title: Carnitine membrane transporter deficiency: a long-term follow up and OCTN2 mutation in the first documented case of primary carnitine deficiency.
abstract: Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a generation ago and have together been treated for more than 50 patient years. Treatment improved tissue carnitine stores (proven in two) and eliminated most of the signs and symptoms of carnitine deficiency. All three have continued to respond to carnitine therapy and remain well except for the irreversible sequelae of the pretreatment illnesses. We demonstrate here that transformed lymphocytes from the first documented case of plasma membrane carnitine transporter deficiency fail to take up carnitine from the medium. The analysis of the cDNA of this patient and his parents revealed a homozygous frameshift mutation, 1027delT in exon 4. The resulting polypeptide terminates after amino acid 295. His parents are heterozygous for this mutation. The deletion resulted in predominately abnormal mRNA splicing with either a 13 or 19bp insertion between the junction of exons 3 and 4. The 13/19bp insertions were found in both parents, predominantly in cis with the deletion, and rarely seen with normal alleles from either parents or controls.
authors.affiliation: Department of Psychiatry, UCLA, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA. scederbaum@mednet.ucla.edu
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cederbaum
authors.forename: Samantha
authors.initials: S
authors.lastname: Koo-McCoy
authors.forename: Ingrid
authors.initials: I
authors.lastname: Tein
authors.forename: Betty Y L
authors.initials: BY
authors.lastname: Hsu
authors.forename: Arupa
authors.initials: A
authors.lastname: Ganguly
authors.forename: Eric
authors.initials: E
authors.lastname: Vilain
authors.forename: Katrina
authors.initials: K
authors.lastname: Dipple
authors.forename: Ljerka
authors.initials: L
authors.lastname: Cvitanovic-Sojat
authors.forename: Charles
authors.initials: C
authors.lastname: Stanley
mesh_terms: D000293:Adolescent; D000328:Adult; D002331:Carnitine / Q000172:deficiency*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; 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; D002331:Carnitine