title: SLC22A5 mutations in a patient with systemic primary carnitine deficiency: the first Korean case confirmed by biochemical and molecular investigation.
abstract: Systemic primary carnitine deficiency (CDSP) is a rare autosomal recessive disorder that presents episodic periods of hypoketotic hypoglycemia. The main symptoms of CDSP are skeletal and cardiac myopathy. CDSP is caused by a defect in plasma membrane uptake of carnitine, ultimately caused by the SLC22A5 gene. We report the case of a Korean patient with CDSP. He had an abnormal free carnitine level of 5.56 μmol/L (reference range, RR 10.4~87.1 μmol/L) and a palmitoylcarnitine level of 0.27 μmol/L (RR 0.5~9.7 μmol/L) in a newborn screening test. The patient showed an ammonia level of 129.4 ug/dL (RR, 25~65 ug/dL), a lactate level of 4.5 mmol/L (RR, 0.5-2.2 mmol/L), and a free carnitine level of 10.3 μmol/L (RR, 36-74 μmol/L) in blood. After PCR-sequencing analysis of the SLC22A5 gene, the patient was found to be a compound heterozygote for c.506G>A (p.R169Q) and c.1400C>G (p.S467C) mutations. These missense mutations are reported previously. The patient was started on L-carnitine supplement after CDSP diagnosis. The patient was treated with L-carnitine to reach a normal free carnitine level and has remained asymptomatic up to the current age of 21 months. The plasma free carnitine level normalized to 66.6 μmol/L at 4 weeks after treatment. To the best of our knowledge, this is the first report of a CDSP patient confirmed by molecular genetic investigation.
authors.affiliation: Department of Laboratory Medicine and Genetics; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Ahn
authors.initials: YA
authors.lastname: Yoon
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Yong-Wha
authors.initials: YW
authors.lastname: Lee
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
mesh_terms: D000641:Ammonia / Q000097:blood; D001483:Base Sequence; D009202:Cardiomyopathies / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D002331:Carnitine / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007231:Infant, Newborn; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D000074058:Solute Carrier Family 22 Member 5; D016896:Treatment Outcome
chemical_list: D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D019344:Lactic Acid; D000641:Ammonia; D002331:Carnitine