title: Non-manifesting Refsum heterozygotes carrying the c.135-2A>G PAHX gene transition.
abstract: So far, subjects heterozygous for PAHX mutations are regarded as non-symptomatic. In the 24-year-old, HIV-negative daughter and the 26-year-old, HIV-negative son of a patient with Refsum disease due to the homozygous c.135-2A>G transition at the splice site before exon 3 of the PAHX gene, slight abnormalities suggestive of the disease became apparent. The daughter reported a single fever cramp in childhood, recurrent, short-lived amaurotic episodes after getting up from supine, short-sightedness, hypoacusis, and restless legs. The son complained about restless legs, hyperhidrosis, hypoacusis, and bulbar oscillations. Though both children carried the same mutation as their mother in the heterozygous form, clinical neurologic examination, nerve conduction studies and serum phytanic acid concentration were normal in both of them, implying that the described abnormalities were not causally related to the PAHX mutation. In the absence of elevated phytanic acid concentrations, clinical neurologic abnormalities in heterozygous relatives of Refsum patients are not attributable to heterozygosity for PAHX mutations.
authors.affiliation: Krankenanstalt Rudolfstiftung, Vienna, Austria. fifigs1@yahoo.de
authors.forename: Josef
authors.initials: J
authors.lastname: Finsterer
authors.forename: Günther
authors.initials: G
authors.lastname: Regelsberger
authors.forename: Till
authors.initials: T
authors.lastname: Voigtländer
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001766:Blindness / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics; D010831:Phytanic Acid / Q000097:blood; D012035:Refsum Disease / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D012148:Restless Legs Syndrome / Q000235:genetics
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D010831:Phytanic Acid; D006899:Mixed Function Oxygenases; C102623:PHYH protein, human