Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized.
BACKGROUND
Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurodegenerative disorder caused by 27-sterol hydroxylase (CYP27) deficiency.


OBJECTIVE
To describe clinical features and results of genetic analysis in a family with CTX.


METHODS
Case report.


METHODS
University hospital. Subjects A 54-year-old woman with CTX, her family members, and 115 white control subjects.


METHODS
Results of clinical evaluation and magnetic resonance imaging of the brain in the affected subject; results of mutation analysis of the CYP27 coding sequence in the patient, her parents, and the control subjects.


RESULTS
The proband and her affected sibling had classic features of CTX, including presenile cataracts, tendon xanthomas, diarrhea, and a complex neurodegenerative disorder. They were somewhat atypical, however, because their cataracts were congenital, cognitive impairment had been noted in childhood, and the white matter involvement was more severe than usual. The proband was shown to be homozygous for CYP27 mutation R362C. Similar analysis of 115 control subjects identified 1 subject who was a heterozygous carrier for this same CYP27 mutation.


CONCLUSIONS
The prevalence of CTX due to CYP27 mutation R362C alone is approximately 1 per 50,000 among white individuals. Although the disorder is rare, this incidence is substantially greater than previously recognized. Greater awareness of CTX is important because specific treatment is available.
Lorincz
Matthew T
MT
Department of Neurology, University of Michigan, Ann Arbor, 48109, USA.
Rainier
Shirley
S
Thomas
Donald
D
Fink
John K
JK
D001120:Arginine / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D053493:Cholestanetriol 26-Monooxygenase; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D013250:Steroid Hydroxylases / Q000172:deficiency / Q000235:genetics*; D019294:Xanthomatosis, Cerebrotendinous / Q000453:epidemiology* / Q000235:genetics*
D002635:Chenodeoxycholic Acid; D001120:Arginine; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D003545:Cysteine