Outcome of infants diagnosed with 3-methyl-crotonyl-CoA-carboxylase deficiency by newborn screening.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Georgianne L
GL
Arnold
Denise
D
Salazar
Julie A
JA
Neidich
Pim
P
Suwannarat
Brett H
BH
Graham
Uta
U
Lichter-Konecki
Annet M
AM
Bosch
Kristina
K
Cusmano-Ozog
Greg
G
Enns
Erica L
EL
Wright
Brendan C
BC
Lanpher
Natalie N
NN
Owen
Mark H
MH
Lipson
Roberto
R
Cerone
Paul
P
Levy
Lee-Jun C
LJ
Wong
Antal
A
Dezsofi
D000293:Adolescent; D019735:Carbon-Carbon Ligases / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis* / Q000201:enzymology
D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase