{"Name":"Pyruvate dehydrogenase complex deficiency","DiseaseID__c":"GARD:0007513","id":7513,"encodedName":"pyruvate-dehydrogenase-complex-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Pyruvate dehydrogenase complex deficiency","Xref_IDs__c":"46683007; C0034345; C103968; DOID:3649; MEDGEN:19610; MONDO:0019169; OMIMPS:312170; ORPHA:765","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":2,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":2,"No_of_Disease_Descriptions__c":3,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":3,"Description_Source__c":"MONDO:0019169","Disease_Description__c":"Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency (see these terms).","GARD_Name__c":"Pyruvate dehydrogenase complex deficiency","GARD_Synonym__c":"ataxia with lactic acidosis; ataxia with lactic acidosis 1; ataxia with lactic acidosis i; deficiency of alpha-carboxylase; deficiency of alpha-ketoacid carboxylase; deficiency of pyruvate decarboxylase; deficiency of pyruvate dehydrogenase (cytochrome); deficiency of pyruvic decarboxylase; deficiency of pyruvic dehydrogenase; pdh; pdh - pyruvate dehydrogenase deficiency; pdh deficiency; pdhc; pyruvate decarboxylase deficiency; pyruvate dehydrogenase complex deficiency disease; pyruvate dehydrogenase deficiency","Curated_Disease_Description_Source__c":"GARD:0007513","Curated_Disease_Description__c":"Pyruvate dehydrogenase complex (PDC) deficiency is a type of metabolic disease. This means that the body is not able to efficiently break down nutrients in food to be used for energy. Symptoms of PDC deficiency include signs of metabolic dysfunction such as extreme tiredness (lethargy), poor feeding, and rapid breathing (tachypnea). Other symptoms may include signs of neurological dysfunction such as developmental delay, periods of uncontrolled movements (ataxia), low muscle tone (hypotonia), abnormal eye movements, and seizures. Symptoms usually begin in infancy, but signs can first appear at birth or later in childhood. Symptoms may be especially apparent during times of illness, stress, or after meals with high amounts of carbohydrates. The most common form of PDC deficiency is caused by genetic changes (genetic changes or pathogenic variants) in the PDHA1 gene. These pathogenic variants are inherited in an X-linked manner. Pathogenic variants in other genes including PDHB, DLAT, PDHX, DLD, and PDP1 can also cause PDC deficiency. These pathogenic variants are inherited in an autosomal recessive manner. PDC deficiency is diagnosed based on laboratory tests including blood tests, analysis of the urine, and brain MRI. The diagnosis can be confirmed by analyzing the pyruvate dehydrogenase enzyme.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"from Birth to Childhood","SourceID__c":"ORPHA:765","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0019169","ORPHANET_ID__c":"ORPHA:765","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Deficiencia de piruvato deshidrogenasa","Spanish_Description_Source__c":"ORPHA:765","Spanish_Description__c":"El déficit de piruvato deshidrogenasa (PDHD) es un trastorno neurometabólico raro caracterizado por un amplio rango de signos clínicos con componentes metabólicos y neurológicos de gravedad variable. Las manifestaciones van desde una acidosis láctica neonatal, grave, a menudo letal, a trastornos neurológicos de aparición más tardía. Se han identificado 6 subtipos asociados a la subunidad del complejo PDH afectada con un solapamiento clínico significativo: PDHD por déficit de E1-alfa, E1-beta, E2 y E3, PDHD por déficit de la proteína de unión E3, y déficit de PDH fosfatasa.","Spanish_Disease_Name__c":"deficiencia de piruvato deshidrogenasa","Spanish_GARD_Synonym__c":"deficiencia del complejo piruvato deshidrogenasa; pdh; pdhc","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":"Pyruvate dehydrogenase complex (PDC) deficiency is a type of metabolic disease. This means that the body is not able to efficiently break down nutrients in food to be used for energy. Symptoms of PDC deficiency include signs of metabolic dysfunction such as extreme tiredness (lethargy), poor feeding, and rapid breathing (tachypnea). Other symptoms may include signs of neurological dysfunction such as developmental delay, periods of uncontrolled movements (ataxia), low muscle tone (hypotonia), abnormal eye movements, and seizures. Symptoms usually begin in infancy, but signs can first appear at birth or later in childhood. Symptoms may be especially apparent during times of illness, stress, or after meals with high amounts of carbohydrates. The most common form of PDC deficiency is caused by genetic changes (genetic changes or pathogenic variants) in the PDHA1 gene. These pathogenic variants are inherited in an X-linked manner. Pathogenic variants in other genes including PDHB, DLAT, PDHX, DLD, and PDP1 can also cause PDC deficiency. These pathogenic variants are inherited in an autosomal recessive manner. PDC deficiency is diagnosed based on laboratory tests including blood tests, analysis of the urine, and brain MRI. The diagnosis can be confirmed by analyzing the pyruvate dehydrogenase enzyme.","Curated_Disease_Description_Source__c":"GARD:0007513","GARD_Synonym__c":"ataxia with lactic acidosis; ataxia with lactic acidosis 1; ataxia with lactic acidosis i; deficiency of alpha-carboxylase; deficiency of alpha-ketoacid carboxylase; deficiency of pyruvate decarboxylase; deficiency of pyruvate dehydrogenase (cytochrome); deficiency of pyruvic decarboxylase; deficiency of pyruvic dehydrogenase; pdh; pdh - pyruvate dehydrogenase deficiency; pdh deficiency; pdhc; pyruvate decarboxylase deficiency; pyruvate dehydrogenase complex deficiency disease; pyruvate dehydrogenase deficiency","Name":"Pyruvate dehydrogenase complex deficiency","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Hope for PDCD","Website__c":"https://www.hopeforpdcd.org/"},{"Account_Name__c":"Childhood Dementia Initiative","Website__c":"https://www.childhooddementia.org/"},{"Account_Name__c":"MitoAction","Website__c":"https://www.mitoaction.org/"},{"Account_Name__c":"Metabolic Support UK","Website__c":"https://www.metabolicsupportuk.org"},{"Account_Name__c":"United Mitochondrial Disease Foundation","Website__c":"https://www.umdf.org"},{"Account_Name__c":"Epilepsy Foundation","Website__c":"https://www.epilepsy.com/"}],"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:765"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:765"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:765"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C0034345"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK571223","Source__c":"Gene Review","Xref__c":"NBK571223"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=46683007","Source__c":"C0034345; MONDO:0019169","Xref__c":"46683007"},{"URL__c":"https://www.orpha.net/en/disease/detail/765","Source__c":"C0034345; MONDO:0019169; ORPHA:765","Xref__c":"ORPHA:765"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C0034345","Source__c":"C0034345","Xref__c":"C0034345"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C103968","Source__c":"C0034345; MONDO:0019169","Xref__c":"C103968"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=19610","Source__c":"C0034345","Xref__c":"MEDGEN:19610"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A3649","Source__c":"MONDO:0019169","Xref__c":"DOID:3649"},{"URL__c":"https://www.omim.org/phenotypicSeries/PS312170","Source__c":"MONDO:0019169","Xref__c":"OMIMPS:312170"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0019169","Source__c":"GARD:0007513","Xref__c":"MONDO:0019169"},{"URL__c":"https://medlineplus.gov/genetics/condition/pyruvate-dehydrogenase-deficiency","Source__c":"GARD:0007513","Xref__c":"https://medlineplus.gov/genetics/condition/pyruvate-dehydrogenase-deficiency"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=124593001","Source__c":"C0034345","Xref__c":"124593001"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C015325","Source__c":"C0034345","Xref__c":"D015325"},{"URL__c":"https://www.umdf.org/pdcd-fda-listening-session-report-now-available/"}],"Inheritance__c":["Autosomal recessive","X-linked dominant"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A deficiency or slowing down of growth pre- and postnatally.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001510","HPO_Synonym__c":"Delayed growth; Growth deficiency; Growth delay; Growth failure; Growth retardation; Poor growth; Retarded growth","HPO_Name__c":"Growth delay","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","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":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000582","HPO_Synonym__c":"Mongoloid slant; Upslanting palpebral fissures; Upward slanted palpebral fissures; Upward slanting of palpebral fissures; Upward slanting of the opening between the eyelids; Upward slanting palpebral fissures","HPO_Name__c":"Upslanted palpebral fissure","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001511","HPO_Synonym__c":"Fetal growth restriction; FGR; In utero growth retardation; Intrauterine growth failure; Intrauterine growth restriction; Intrauterine growth retardation, IUGR; Intrauterine retardation; IUGR; Prenatal growth deficiency; Prenatal growth failure; Prenatal growth retardation; Prenatal onset growth retardation; Prenatal-onset growth retardation; Small for gestational age infant","HPO_Name__c":"Intrauterine growth retardation","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","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:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormality in voluntary or involuntary eye movements or their control.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000496","HPO_Synonym__c":"Abnormal extraocular movement; Abnormal extraocular movements; Abnormal eye motility; Abnormal eye movement; Abnormal eye movements; Abnormal motility of the globe of the eye; Abnormal movement of the globe of the eye; Abnormal ocular movements; Abnormality of eye movement; Eye movement abnormalities; Eye movement issue; Ocular movement abnormalities; Oculomotor abnormalities","HPO_Name__c":"Abnormality of eye movement","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","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":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002007","HPO_Synonym__c":"Frontal protuberance; Skull bossing","HPO_Name__c":"Frontal bossing","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000316","HPO_Synonym__c":"Excessive orbital separation; Increased distance between eye sockets; Increased distance between eyes; Increased interpupillary distance; Ocular hypertelorism; Wide-set eyes; Widely spaced eyes; Widened interpupillary distance","HPO_Name__c":"Hypertelorism","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001260","HPO_Synonym__c":"Difficulty articulating speech; Dysarthric speech","HPO_Name__c":"Dysarthria","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000243","HPO_Synonym__c":"Triangular cranium shape; Triangular skull shape; Wedge shaped cranium; Wedge shaped skull","HPO_Name__c":"Trigonocephaly","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Functional neurological abnormalities related to dysfunction of the pyramidal tract.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007256","HPO_Synonym__c":"Corticospinal signs; Pyramidal signs; Pyramidal tract signs","HPO_Name__c":"Abnormal pyramidal sign","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","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":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Very rapid breathing.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002789","HPO_Synonym__c":"Increased respiratory rate or depth of breathing; Polypnea","HPO_Name__c":"Tachypnea","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001332","HPO_Synonym__c":"Dystonic movements","HPO_Name__c":"Dystonia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100021","HPO_Synonym__c":"Cerebral paralysis; CP","HPO_Name__c":"Cerebral palsy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","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:765","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008872","HPO_Name__c":"Feeding difficulties in infancy","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100453","HPO_Name__c":"Osteolytic defects of the middle phalanx of the 4th toe","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000343","HPO_Synonym__c":"Elongated philtrum; Increased height of philtrum; Increased length of philtrum; Increased vertical dimension of philtrum; Vertical hyperplasia of philtrum","HPO_Name__c":"Long philtrum","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Absence or underdevelopment of the corpus callosum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007370","HPO_Synonym__c":"Absent/hypoplastic corpus callosum; Agenesis/hypoplastic corpus callosum; Complete or partial absence of the corpus callosum; Hypoplasia or absence of the corpus callosum; Hypoplastic or absent corpus callosum","HPO_Name__c":"Aplasia/Hypoplasia of the corpus callosum","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","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:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001266","HPO_Synonym__c":"Choreoathetoid movements","HPO_Name__c":"Choreoathetosis","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Very frequent (80-99%)","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:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The term gait disturbance can refer to any disruption of the ability to walk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001288","HPO_Synonym__c":"Abnormal gait; Abnormal walk; Difficulty in walking; Gait abnormalities; Gait difficulties; Gait disturbances; Impaired gait; Walking disability","HPO_Name__c":"Gait disturbance","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","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:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000218","HPO_Synonym__c":"Elevated palate; High arched palate; High palate; High, arched palate; High-arched palate; Increased palatal height; Palate high-arched; Palate, high-arched","HPO_Name__c":"High palate","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An abnormal morphology (form) of the face or its components.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001999","HPO_Synonym__c":"Abnormal facial shape; Abnormal morphology of the face; Distinctive facies; Dysmorphic facial features; Dysmorphic facies; Facial dysmorphism; Unusual facial appearance; Unusual facies","HPO_Name__c":"Abnormal facial shape","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000275","HPO_Synonym__c":"Decreased breadth of face; Decreased horizontal dimension of face; Decreased transverse dimension of face; Decreased width of face; Horizontal deficiency of face; Horizontal hypoplasia of face; Horizontal insufficiency of face; Narrow face; Narrow facies; Thin facies; Transverse deficiency of face; Transverse hypoplasia of face; Transverse insufficiency of face","HPO_Name__c":"Narrow face","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A defect of the chest wall characterized by a depression of the sternum, giving the chest (\\\"pectus\\\") a caved-in (\\\"excavatum\\\") appearance.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000767","HPO_Synonym__c":"Funnel chest","HPO_Name__c":"Pectus excavatum","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Increased breadth of the nasal bridge (and with it, the nasal root).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000431","HPO_Synonym__c":"Broad nasal bridge; Broad nasal root; Broadened nasal bridge; Increased breadth of bridge of nose; Increased breadth of nasal bridge; Increased width of bridge of nose; Increased width of nasal bridge; Nasal bridge broad; Nasal bridge, wide; Wide bridge of nose; Wide nasal bridge; Widened nasal bridge","HPO_Name__c":"Wide nasal bridge","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000286","HPO_Synonym__c":"Epicanthal fold; Epicanthal folds; Epicanthic folds; Eye folds; Palpebronasal fold; Plica palpebronasalis; Prominent eye folds","HPO_Name__c":"Epicanthus","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of multiple lipomas (a type of benign tissue made of fatty tissue).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001012","HPO_Synonym__c":"Lipomata; Multiple fatty lumps","HPO_Name__c":"Multiple lipomas","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:765","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An unintentional, oscillating to-and-fro muscle movement about a joint axis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001337","HPO_Synonym__c":"Tremor; Tremors","HPO_Name__c":"Tremor","Feature_System__c":"Nervous 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":["ataxia with lactic acidosis"," ataxia with lactic acidosis 1"," ataxia with lactic acidosis i"," deficiency of alpha-carboxylase"," deficiency of alpha-ketoacid carboxylase"," deficiency of pyruvate decarboxylase"," deficiency of pyruvate dehydrogenase (cytochrome)"," deficiency of pyruvic decarboxylase"," deficiency of pyruvic dehydrogenase"," pdh"," pdh - pyruvate dehydrogenase deficiency"," pdh deficiency"," pdhc"," pyruvate decarboxylase deficiency"," pyruvate dehydrogenase complex deficiency disease"," pyruvate dehydrogenase deficiency"]}