Related Experiment Videos
Intermittent ataxia and immunodeficiency with multiple carboxylase deficiencies: a biotin-responsive disorder
Abstract:
A small group of inborn errors of metabolism are manifested by intermittent cerebellar ataxia. We have previously reported a family with an inherited metabolic defect resulting in multiple carboxylase deficiencies which were responsive to pharmacological doses of biotin. Affected children presented with a skin rash, infections, acute intermittent ataxia, and lactic acidosis. Two affected siblings died prior to diagnosis and therapy, and a detailed postmortem examination was performed on one of them. The brain was characterized by atrophy restricted to the superior vermis of the cerebellum, a finding strikingly similar to that found in chronic alcoholism. Intermittent ataxia would suggest a potentially treatable metabolic disease, and clinical evaluation should include studies of intermediary metabolism and immune function.
Insights
Inborn errors of metabolism can cause intermittent cerebellar ataxia. This study highlights a biotin-responsive multiple carboxylase deficiency presenting with ataxia and lactic acidosis, emphasizing the need for metabolic evaluation.
Area of Science:
- Biochemistry
- Neurology
- Genetics
Background:
- Inborn errors of metabolism (IEMs) can present with neurological symptoms, including intermittent cerebellar ataxia.
- Multiple carboxylase deficiencies are rare IEMs treatable with biotin supplementation.
- Previous work identified a family with biotin-responsive multiple carboxylase deficiencies.
Observation:
- Affected children exhibited a characteristic rash, recurrent infections, acute intermittent ataxia, and lactic acidosis.
- Postmortem examination of a deceased sibling revealed cerebellar atrophy, specifically in the superior vermis.
- This neuropathological finding resembled changes seen in chronic alcoholism.
Findings:
- The inherited metabolic defect led to multiple carboxylase deficiencies.
- Pharmacological doses of biotin were effective in treating the condition.
- The specific pattern of cerebellar atrophy suggests a link between metabolic dysfunction and neurodegeneration.
Implications:
- Intermittent cerebellar ataxia in children warrants investigation for treatable metabolic disorders.
- Diagnostic workup should include assessment of intermediary metabolism and immune function.
- Early diagnosis and biotin therapy can potentially prevent severe neurological damage and mortality.