Pyruvate Dehydrogenase E1-Alpha Deficiency (PDHAD)

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Disease Ontology 12 DOID:3649 OMIM 57 312170 PS312170 KEGG 37 H00072 H01997 MeSH 44 D015325 NCIt 50 C103968 SNOMED-CT 68 46683007 ICD10 33 E74.4

MESH via Orphanet 45 C536257 D015325 ICD10 via Orphanet 34 E74.4 UMLS via Orphanet 73 C0034345 C1839413 C2936911 Orphanet 59 ORPHA765 ORPHA79243 MedGen 42 C0034345 C1839413 C1839414 C1839885 more EFO 17 EFO_0007459 UMLS 72 C0034345 C1839413

NIH Rare Diseases : ⁵³ 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 (mutations 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. Treatment for PDC deficiency includes dietary supplementation with carnitine, thiamine, and lipoic acid.

MalaCards based summary : Pyruvate Dehydrogenase E1-Alpha Deficiency, also known as pyruvate dehydrogenase complex deficiency, is related to lactic acidosis and pyruvate dehydrogenase e3-binding protein deficiency, and has symptoms including seizures, lethargy and nasal flaring. An important gene associated with Pyruvate Dehydrogenase E1-Alpha Deficiency is PDHA1 (Pyruvate Dehydrogenase E1 Alpha 1 Subunit), and among its related pathways/superpathways are Pyruvate metabolism and Glycolysis / Gluconeogenesis. The drugs Strawberry and pyruvate have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and eye, and related phenotypes are muscular hypotonia and feeding difficulties in infancy

Disease Ontology : ¹² A carbohydrate metabolic disorder characterized by the buildup of lactic acid in the body and a variety of neurological problems and caused by a deficiency of one of the three enzymes in the pyruvate dehydrogenase complex.

Genetics Home Reference : ²⁵ Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.

OMIM : ⁵⁷ Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). (312170)

KEGG : ³⁷ Pyruvate dehydrogenase complex deficiency is an autosomal or X-linked recessive disorder caused by deficient enzyme activity in the pyruvate dehydrogenase complex, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. This deficiency in newborns may lead to brain malformations. The PDH complex comprises three catalytic subunits, PDH (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3), and two regulatory subunits, E1 kinase and phospho-E1-phosphatase, together with a sixth component, E3-binding protein, which is believed to play a role in the attachment of E3 to the E2 core.

UniProtKB/Swiss-Prot : ⁷⁴ Pyruvate dehydrogenase E1-alpha deficiency: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.

Wikipedia : ⁷⁵ Pyruvate dehydrogenase deficiency (also known as pyruvate dehydrogenase complex deficiency or PDCD) is... more...

Clinical features from OMIM:

312170

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