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Genetic and Rare Diseases Information Center (GARD)

Pyruvate dehydrogenase deficiency

Other Names for this Disease
  • Pyruvate dehydrogenase complex deficiency
  • PDHC
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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

The Human Phenotype Ontology provides the following list of signs and symptoms for Pyruvate dehydrogenase deficiency. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms.

Signs and Symptoms Approximate number of patients (when available)
Feeding difficulties in infancy 90%
Muscular hypotonia 90%
Reduced consciousness/confusion 90%
Abnormal pattern of respiration 50%
Abnormal pyramidal signs 50%
Abnormality of eye movement 50%
Aplasia/Hypoplasia of the corpus callosum 50%
Chorea 50%
Cognitive impairment 50%
Gait disturbance 50%
Hypertonia 50%
Incoordination 50%
Intrauterine growth retardation 50%
Microcephaly 50%
Neurological speech impairment 50%
Seizures 50%
Tremor 50%
Abnormal facial shape 35%
Abnormality of the nose 7.5%
Abnormality of the palate 7.5%
Cerebral palsy 7.5%
Epicanthus 7.5%
Frontal bossing 7.5%
Hypertelorism 7.5%
Long philtrum 7.5%
Multiple lipomas 7.5%
Narrow face 7.5%
Pectus excavatum 7.5%
Respiratory insufficiency 7.5%
Trigonocephaly 7.5%
Upslanted palpebral fissure 7.5%
Ventriculomegaly 7.5%
Agenesis of corpus callosum -
Anteverted nares -
Apneic episodes precipitated by illness, fatigue, stress -
Basal ganglia cysts -
Cerebral atrophy -
Choreoathetosis -
Chronic lactic acidosis -
Decreased activity of the pyruvate dehydrogenase (PDH) complex -
Dystonia -
Episodic ataxia -
Flared nostrils -
Hyperalaninemia -
Increased CSF lactate -
Increased serum lactate -
Infantile onset -
Intellectual disability -
Lethargy -
Phenotypic variability -
Ptosis -
Severe lactic acidosis -
Small for gestational age -
Wide nasal bridge -
X-linked dominant inheritance -

Last updated: 7/1/2016

The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature.

The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined.

Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.

  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.

Other Names for this Disease
  • Pyruvate dehydrogenase complex deficiency
  • PDHC
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.