Fatal Carnitine Palmitoyltransferase II Deficiency in a Newborn: New Phenotpic Features

Abstract

We describe the term male infant of asymptomatic, healthy nonconsanguineous parents presenting on the first day of life with nonketotic hypoglycemia, seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and ventricular arrhythmias. Cranial ultrasound revealed cystic dysplasia with several foci of hyperechogenicity within the right basal ganglia. Free carnitine was markedly decreased in the urine and plasma with a pronounced elevation of plasma long-chain acylcarnitines. Fibroblast carnitine palmitoyltransferase II activity was reduced to 26% and 38% in the father and mother, respectively. The infant expired on day 5 of life from malignant ventricular tachy-arrhythmias. Diffuse lipid accumulation was evident at autopsy, including in the liver, heart, kidney, adrenal cortex, skeletal muscle, and lungs. This new case of infantile CPT-II deficiency illustrates the severity of the early onset form of CPT-II deficiency.

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

“…This presentation is fatal, leading to death in the neonatal period as was observed in our case (Albers et al, 2001a;Elpeleg et al, 2001;Gellera et al, 1992;Hug et al, 1991;Land et al, 1995;North et al, 1995;Pierce et al, 1999;Sharma et al, 2003;Smeets et al, 2003;Taroni et al, 1994;Vladutiu et al, 2002b;Witt et al, 1991;Zinn et al, 1991). Pregnancy may be complicated by oligohydramnios, and prenatal screening may show malformations including large ventricles, agenesis of the corpus callosum, intraventricular calcifications, and cystic dysplasia of the brain and the kidneys (Elpeleg et al, 2001;North et al, 1995).…”

“…In addition to dysmorphia, the clinical features include Carnitine palmitoyltransferase II studies (units: nmol palmitoyl coenzyme A formed/min/mg protein). North et al, 1995;Pierce et al, 1999). Central nervous system anomalies include ventriculomegaly, periventricular cysts, subarachnoid and subependymal hemorrhages, calcifications, and polymicrogyria, which is thought to result from abnormal neuronal migration.…”

“…The infantile form, which usually presents in early childhood with fasting-induced hypoketotic hypoglycemia, liver failure, cardiomyopathy, and peripheral neuropathy, is potentially fatal, although treatable if diagnosed early (Hug et al, 1991;Taroni et al, 1992). The perinatal form is the least common clinical presentation of CPT II deficiency and is almost universally and rapidly fatal (Elpeleg et al, 2001;Gellera et al, 1992;North et al, 1995;Pierce et al, 1999;Taroni et al, 1994;Vladutiu et al, 2002b). The phenotypic variability of CPT II deficiency is fascinating.…”

Cerebral Lipid Accumulation Detected by MRS in a Child with Carnitine Palmitoyltransferase 2 Deficiency: A Case Report and Review of the Literature on Genetic Etiologies of Lipid Peaks on MRS

“…In addition, even though the authors are not aware of a case report of Refsum disease causing an abnormal lipid peak on MRS, it is likely that some patients with this condition will exhibit lipid peaks, as fat deposits are found in the globus pallidus during autopsy (Allen et al 1978). Lipid droplets and elevated long-chain acylcarnitine concentrations have been found in various tissues in patients with neonatal-onset CPT2 deficiency, including liver, kidney, skeletal muscle, heart, lung, and adrenal (North et al 1995;Pierce et al 1999). It is likely that our patient had cerebral accumulation of long-chain acylcarnitines, giving rise to the lipid peak detected on MRS.…”

“…Severe forms of CPT2 deficiency can present with encephalopathy, intractable seizures with multifocal spike discharges, hemorrhages, periventricular cysts, ventriculo- megaly, partial absence of the corpus callosum, Dandy--Walker malformation with severe hydrocephalus, polymicrogyria, gray matter and neuroglial heterotopias, and periventricular white matter calcifications (North et al 1995;Pierce et al 1999;Elpeleg et al 2001;Isackson et al 2008;Meir et al 2009). To our knowledge, brain MRS has never before been reported in a patient with CPT2 deficiency.…”