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Fatal ataxic encephalopathy and carnitine acetyltransferase deficiency: a functional defect of pyruvate oxidation?

S DiDonato, M Rimoldi, A Moise

    Neurology
    |December 1, 1979
    PubMed

    Insights

    Carnitine acetyltransferase deficiency caused a fatal neurological and liver disorder in a child. This impaired acetyl-CoA utilization in brain mitochondria, leading to severe illness.

    Area of Science:

    • Biochemistry
    • Neurology
    • Metabolic Disorders

    Background:

    • Carnitine acetyltransferase (CrAT) plays a crucial role in fatty acid metabolism and energy production within mitochondria.
    • Defects in mitochondrial enzymes can lead to severe neurological and systemic manifestations.
    • Understanding enzyme deficiencies is key to diagnosing and potentially treating complex pediatric diseases.

    Observation:

    • A pediatric patient presented with a 14-month illness including intermittent ataxia, oculomotor palsy, hypotonia, confusion, and consciousness disturbances.
    • Liver dysfunction was noted in the final 4 months of life.
    • Autopsy and fibroblast studies were performed to investigate potential metabolic causes.

    Findings:

    • Carnitine acetyltransferase (CrAT) activity was deficient in the patient's liver, brain, kidney, and cultured fibroblasts.
    • Activities of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase were normal.
    • Medium- and long-chain carnitine acyltransferase activities were unaffected, suggesting a specific CrAT defect.

    Implications:

    • The findings suggest a functional defect in acetyl-coenzyme A (acetyl-CoA) utilization within brain mitochondria due to CrAT deficiency.
    • This specific enzyme defect may underlie the severe neurological symptoms observed in the patient.
    • Further research into CrAT function and its role in neurodevelopmental disorders is warranted.

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