Autopsy case of the neonatal form of carnitine palmitoyltransferase-II deficiency triggered by a novel disease-causing mutation del1737C.
Carnitine palmitoyltransferase-II (CPT-II) deficiency is an autosomal recessive disease involving mitochondrial long-chain fatty acid oxidation that results in a distinct clinical phenotype. Reported herein is an autopsy case of the neonatal form of CPT-II deficiency in a 2-day-old Japanese boy who died due to a severe hepatocardiomuscular disease with an extremely early onset. Autopsy examination indicated massive pulmonary atelectasis with intra-alveolar hemorrhage, and the patient had marked cardiomegaly and hepatomegaly, both of which demonstrated the presence of abundant intracytoplasmic steatosis. Three years after the autopsy examination, CPT-II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper from the patient's younger sister at the age of 1. The younger sister also died due to sudden onset of cardiopulmonary arrest; a remarkable increase of long-chain (C16-18) acylcarnitines was detected on tandem mass spectrometry (TMS). Decreased CPT-II expression was detected in the liver, heart and kidney of the patient. Furthermore, del1737C, a novel mutation of the CPT-II gene, was detected as well as a known GA transition at codon 174. Eventually, laboratory and autopsy findings led to diagnosis of the neonatal form of CPT-II deficiency. TMS can be expected to be widely used to detect metabolic disorders in neonates.
Semba
Shuho
S
Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. semba@med.kobe-u.ac.jp
Yasujima
Hidehiro
H
Takano
Tomoko
T
Yokozaki
Hiroshi
H
D001344:Autopsy; D006332:Cardiomegaly / Q000151:congenital; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006529:Hepatomegaly / Q000151:congenital; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D010375:Pedigree; D001261:Pulmonary Atelectasis / Q000209:etiology; D053719:Tandem Mass Spectrometry
D002334:Carnitine O-Palmitoyltransferase