ABOUT OUR DISEASE

Learn more about Pyruvate Dehydrogenase Complex Deficiency

Pyruvate Dehydrogenase Complex Deficiency is a disorder of carbohydrate metabolism caused by a deficiency of one of the three enzymes in the pyruvate dehydrogenase complex (PDC). The age of onset and severity of disease symptoms vary widely. 82-88% of cases are due to mutations in the X-linked PDHA1 gene. About 5% due to other primary-specific genes: PDHB, DLAT, PDPA, E3BP (PDHX)1. PDCD can cause profound physical and neurological disabilities. Some clinical features2 include:

  • Hypotonia (53-89%)
  • Developmental delay (69-83%)
  • Ventriculomegaly (35-85%)
  • Corpus callosum abnormalities (15-55%)
  • Seizures (16-57%)
  • Leigh syndrome (12-35%)
  • Ataxia (17-22%)

Females have better survival but surviving females are more severely affected than males. Survival: about 40% die < 3 mo, 60% die < 1 yo, 90% < 4 yo1. Ketogenic diet (KD) has been shown to have a positive affect in the areas of: Epilepsy (decreasing seizures), ataxia, sleep disturbance, speed/language development, social functioning, frequency of hospitalizations, and survival1 2.

It’s important to remember that the clinical presentation and symptoms of PDCD can vary widely and not all patients will have the same symptoms.

References

  1. Shin et al. (2017) Mol Genet Metab, 122:61-66

  2. DeBrosse et al. (2012) Mol Genet Metab, 17:394

    It should be noted that the clinical presentation of PDC deficiency is variable and ranges from fatal congenital lactic acidosis and congenital brain abnormalities to relatively mild ataxia or neuropathy with normal cognitive function and long survival