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Genetic and Rare Diseases Information Center (GARD)

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Pyruvate dehydrogenase deficiency

Other Names for this Disease
  • PDHC
  • Pyruvate dehydrogenase complex deficiency
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What are the signs and symptoms of pyruvate dehydrogenase deficiency?

Pyruvate dehydrogenase (PDH) deficiency can have a significant effect on fetal development, which may become apparent during late pregnancy with poor fetal weight gain and decreasing levels of estriol in the urine of the mother during pregnancy. Delivery may be complicated, and babies may have low Apgar scores. A low birth weight is common. It has been suggested that there is a characteristic abnormal appearance associated with PDH deficiency, which may include a narrow head, prominent forehead (frontal bossing), wide nasal bridge, long philtrum and flared nostrils; however, these are not seen in all individuals and these features may occur with other disorders as well. Other abnormalities that have been reported include a simian crease, short neck, slight shortening of the limbs, flexion contractures (bent fingers), pes cavus (high arched foot), club foot, ventricular septal defect, and hydronephrosis.[1]

Individuals with PDH deficiency typically develop symptoms soon after birth. In general, there are two major types of onset: metabolic and neurological. The metabolic type presents as severe lactic acidosis (too much lactate in the bloodstream). This often does not respond to treatment, thus many of the individuals with this type of onset die during the newborn period (in very few cases, the lactic acidosis has been reported to respond to high doses of thiamine). Some individuals with severe lactic acidosis have also had severe hyperammonemia (high levels of ammonia in the blood). Individuals with the neurological type typically have hypotonia (poor muscle tone), poor feeding, and lethargy, and they later develop seizures. This type typically progresses to severe mental retardation, microcephaly (small head), blindness, and spasticity with secondary contractures (damage to muscles and tendons). However, long term survival is possible and several individuals with this type have reportedly reached their teens. Between these two extremes, there is a continuous range of intermediate forms. When the metabolic abnormalities (lactic acidosis and hyperammonemia) are less severe, the onset may be delayed until later in infancy, and these individuals may have intermittent episodes of lactic acidosis, which often is brought on by an illness and is associated with cerebellar ataxia (abnormal muscle movement). Some of the individuals with primarily neurological symptoms are said to have Leigh's disease.[1]

Although PDH deficiency occurs in males and females equally, the presentation of the disease differs between them. The metabolic type, especially the severe neonatal lactic acidosis, is much more common in males; the chronic, neurological form is much more common in females.[1]
Last updated: 1/4/2011

  1. G K Brown, L J Otero, M LeGris, R M Brown. Pyruvate dehydrogenase deficiency. Journal of Medical Genetics. 1994; 31:875-879. Accessed 1/3/2011.