Microcephaly and a normal head size PDCD is generally presented in one of two forms. The metabolic form appears as lactic acidosis. The neurological form of PDCD contributes to hypotonia, poor feeding, lethargy and structural abnormalities in the brain. Patients may develop seizures and/or neuropathological spasms. These presentations of the disease usually progress to mental retardation, microcephaly, blindness, and spasticity. Females with residual pyruvate dehydrogenase activity will have no uncontrollable systemic lactic acidosis and few, if any, neurological symptoms. Conversely, females with little to no enzyme activity will have major structural brain abnormalities and atrophy. Males with mutations that abolish, or almost abolish, enzyme activity presumably die in utero because brain cells are not able to generate enough ATP to be functionally viable. It is expected that most cases will be of mild severity and have a clinical presentation involving lactic acidosis. Male infants that reach full term display more severe symptoms than females, and exhibit high mortality within the first few years of life Prenatal onset may present with non-specific signs such as low Apgar scores and small for gestational age. These cases display hydrocephalus, and thinning of the cerebral tissue. Metabolic disturbances may also be considered with poor feeding and lethargy out of proportion to a mild viral illness, and especially after bacterial infection has been ruled out.<unk>  activity may be enhanced by exercise, phenylbutyrate and dichloroacetate. The clinical presentation of congenital<unk><unk>  is typically characterized by heterogenous neurological features that usually appear within the first year of life. In addition, patients usually show severe hyperventillation due to profound metabolic acidosis mostly related to lactic acidosis. Metabolic acidosis in these patients is usually refractory to correction with bicarbonate. The following table lists common symptoms of<unk> . + Symptoms Definition/Explanation Lactic Acidosis High levels of lactate in the blood; can cause nausea, vomiting, breathing problems, abnormal heartbeats In less severe cases, signs of lactic acidosis can include ataxia and episodes may only occur when ill, under stress, or after consuming high amounts of carbohydrates. Hyperammonemia High levels of ammonia in the blood; can cause confusion, weakness, fatigue Facial Deformities Narrow head, prominent forehead, wide nasal bridge, flared nostrils Neurological Impairments Developmental delays, intellectual impairments, seizures, lethargy (lack of energy), abnormal eye movements, blindness, microcephaly, poor coordination, difficulty walking Abnormal Brain Structure Underdeveloped corpus callosum, atrophy of the cerebral cortex, lesions on some parts of the brain Muscular Abnormalities Hypotonia (weak muscle tone), spasticity (tight muscles), ataxia (abnormal muscle movements) Abnormalities at Infancy Low APGAR scores (scores measuring a baby's health after birth), low birth weight, difficulty nursing Breathing Difficulties Tachypnea (rapid breathing) Fetal Abnormalities Poor fetal weight gain, low levels of estriol in the mother's urine
Pyruvate dehydrogenase deficiency
Glutaminase deficiency
Pyruvate carboxylase deficiency
Pyruvate kinase deficiency
3-Methylcrotonyl-CoA carboxylase deficiency
Malonyl-CoA decarboxylase deficiency
2-Methylbutyryl-CoA dehydrogenase deficiency
D-glycerate dehydrogenase deficiency