current
CPT2:c.1883A>C (p.Tyr628Ser) AND Carnitine palmitoyltransferase II deficiency, infantile
current
classified by single submitter
Pathogenic
germline
human
not provided
curation
In an infant with the infantile form of CPT II deficiency (600649) originally reported by Demaugre et al. (1991), Bonnefont et al. (1996) identified a homozygous 2399A-C transversion in the CPT2 gene, resulting in a tyr628-to-ser (Y628S) substitution. In vitro functional analysis in fibroblasts showed that the Y628S mutation resulted in 10% CPT II residual activity and markedly impaired oxidation of long-chain fatty acids, whereas the S113L (600650.0002) mutation found in the less severe adult form of the disorder (255110) resulted in 20% CPT II residual activity, without consequence on LCFA oxidation. Bonnefont et al. (1996) concluded that CPT II activity must be reduced below a critical threshold for LCFA oxidation in fibroblasts to be impaired. This critical threshold differs among tissues, thus providing a basis for the phenotypic heterogeneity of CPT II deficiency.
1999498
8651281
Martin et al. (1999) reported a patient with late-onset CPT II deficiency who had the Y628S mutation on 1 allele.
10398215
CPT2:c.1883A>C (p.Tyr628Ser)
NM_000098.2:c.1883A>C
NG_008035.1:g.22073A>C
NC_000001.10:g.53679173A>C
NP_000089.1:p.Tyr628Ser
missense
Y628S
TYR628SER
1p32.3
carnitine palmitoyltransferase 2
CPT2
Carnitine palmitoyltransferase II deficiency, infantile
CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY WITH HYPOKETOTIC HYPOGLYCEMIA
CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, HEPATOCARDIOMUSCULAR
CPT II DEFICIENCY, HEPATIC
CPT2 DEFICIENCY, INFANTILE
Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are: lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form that is usually mild and can manifest from infancy to adulthood. While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and is the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females.
<1 / 1 000 000
20301431
current
Pathogenic
germline
human
not provided
curation
In an infant with the infantile form of CPT II deficiency (600649) originally reported by Demaugre et al. (1991), Bonnefont et al. (1996) identified a homozygous 2399A-C transversion in the CPT2 gene, resulting in a tyr628-to-ser (Y628S) substitution. In vitro functional analysis in fibroblasts showed that the Y628S mutation resulted in 10% CPT II residual activity and markedly impaired oxidation of long-chain fatty acids, whereas the S113L (600650.0002) mutation found in the less severe adult form of the disorder (255110) resulted in 20% CPT II residual activity, without consequence on LCFA oxidation. Bonnefont et al. (1996) concluded that CPT II activity must be reduced below a critical threshold for LCFA oxidation in fibroblasts to be impaired. This critical threshold differs among tissues, thus providing a basis for the phenotypic heterogeneity of CPT II deficiency.
1999498
8651281
Martin et al. (1999) reported a patient with late-onset CPT II deficiency who had the Y628S mutation on 1 allele.
10398215
CPT2, TYR628SER
TYR628SER
CPT2
CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, INFANTILE