Challenges in diagnosing a metabolic disorder: error of pyruvate metabolism or drug induced?

Certain drugs are known to cause metabolic changes resulting in altered metabolic profiles. We report here a case where a combination of antiepileptic drugs resulted in a profile that mimicked a metabolic disorder. A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. Suspecting that the observed metabolic changes could have also arised from medication, current medication was weaned off and replaced with levetiracetam, clonazepam, and levocarnitine (supportive therapy). Metabolic profiling conducted after 47 days showed normal alanine, branched-chain amino acids, ornithine, and lactate-pyruvate ratio, suggesting that the earlier abnormalities could have been medication induced. We stress that metabolic changes resulting from chronic medication should be considered while interpreting a positive result when investigating an inherited metabolic disorder.

Prenatal dolichocephaly: sign of trouble? -A variant of Miller-Dieker syndrome.

Neuroimaging and molecular cytogenetics were used to ascertain the cause of disability in a case. The case was diagnosed to be a variant of Miller-Dieker syndrome (MDS). Retrospective analysis showed a prenatal scan reporting dolichocephaly. We evaluated dolichocephaly, the name associated with a nonsynostotic cause to be a physiological variant having no prognostic value, to that of a similar synostotic or secondary to a neurological disorder cause, with prognostic significance. The report confirmed early craniosynostosis in cases suspected with a neurological disorder and also on an important criterion in molecular testing strategy in cases suspected with MDS.