“Double Hit” Homozygous Mutations for Two Different Rare Inborn Errors of Metabolism: A Burden for Countries with High Prevalences of Consangineous Marriages

Inborn errors of metabolism comprise a broad range of genetic diseases of which most are inherited in an autosomal recessive manner. Although being rare, there is a significant increase in their rate especially in countries where consanguineous marriages are performed. Isovaleric aciduria is an organic aciduria characterized by abnormal leucine metabolism resulting from a deficiency in the enzyme isovaleryl-CoA dehydrogenase. Niemann-Pick disease Type C is a rare autosomal recessive inherited disorder involving the intracellular transport of endocytosed cholesterol with sequestration of unesterified cholesterol in lysosomes and late endosomes. Both of these disorders are rarely encountered inborn errors of metabolism. We report a case of a boy with marked jaundice and hepatosplenomegaly, who was later diagnosed as isovaleric aciduria and Niemann-Pick disease Type C concomitantly. The diagnoses were proven by genetic analyses. A novel mutation for Niemann-Pick Type C has also been defined in this case report

A rare urea cycle disorder in a neonate: N-acetylglutamate synthetase deficiency

Urea cycle disorders (UCD), are genetically inherited diseases that may have a poor outcome due to to profound hyperammonemia. We report the case of a baby girl diagnosed as N-acetylglutamate synthase (NAGS) deficiency. The patient was evaluated due to diminished sucking and hypotonicity. Physical examination showed hepatomegaly. Complete blood count, biochemical values and blood gas analyses were normal, acute phase reactants were negative. Further laboratory analyses showed no ketones in blood and highly elevated ammonia. Metabolic tests were inconclusive. Emergency treatment was initiated immediately and she was discharged on the 15th day of admission. NAGS deficiency was confirmed by DNA-analysis. She is now without any dietary restriction or other medication, except N-carbamylglutamate (NCG). NAGS deficiency is the only UCD which can be specifically and effectively treated by NCG. Early recognition of disease will lead to early treatment that may prohibit devastating effects of hyperammonemia