Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies.

Abstract

Reported cases of carnitine palmitoyltransferase II (CPT II) deficiency are characterized only by a muscular symptomatology in young adults although the defect is expressed in extramuscular tissues as well as in skeletal muscle. We describe here a CPT II deficiency associating hypoketotic hypoglycemia, high plasma creatine kinase level, heart beat disorders, and sudden death in a 3-mo-old boy. CPT II defect (-90%) diagnosed in fibroblasts is qualitatively similar to that (-75%) of two "classical" CPT II-deficient patients previously studied: It resulted from a decreased amount of CPT II probably arising from its reduced biosynthesis. Consequences of CPT II deficiency studied in fibroblasts differed in both sets of patients. An impaired oxidation of long-chain fatty acids was found in the proband but not in patients with the "classical" form of the deficiency. The metabolic and clinical consequences of CPT II deficiency might depend, in part, on the magnitude of residual CPT II activity. With 25% residual activity CPT II would become rate limiting in skeletal muscle but not in liver, heart, and fibroblasts. As observed in the patient described herein, CPT II activity ought to be more reduced to induce an impaired oxidation of long-chain fatty acids in these tissues. (J. Clin. Invest.

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

“…The infantile form of CPT II deficiency usually manifests between 6 months and 2 years of age with hypoketotic hypoglycemia, hepatomegaly, and raised plasma creatine kinase levels (Bonnefont et al, 1999;Demaugre et al, 1991). Cardiac manifestations include dilated hypertrophic cardiomyopathy and arrhythmias (Demaugre et al, 1991;Taroni et al, 1992;VianeySaban et al, 1995).…”

“…Cardiac manifestations include dilated hypertrophic cardiomyopathy and arrhythmias (Demaugre et al, 1991;Taroni et al, 1992;VianeySaban et al, 1995). Other clinical and laboratory features may include episodic weakness, encephalopathy, seizures, respiratory distress, metabolic acidosis, increased serum aminotransferase and ammonia, and decreased serum carnitine (Elpeleg et al, 1993;Ross et al, 1996;Taroni et al, 1992).…”

“…Other clinical and laboratory features may include episodic weakness, encephalopathy, seizures, respiratory distress, metabolic acidosis, increased serum aminotransferase and ammonia, and decreased serum carnitine (Elpeleg et al, 1993;Ross et al, 1996;Taroni et al, 1992). In this group of patients, CPT II activity in fibroblasts ranges from 4% to 10% of the activity in control fibroblasts (Demaugre et al, 1991;Elpeleg et al, 1993). [9, H]Myristate oxidation in fibroblasts is usually less than 10% of the control values (Bonnefont et al, 1996).…”

Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy

“…Carnitine palmitoyltransferase II deficiency is one of the most common inherited metabolic disorders and is categorized into three forms: neonatal (OMIM 608836) [5], infantile (OMIM 600649) [5], and adult (OMIM 255110) [6]. The infantile form usually manifests at 6-24 months of age as recurrent attacks of hypoketotic hypoglycemia, resulting in coma and seizures, liver failure, and transient hepatomegaly.…”

A novel splice site mutation in neonatal carnitine palmitoyl transferase II deficiency

“…The lethal neonatal form presents with hypoketotic hypoglycemia and severe hepatomuscular symptoms (Demaugre et al 1991). The infantile form shows recurrent attacks of acute liver failure with hypoketotic hypoglycemia, resulting in coma and seizures, and transient hepatomegaly.…”