Akanuma J, Wataya K, Matubara Y, Yamamoto T, Kira J, Narisawa K
Department of Neurology, Fukushima Medical College Hikarigaoka, Japan.
Rinsho Shinkeigaku. 1997 Jun;37(6):532-5.
Carnitine palmitoyltransferase (CPT), one of the key enzymes of beta-oxidation, translocates long-chain fatty acids from the cytosolic compartment into the mitochondrial matrix to undergo beta-oxidation. Recently, the CPT system has been characterized to consist of two distinct mitochondrial membrane-bound enzymes, CPT I, located on the inner side of the outer mitochondrial membrane, and CPT II, located on the inner mitochondrial membrane. We have investigated a Japanese patient with muscular manifestations who was previously reported as CPT deficiency. Enzymatic analysis of her cultured lymphoblasts revealed that CPT II activity was reduced to 5.8%, indicating that the patient suffered from CPT II deficiency. Molecular analysis identified a missense mutation, a glutamate (174)-to-lysine substitution (E174K), in the CPT II cDNA. The patient was homozygous for the mutation. The presence of the mutation was confirmed by PCR-RFLP with a mismatched primer to generate Mbo II recognition sequence at the mutation site. It has been reported that CPT II deficiency manifests as two different clinical phenotypes: a muscular form and a hepatocardiomuscular form. To our knowledge, this is the first case of CPT II deficiency with muscular symptoms to be characterized by molecular analysis in Japan.
肉碱棕榈酰转移酶(CPT)是β-氧化的关键酶之一,它将长链脂肪酸从胞质区室转运到线粒体基质中进行β-氧化。最近,CPT系统已被鉴定为由两种不同的线粒体膜结合酶组成,即位于线粒体外膜内侧的CPT I和位于线粒体内膜的CPT II。我们研究了一名有肌肉表现的日本患者,该患者先前被报道为CPT缺乏症。对其培养的淋巴母细胞进行酶分析发现,CPT II活性降至5.8%,表明该患者患有CPT II缺乏症。分子分析在CPT II cDNA中鉴定出一个错义突变,即谷氨酸(174)被赖氨酸替代(E174K)。该患者为该突变的纯合子。通过使用错配引物进行PCR-RFLP在突变位点产生Mbo II识别序列,证实了突变的存在。据报道,CPT II缺乏症表现为两种不同的临床表型:肌肉型和肝心肌型。据我们所知,这是日本首例通过分子分析鉴定出的有肌肉症状的CPT II缺乏症病例。