Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Pyruvate dehydrogenase (PDH) deficiency is a rare metabolic disorder affecting cellular energy production.
• Unusual and intermittent clinical presentations can delay diagnosis.

Observation:

• Two siblings with a novel PDHA1 gene mutation (G585C) exhibited recurrent isolated ataxia in infancy.
• Symptoms initially resolved but progressed to severe encephalopathy, with death in their twenties.
• Normal blood and CSF lactate levels were observed, and no thiamine responsiveness was noted.

Findings:

• A new mutation (G585C) in the PDHA1 gene was identified as the cause of PDH deficiency.
• The mutation, though in the thiamine pyrophosphate binding domain, did not result in thiamine responsiveness.
• The study highlights a spectrum of intermittent neurological symptoms associated with PDH deficiency.

Implications:

• PDH deficiency should be considered in the differential diagnosis of unexplained intermittent neurological symptoms.
• The long-term prognosis for PDH deficiency remains uncertain and requires further investigation.
• Normal CSF lactate levels do not exclude the diagnosis of PDH deficiency.