Outcomes of cases with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency - Report from the Inborn Errors of Metabolism Information System

Abstract

Introduction 3-Methyl crotonyl CoA carboxylase (3MCC) deficiency is an inborn error of leucine metabolism whose detection was increased with the advent of expanded newborn screening. While most NBS-identified infants appear clinically normal, prior studies suggest a possible increased risk for developmental or metabolic abnormalities. As yet, no predictive markers are known that can identify children at risk for biochemical or developmental abnormalities. Method All available 3-MCC cases diagnosed by newborn screening in the Inborn Errors of Metabolism Information System (IBEM-IS) were reviewed for markers that might be predictive of outcome. Results A limited number of cases were identified with traditional biochemical symptoms including acidosis, hyperammonemia or lactic acidosis, and 15% of those with available developmental information had recorded developmental disabilities not clearly attributable to other causes. There was no correlation between newborn screening (NBS) C5OH level and presence of metabolic, newborn, later-life or developmental abnormalities in these cases. Discussion This sample, obtained from the IBEM-IS database, attempts to avoid some of the ascertainment bias present in retrospective studies. An increase in developmental abnormalities and in traditionally described metabolic symptoms remains apparent, although no specific biochemical markers appear predictive of outcome. The role that prevention of fasting plays in outcome cannot be ascertained. These data suggest that C5OH level found on newborn screening by itself is not sufficient for diagnostic or predictive purposes.

Biochemical and molecular characterization of 3-Methylcrotonylglycinuria in an Italian asymptomatic girl

“…, 2009 ). In addition, a recent study pointed out that the C5-OH level found in newborn screening is not sufficient for diagnostic or predictive purposes ( Forsyth et al. , 2016 ).…”

“…The clinical phenotype of 3-MCC deficiency is highly variable, ranging from severe neurological abnormalities and death in infancy ( Baykal et al , 2005 ) to asymptomatic adults ( Dantas et al , 2005 ; Forsyth et al , 2016 ). A severe presentation of 3-MCC deficit may include the Reye-like illness, ketoacidosis, hypoglycemia, hyperammonemia, psychomotor retardation, seizures, symptoms of cardiorespiratory failure and coma.…”

“…Moreover, cardiomyopathy, brain atrophy and fatty infiltration of liver or muscle may also occur ( Grünert et al , 2012 ). Nonetheless, most of the patients diagnosed by NBS as affected by 3-MCC deficiency appear to be asymptomatic during the whole life ( Forsyth et al , 2016 ).…”

Perinatal free carnitine and short chain acylcarnitine blood concentrations in 12,000 full-term breastfed newborns in relation to their birth weight

“…Asymptomatic mothers with 3-methylcrotonyl glycinuria have been identified by detection of abnormal neonatal screening performed in their healthy offspring, having passed the abnormal metabolites to their infants through the placenta. 29 In case of normal mother's results, biotin and especially biotinidase activity in DBS should be performed. 30 Here, we may underline that biotin blood levels were not measured, whereas biotinidase activities were normal in neonates (unpublished data).…”

Long-term follow-up in newborn screening: the role of collaboration

“…A report describing the use of the IBEM-IS to illustrate the outcomes of children with 3-methylcrotonyl-CoA carboxylase deficiency was recently published. 3 The IBEM-IS database was also used to describe outcomes and genotype-phenotype correlations of individuals with very-long-chain acyl-CoA dehydrogenase deficiency. 4 These are just the beginning; the potential of IBEM-IS to inform NBS practices is substantial.…”