An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening

Abstract 3-Methylcrotonyl-CoA carboxylase (3-MCC) deficiency is an autosomal recessively inherited disease of leucine catabolism. It is the most commonly observed organic acidemia where tandem mass spectrometry can be performed in newborn screening. The clinical phenotypes may differ from neurological involvement in newborns to asymptomatic adults. Diagnosis is made by increased 3-hydroxyisovaleric acid in blood and 3-methylcrotonylglycine in urine. We would like to present an interesting case of a 32-year-old asymptomatic mother, who was investigated metabolically and diagnosed with 3-MCC deficiency, after a 7-day-old healthy baby referred to our unit with the preliminary diagnosis of organic academia during her extended newborn screening. All of the metabolic findings of the baby were normal except for very low carnitine levels. Her mother’s total and free carnitine levels were also extremely low. Urine organic acid analysis revealed excessively increased 3-methylcrotonylglycine and 3-hydroxyisovaleric acid. Acylcarnitine profile showed markedly elevated C5 hydroxy 3 hydroxyisovalerylcarnitine and decreased C2 acetylcarnitine. In order to confirm the diagnosis of 3-methylcrotonylglycinuria, molecular analysis was done, and IVS3-1G>C/p.T556I compound heterozygote mutation was detected. p.T556I is a novel mutation. We would like to emphasize performing extended metabolic investigations in case of suspicion of metabolic disease in order to diagnose metabolic diseases both in babies and in asymptomatic mothers.