3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals.
Orphanet J Rare Dis
; 7: 31, 2012 May 29.
Article
in En
| MEDLINE
| ID: mdl-22642865
ABSTRACT
BACKGROUND:
Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine metabolism caused by mutations in MCCC1 or MCCC2 encoding the α and ß subunit of MCC, respectively. The phenotype is highly variable ranging from acute neonatal onset with fatal outcome to asymptomatic adults.METHODS:
We report clinical, biochemical, enzymatic and mutation data of 88 MCC deficient individuals, 53 identified by newborn screening, 26 diagnosed due to clinical symptoms or positive family history and 9 mothers, identified following the positive newborn screening result of their baby.RESULTS:
Fifty-seven percent of patients were asymptomatic while 43% showed clinical symptoms, many of which were probably not related to MCC deficiency but due to ascertainment bias. However, 12 patients (5 of 53 identified by newborn screening) presented with acute metabolic decompensations. We identified 15 novel MCCC1 and 16 novel MCCC2 mutant alleles. Additionally, we report expression studies on 3 MCCC1 and 8 MCCC2 mutations and show an overview of all 132 MCCC1 and MCCC2 variants known to date.CONCLUSIONS:
Our data confirm that MCC deficiency, despite low penetrance, may lead to a severe clinical phenotype resembling classical organic acidurias. However, neither the genotype nor the biochemical phenotype is helpful in predicting the clinical course.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urea Cycle Disorders, Inborn
Type of study:
Prognostic_studies
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Orphanet J Rare Dis
Journal subject:
MEDICINA
Year:
2012
Document type:
Article
Affiliation country:
Suiza