title: Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency.
abstract: Systemic carnitine deficiency (CDSP) (McKusick 212140) is a rare autosomal recessive disease caused by defective plasma membrane uptake of carnitine. The disease is characterized by Reye syndrome, progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonaemia. CDSP is a treatable disease provided an early diagnosis is made and prompt treatment with L-carnitine is initiated. The biochemical diagnosis of the disease is based on the findings of very low plasma and tissue carnitine concentrations. Recently, a human gene, SLC22A5, encoding a sodium-dependent high-affinity carnitine transporter OCTN2 was cloned from human kidney and shown to be mutated in systemic carnitine deficiency. Here we report two unrelated Saudi CDSP patients who were detected by tandem mass spectrometric analysis (MS/MS) of blood spots. Studies in skin fibroblasts from the two patients showed a severely reduced carnitine uptake. Subsequent molecular studies led to the identification of two novel missense mutations in the OCTN2 gene in the two patients.
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Z
authors.initials: Z
authors.lastname: Rahbeeni
authors.forename: F M
authors.initials: FM
authors.lastname: Vaz
authors.forename: K
authors.initials: K
authors.lastname: Al-Hussein
authors.forename: M P
authors.initials: MP
authors.lastname: Bucknall
authors.forename: J
authors.initials: J
authors.lastname: Ruiter
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: M S
authors.initials: MS
authors.lastname: Rashed
mesh_terms: D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D027701:Organic Cation Transport Proteins; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; C116917:acylcarnitine; D002331:Carnitine