TY - JOUR
T1 - Outcome of infants diagnosed with 3-methyl-crotonyl-CoA-carboxylase deficiency by newborn screening
AU - Arnold, Georgianne L.
AU - Salazar, Denise
AU - Neidich, Julie A.
AU - Suwannarat, Pim
AU - Graham, Brett H.
AU - Lichter-Konecki, Uta
AU - Bosch, Annet M.
AU - Cusmano-Ozog, Kristina
AU - Enns, Greg
AU - Wright, Erica L.
AU - Lanpher, Brendan C.
AU - Owen, Natalie N.
AU - Lipson, Mark H.
AU - Cerone, Roberto
AU - Levy, Paul
AU - Wong, Lee Jun C.
AU - Dezsofi, Antal
PY - 2012/8
Y1 - 2012/8
N2 - Introduction: 3-Methyl CoA carboxylase (3-MCC) deficiency is an inborn error of metabolism in the catabolism of the amino acid leucine. Original reports suggested this disorder was associated with significant neurological and biochemical effects. However newborn screening has identified a higher than expected incidence of this disorder with apparent normal outcome in most cases. Method: A retrospective analysis of thirty-five cases of 3-MCC deficiency identified by newborn screening and diagnosed by enzyme or molecular analysis. Results: There was a strong inverse correlation between initial C5OH level and residual enzyme activity. A few reports of hypoglycemia, ketosis, poor feeding/failure to thrive or fasting intolerance were reported, but there was no clear relationship between symptoms and residual enzyme activity. Developmental outcome included several children with mental retardation (including one with Down syndrome and one with schizencephaly) and two with Autism Spectrum disorders but there was no apparent relationship to residual enzyme activity. Free carnitine deficiency was relatively common. Discussion: Although residual enzyme activity was clearly related to metabolite elevation, there was no apparent relationship with other measures of outcome. The number of reports of neurologic abnormalities or metabolic symptoms (poor feeding, hypoglycemia, fasting intolerance, etc.) is concerning, but the significance is unclear in this retrospective sample.
AB - Introduction: 3-Methyl CoA carboxylase (3-MCC) deficiency is an inborn error of metabolism in the catabolism of the amino acid leucine. Original reports suggested this disorder was associated with significant neurological and biochemical effects. However newborn screening has identified a higher than expected incidence of this disorder with apparent normal outcome in most cases. Method: A retrospective analysis of thirty-five cases of 3-MCC deficiency identified by newborn screening and diagnosed by enzyme or molecular analysis. Results: There was a strong inverse correlation between initial C5OH level and residual enzyme activity. A few reports of hypoglycemia, ketosis, poor feeding/failure to thrive or fasting intolerance were reported, but there was no clear relationship between symptoms and residual enzyme activity. Developmental outcome included several children with mental retardation (including one with Down syndrome and one with schizencephaly) and two with Autism Spectrum disorders but there was no apparent relationship to residual enzyme activity. Free carnitine deficiency was relatively common. Discussion: Although residual enzyme activity was clearly related to metabolite elevation, there was no apparent relationship with other measures of outcome. The number of reports of neurologic abnormalities or metabolic symptoms (poor feeding, hypoglycemia, fasting intolerance, etc.) is concerning, but the significance is unclear in this retrospective sample.
KW - 3-Methylcrotonyl CoA carboxylase deficiency
KW - Newborn screening
KW - Organic acidemia
UR - http://www.scopus.com/inward/record.url?scp=84864328240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864328240&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2012.04.006
DO - 10.1016/j.ymgme.2012.04.006
M3 - Article
C2 - 22658692
AN - SCOPUS:84864328240
SN - 1096-7192
VL - 106
SP - 439
EP - 441
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 4
ER -