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It is a rare form of CPT II deficiency that has been reported in less than 20 families.

Affected infants experience hypoketotic hypoglycemia, liver and respiratory failure and can present with cardiomyopathy, muscle hypotonia, liver calcification, cystic dysplastic kidneys and malformations of the brain due to a neuronal migration defect. Seizures and coma can occur as well as cardiac arrhythmias that generally lead to cardiac arrest in the perinatal/ early infantile period. Death occurs within days to months.

The severe neonatal CPT II deficiency is caused by homozygous or compound heterozygous CPT2 mutations that typically result in complete loss of activity of the CPT II enzyme.

The diagnosis is made by an initial tandem mass spectrometry of serum/plasma acylcarnitines followed by mutation analysis and measurements of CPTII enzyme activity in fresh circulating lymphocytes, muscle or skin fibroblasts.

The differential diagnosis should include severe forms of carnitine-acylcarnitine translocase deficiency (CACT) and very-long-chain acyl-CoA dehydrogenase deficiency (see these terms).

Prenatal diagnosis is available based on a combination of enzymatic and molecular testing (if mutations have been identified in the proband).

Transmission is autosomal recessive.

Treatment is only symptomatic.

Prognosis is poor. The neonatal form is almost always lethal during the first months of life.