c":"Lethargy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001250","HPO_Synonym__c":"Epileptic seizure; Seizures","HPO_Name__c":"Seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002151","HPO_Synonym__c":"Increased blood lactate; Increased serum lactate","HPO_Name__c":"Increased circulating lactate concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001257","HPO_Synonym__c":"Involuntary muscle stiffness, contraction, or spasm; Muscle spasticity; Muscular spasticity","HPO_Name__c":"Spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000708","HPO_Synonym__c":"Behavioral abnormality; Behavioral changes; Behavioral disorders; Behavioral disturbances; Behavioral problems; Behavioral symptoms; Behavioral/psychiatric abnormalities; Behavioural symptoms; Behavioural/Psychiatric abnormality; Psychiatric disorders; Psychiatric disturbances","HPO_Name__c":"Atypical behavior","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Concentration of carnitine in the blood circulation below the lower limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003234","HPO_Synonym__c":"Decreased plasma carnitine","HPO_Name__c":"Decreased circulating carnitine concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormality of coagulation associated with an increased risk of thrombosis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100724","HPO_Synonym__c":"Blood hyperviscosity; Thrombophilia","HPO_Name__c":"Hypercoagulability","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007663","HPO_Synonym__c":"Decreased central vision; Decreased clarity of vision; Decreased visual acuity; Poor visual acuity","HPO_Name__c":"Reduced visual acuity","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003128","HPO_Synonym__c":"Hyperlacticacidemia; Increased lactate in body; Lactic acidemia; Lacticacidemia; Lacticacidosis","HPO_Name__c":"Lactic acidosis","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001638","HPO_Synonym__c":"Disease of the heart muscle","HPO_Name__c":"Cardiomyopathy","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Abnormally increased size of the liver.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002240","HPO_Synonym__c":"Enlarged liver","HPO_Name__c":"Hepatomegaly","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Central nervous system dysfunction in association with liver failure and characterized clinically (depending on degree of severity) by lethargy, confusion, nystagmus, decorticate posturing, spasticity, and bilateral Babinski reflexes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002480","HPO_Name__c":"Hepatic encephalopathy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001251","HPO_Synonym__c":"Cerebellar ataxia","HPO_Name__c":"Ataxia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A decreased concentration of glucose in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001943","HPO_Synonym__c":"Hypoglycaemia; Low blood sugar","HPO_Name__c":"Hypoglycemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002013","HPO_Synonym__c":"Emesis; Throwing up; Vomiting","HPO_Name__c":"Vomiting","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A greater than normal concentration of 2-oxoglutaric acid in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012402","HPO_Synonym__c":"Elevated urinary 2-oxoglutarate; Increased urine alpha-ketoglutarate concentration","HPO_Name__c":"Increased urine alpha-ketoglutarate concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An increased concentration of ammonia in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001987","HPO_Synonym__c":"High blood ammonia levels","HPO_Name__c":"Hyperammonemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012758","HPO_Synonym__c":"NDD","HPO_Name__c":"Neurodevelopmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001508","HPO_Synonym__c":"Faltering weight; FTT; Postnatal failure to thrive; Weight faltering","HPO_Name__c":"Failure to thrive","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An increased concentration of isoleucine in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010913","HPO_Synonym__c":"High blood isoleucine concentration","HPO_Name__c":"Hyperisoleucinemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002910","HPO_Synonym__c":"Abnormal liver enzymes; Abnormal liver function; Abnormal liver function tests; Elevated circulating hepatic transaminase activity; Elevated liver enzymes; Elevated serum transaminases; Elevated transaminases; High liver enzymes; Increased liver enzymes; Increased liver function tests; Increased transaminases; Raised liver enzymes; Subclinical abnormal liver function tests","HPO_Name__c":"Elevated circulating hepatic transaminase concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:2394","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Sudden and involuntary contractions of one or more muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003394","HPO_Synonym__c":"Muscle cramps; Muscle spasms","HPO_Name__c":"Muscle spasm","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism","Mitochondrial"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism","Mitochondrial"],"Specialist":["Genetics","Neurology","Epilepsy","Neurodevelopmental disabilities","Neuromuscular medicine","Pediatrics"],"Account":["Mitochondrial","Peripheral Neuropathy","Epilepsy"]},"synonyms":["congenital infantile lactic acidosis due to lad deficiency"," cytochrome-b reductase deficiency"," deficiency of diaphorase"," deficiency of dihydrolipoamide dehydrogenase"," deficiency of lipoamide reductase (nadh)"," diaphorase deficiency"," dihydrolipoamide dehydrogenase (e3) deficiency"," dihydrolipoamide dehydrogenase deficiency"," dihydrolipoamide dehydrogenase e3 deficiency"," dihydrolipoyl dehydrogenase deficiency"," dld - dihydrolipoamide dehydrogenase deficiency"," dld deficiency"," dldd"," e3 deficiency"," e3-deficient maple syrup urine disease"," lactic acidosis due to lad deficiency"," lipoamide dehydrogenase deficiency"," lipoamide dehydrogenase deficiency, lactic acidosis due to"," maple syrup urine disease with lactic acidosis"," maple syrup urine disease, type iii"]}