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Biotin-reversible neurodegenerative disease in infancy
Insights
A rare biotin-responsive regressive brain disease can occur in infants. Early biotin supplementation can reverse severe neurological symptoms and developmental regression, even before metabolic acidosis is evident.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Inborn errors of metabolism can present with severe neurological symptoms in infancy.
- Early diagnosis and intervention are crucial for managing genetic metabolic disorders.
Observation:
- Two siblings presented with myoclonic jerks and developmental regression starting at 5 months of age.
- The younger sibling exhibited metabolic acidosis with elevated organic acids and neurological deterioration, including hyperventilation and decerebrate posturing.
Findings:
- Treatment with biotin (10 mg daily) led to rapid clinical and biochemical improvement within 36 hours.
- Symptoms such as hyperventilation and abnormal organic acid excretion resolved, and neurological function normalized.
- Despite the biochemical response, fibroblast cultures showed normal enzyme levels for beta-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase.
Implications:
- This case highlights a biotin-reversible regressive brain disease that may precede overt metabolic acidosis.
- Clinicians should consider biotin deficiency or dependency in infants with unexplained neurological regression and hyperventilation.
- The findings underscore the importance of prompt clinical assessment and empirical treatment trials in suspected metabolic encephalopathies.
Abstract:
Two siblings with consanguineous parents began having myoclonic jerks at age 5 months after introduction of mixed feeding. There was later developmental regression. The elder girl died without diagnosis aged 1 year, after prolonged continuous hyperventilation. The younger sibling did not have metabolic acidosis when first investigated for myoclonus and hypotonia aged 5 months. At 9.5 months, when intermittently decerebrate and hyperventilating, she had a metabolic acidosis with elevated blood lactic, pyruvic and beta-hydroxybutyric acids, and beta-hydroxyisovaleric aciduria. On the assumption that she had beta-methylcrotonyl-CoA carboxylase deficiency she was started on biotin, 10 mg daily. Within 36 h there was dramatic clinical and biochemical improvement. Previously defective eye movement control and gaze became normal, hyperventilation ceased, and excessive organic acid excretion in urine was abolished. She remains on long-term biotin and at age 2 years her development appears normal in all respects. Fibroblast culture however revealed normal quantities of the enzymes beta-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase. Irrespective of niceties of enzyme and organic acid biochemistry, the clinician must be aware of biotin-reversible regressive brain disease which may present before manifest metabolic acidosis.