title: Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.
abstract: Myelination is a complex, developmentally regulated process whereby myelin proteins and lipids are coordinately expressed by myelinating glial cells. Homozygosity mapping in nine patients with childhood onset spasticity, dystonia, cognitive dysfunction, and periventricular white matter disease revealed inactivating mutations in the FA2H gene. FA2H encodes the enzyme fatty acid 2-hydroxylase that catalyzes the 2-hydroxylation of myelin galactolipids, galactosylceramide, and its sulfated form, sulfatide. To our knowledge, this is the first identified deficiency of a lipid component of myelin and the clinical phenotype underscores the importance of the 2-hydroxylation of galactolipids for myelin maturation. In patients with autosomal-recessive unclassified leukodystrophy or complex spastic paraparesis, sequence analysis of the FA2H gene is warranted.
authors.affiliation: Metabolic Disease Unit, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hama
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: John Moshe
authors.initials: JM
authors.lastname: Gomori
authors.forename: Itai
authors.initials: I
authors.lastname: Berger
authors.forename: Dov
authors.initials: D
authors.lastname: Soffer
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Korman
authors.forename: Ilana
authors.initials: I
authors.lastname: Taustein
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003241:Consanguinity; D004421:Dystonia / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D020336:Paraparesis, Spastic / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D006899:Mixed Function Oxygenases; C019081:fatty acid alpha-hydroxylase