An infant presents with history of seizures & skin rashes. Investigations show metabolic acidosis increased blood ketone levels and normal NH3. This child is likely to be suffering from –

Correct Answer: Multiple carboxylase deficiency
Description: Ans. is 'd' i.e., Multiple Carboxylase Deficiency In the degradation of valise, leucine, isoleucine (essential, branched chain aminoacids), the intermediate metabolites are all 'organic acids', and deficiency of any of the degradative enzymes (except for transminases) causes acidosis due to accumulation of organic acids before the enzymatic block. Although most clinical manifestation are non specific, some, manifestations may provide impoant clues to the nature of enzyme deficiency. I have below, outlined, an approach to infants with a typical presentation, suspected of having an organic acidemia. COMMONFEATURES Refusal of feed Vomiting Acidosis Dehydration Neutropinia Hypoglycemia o The patient in question has ketosis as well as skin manifestation and thefore the answer is Multiple carboxylase deficiency. o Normal levels of ammonia rule out urea cycle enzyme deficiency. Multiple carboxylase deficiency o Autosomal recessive disorder o Present with breathing difficulty in a baby appearing normal at bih, o Feeding problems, hypotonia. Generalized erythmatous rash with exfoliation and alopecia, failure to thrive, seizure, coma, development delay. o Tomcat urine odour o Lab findings are metabolic acidosis, ketosis, hyperammonemia, o Diagnosis is confirmed by enzyme assay in lymphocytes o Treatment 10 mg/day orally biotin. Biotin is a co-factor for all four carboxylase enzymes ---> acetyl CoA carboxylase, Pyruvate carboxylase, propionyl CoA & methylcrotonyl CoA carboxylase. Early diagnosis and treatment is critical to prevent irreversible neurologic damage.
Category: Pediatrics
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