{"Name":"D,L-2-hydroxyglutaric aciduria","DiseaseID__c":"GARD:0017540","id":17540,"encodedName":"dl-2-hydroxyglutaric-aciduria","IsDeleted":false,"Disease_Name_Full__c":"D,L-2-hydroxyglutaric aciduria","Xref_IDs__c":"713401006; C5574940; DOID:0111619; MEDGEN:1802316; MONDO:0014072; OMIM:615182; ORPHA:356978","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":4,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":0,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":2,"Description_Source__c":"MONDO:0014072","Disease_Description__c":"A rare inborn error of metabolism characterized by severe neonatal epileptic encephalopathy, episodes of apnea and respiratory distress, severe global developmental delay or absent psychomotor development, severe muscular hypotonia or absent voluntary movements, feeding difficulties and failure to thrive, absence of visual contact, abnormal brain morphology (including cerebral atrophy, ventriculomegaly and hypoplasia or dysplasia of the corpus callosum), mild dysmorphic features (frontal bossing, hypertelorism, downslanting palpebral fissures, flat nasal bridge), elevated CSF and plasma lactate and urinary Krebs cycle metabolites.","GARD_Name__c":"D,L-2-hydroxyglutaric aciduria","GARD_Synonym__c":"combined d-2- and l-2-hydroxyglutaric aciduria; combined d-2-hydroxyglutaric acidemia and l-2-hydroxyglutaric acidemia; combined d-2-hydroxyglutaric aciduria and l-2-hydroxyglutaric aciduria; d,l-2-hga; d,l-2-hydroxyglutaric acidemia; d2l2ad","Curated_Disease_Description_Source__c":"ORPHA:356978","Curated_Disease_Description__c":"A rare inborn error of metabolism characterized by severe neonatal epileptic encephalopathy, episodes of apnea and respiratory distress, severe global developmental delay or absent psychomotor development, severe muscular hypotonia or absent voluntary movements, feeding difficulties and failure to thrive, absence of visual contact, abnormal brain morphology (including cerebral atrophy, ventriculomegaly and hypoplasia or dysplasia of the corpus callosum), mild dysmorphic features (frontal bossing, hypertelorism, downslanting palpebral fissures, flat nasal bridge), elevated cerebrospinal fluid (CSF) and plasma lactate and urinary Krebs cycle metabolites.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Newborn and as an Infant","SourceID__c":"ORPHA:356978","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0014072","ORPHANET_ID__c":"ORPHA:356978","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Aciduria d,l-2-hidroxiglutárica","Spanish_Description_Source__c":"ORPHA:356978","Spanish_Description__c":"Es un error innato del metabolismo poco frecuente caracterizado por encefalopatía epiléptica neonatal grave, episodios de apnea y dificultad respiratoria, grave retraso global del desarrollo o ausencia de desarrollo psicomotor, hipotonía muscular grave o ausencia de movimientos voluntarios, dificultades en la alimentación y fallo de medro, contacto visual ausente, morfología cerebral anómala (incluyendo atrofia cerebral, ventriculomegalia e hipoplasia o displasia del cuerpo calloso), características dismórficas leves (frente prominente, hipertelorismo, fisuras palpebrales inclinadas hacia abajo, puente nasal plano) y niveles elevados de lactato en plasma y líquido cefalorraquideo, así como de metabolitos del ciclo de Krebs en orina.","Spanish_Disease_Name__c":"aciduria d,l-2-hidroxiglutárica","Spanish_GARD_Synonym__c":"acidemia d-2-hidroxiglutárica y acidemia l-2-hidroxiglutárica combinada; acidemia d,l-2-hidroxiglutárica; aciduria d-2-hidroxiglutárica y aciduria l-2-hidroxiglutárica combinada; d,l-2-hga","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":"A rare inborn error of metabolism characterized by severe neonatal epileptic encephalopathy, episodes of apnea and respiratory distress, severe global developmental delay or absent psychomotor development, severe muscular hypotonia or absent voluntary movements, feeding difficulties and failure to thrive, absence of visual contact, abnormal brain morphology (including cerebral atrophy, ventriculomegaly and hypoplasia or dysplasia of the corpus callosum), mild dysmorphic features (frontal bossing, hypertelorism, downslanting palpebral fissures, flat nasal bridge), elevated cerebrospinal fluid (CSF) and plasma lactate and urinary Krebs cycle metabolites.","Curated_Disease_Description_Source__c":"ORPHA:356978","GARD_Synonym__c":"combined d-2- and l-2-hydroxyglutaric aciduria; combined d-2-hydroxyglutaric acidemia and l-2-hydroxyglutaric acidemia; combined d-2-hydroxyglutaric aciduria and l-2-hydroxyglutaric aciduria; d,l-2-hga; d,l-2-hydroxyglutaric acidemia; d2l2ad","Name":"D,L-2-hydroxyglutaric aciduria","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"},{"Account_Name__c":"Alex The Leukodystrophy Charity","Website__c":"https://www.alextlc.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":"Epilepsy","Tag_Category__c":"Account;Specialist","curated_tag_name":"Epilepsy"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:356978"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:356978"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=1802316","Source__c":"C5574940","Xref__c":"MEDGEN:1802316"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C5574940","Source__c":"C5574940","Xref__c":"C5574940"},{"URL__c":"https://www.orpha.net/en/disease/detail/356978","Source__c":"C5574940; MONDO:0014072; ORPHA:356978","Xref__c":"ORPHA:356978"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=713401006","Source__c":"C5574940; MONDO:0014072","Xref__c":"713401006"},{"URL__c":"https://www.omim.org/entry/615182","Source__c":"C5574940; MONDO:0014072; ORPHA:356978","Xref__c":"OMIM:615182"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0111619","Source__c":"MONDO:0014072","Xref__c":"DOID:0111619"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0014072","Source__c":"GARD:0017540","Xref__c":"MONDO:0014072"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"SLC25A1","GHR_URL__c":"https://medlineplus.gov/genetics/gene/slc25a1","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001298","HPO_Name__c":"Encephalopathy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000737","HPO_Synonym__c":"Cranky; Easily annoyed; Easily bothered; Easily upset; Grumpy; Hot-temper; Irritability; Irritable; Irritable mood; On edge; Quick-temper; Short fuse; Short tempered","HPO_Name__c":"Irritability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000256","HPO_Synonym__c":"Increased size of cranium; Increased size of skull; Large head; Large head circumference; Macrocephalus; Macrocrania; Megacephaly","HPO_Name__c":"Macrocephaly","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002094","HPO_Synonym__c":"Abnormal breathing; Breathing difficulty; Difficult to breathe; Difficulty breathing; Shortness of breath; Trouble breathing","HPO_Name__c":"Dyspnea","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"Stridor is a high pitched sound resulting from turbulent air flow in the upper airway.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010307","HPO_Name__c":"Stridor","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001321","HPO_Synonym__c":"Congenital cerebellar hypoplasia; Hypoplasia of cerebellum; Hypoplastic cerebellum; Small cerebellum; Underdeveloped cerebellum","HPO_Name__c":"Cerebellar hypoplasia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"The concentration of succinate in the urine, normalized for urine concentration, is above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0033092","HPO_Name__c":"Increased urine succinate level","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increase in the level of L-2-hydroxyglutaric acid in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0040144","HPO_Name__c":"L-2-hydroxyglutaric aciduria","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002093","HPO_Synonym__c":"Respiratory impairment","HPO_Name__c":"Respiratory insufficiency","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","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":"OMIM:615182","Feature__r":{"HPO_Description__c":"Delayed myelination.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012448","HPO_Name__c":"Delayed myelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"An increase in size of the ventricular system of the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002119","HPO_Synonym__c":"Cerebral ventricular dilatation; Dilated cerebral ventricle; Dilated cerebral ventricles; Dilated ventricles; Enlarged cerebral ventricles; Enlarged ventricles; Enlarged ventricular system; Large cerebral ventricles and cisternae; Ventricular dilatation","HPO_Name__c":"Ventriculomegaly","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"The concentration of L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF) is above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:6000509","HPO_Name__c":"Elevated CSF L-2-hydroxyglutaric acid concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"The concentration of D-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF) is above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:6000246","HPO_Name__c":"Elevated CSF D-2-hydroxyglutaric acid concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006829","HPO_Synonym__c":"Hypotonia, severe; Severely decreased muscle tone","HPO_Name__c":"Severe muscular hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100704","HPO_Synonym__c":"Cortical blindness; Cortical visual impairment; Cortical/cerebral visual impairment; CVI","HPO_Name__c":"Cerebral visual impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","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":"OMIM:615182","HPO_Frequency__c":"Occasional (5-29%)","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":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001263","HPO_Synonym__c":"Delayed cognitive development; Delayed development; Delayed developmental milestones; Delayed intellectual development; Delayed milestones; Delayed psychomotor development; Developmental delay; Developmental delay in early childhood; Developmental delay, global; Developmental retardation; GDD; Lack of psychomotor development; Motor and developmental delay; Motormental retardation; Psychomotor delay; Psychomotor development deficiency; Psychomotor development failure; Psychomotor developmental delay; Retarded development; Retarded mental development; Retarded psychomotor development","HPO_Name__c":"Global developmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","Feature__r":{"HPO_Description__c":"A reduced frequency or duration of eye contact.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000817","HPO_Synonym__c":"Poor eye contact","HPO_Name__c":"Reduced eye contact","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","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":"OMIM:615182","HPO_Frequency__c":"Very frequent (80-99%)","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"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism"],"Specialist":["Genetics","Neurology","Epilepsy","Pediatrics"],"Account":["Epilepsy"]},"synonyms":["combined d-2- and l-2-hydroxyglutaric aciduria"," combined d-2-hydroxyglutaric acidemia and l-2-hydroxyglutaric acidemia"," combined d-2-hydroxyglutaric aciduria and l-2-hydroxyglutaric aciduria"," d,l-2-hga"," d,l-2-hydroxyglutaric acidemia"," d2l2ad"]}