Rapid, Cost-Effective Gene Mutation Screening for Carnitine Palmitoyltransferase II Deficiency Using Whole Blood on Filter Paper‪.‬

Rapid, Cost-effective Gene Mutation Screening for Carnitine Palmitoyltransferase 11 Deficiency Using Whole Blood on Filter Paper, David Smail, Leah Gambino, Christopher Boles, and Georgirene D. Vladutiu* (State University of New York at Buffalo, 936 Delaware Ave., Buffalo, NY 14209; * author for correspondence: fax 716-878-7980, email gdv@acsu.buffalo.edu) Carnitine palmitoyltransferase II (CPT II; EC 2.3.1.21), an enzyme associated with the inner mitochondrial membrane, is important in the transport of long-chain fatty acids from the cytosol into the mitochondrial matrix for [beta]-oxidation (1). CPT II deficiency presents as three distinct clinical phenotypes: adult myopathic (MIM 255110), lethal neonatal (MIM 600649), and a severe infantile phenotype (2). The adult form is the most common lipid myopathy in humans and is characterized by muscle pain, stiffness, and myoglobinuria triggered by exercise, fasting, anesthesia, or other metabolic stressors (3). CPT II is a homotetramer (4) encoded by a gene (MIM 600650) on chromosome 1p32 (5) that spans 20 kb and contains five exons ranging in length from 81 to 1305 by (6). At least 15 mutations in CPT2 are associated with the adult and infantile disorders (7-9). CPT II deficiency is an autosomal recessive disorder (3, 9); however, recent biochemical and molecular evidence suggests the existence of manifesting carriers, predicting that the prevalence of the disease may be even higher than previously believed (9).