Research Information System
57th European Society of Human Genetics (ESHG) Conference, Berlin, Germany, 1 - 04 June 2024, pp.1027
Background/Objectives: Cerebrotendinous xanthomatosis (CTX)
is a rare autosomal ressesive disorder of cholesterol metabolism
and characterized by abnormal deposition of cholestanol in
tissues such as brain, spinal cord, eye and tendons. In this study,
we aimed report clinical and genetic characteristics of 5 CTX
patients.
Methods: All patients were evaluated with family history,
neurological examination, brain magnetic resonance imaging
(MRI) and electromyography. All cases were investigated with
the hereditary ataxia gene panel using the next generation
sequencing method.
Results: The median age of the patients at symptom onset was
21 years, and the median age at diagnosis was 35 years. In 4 out of
5 families, the parents were consanguineous. In terms of clinical
findings, cataract was present in 3 (60%), polyneuropathy in 2
(40%), developmental delay/intellectual disability in all (100%),
seizure in 2 (40%), osteoporosis in 1 (20%), and ataxia in 4 (80%). In
brain MRI analysis, cerebral and cerebellar atrophy, hyperintensity
in dentate nucleus were reported. Three different homozygous
variants were detected in CYP27A1 gene (NM_000784.4:
c.1476+2T > C, c.1_5delATGGC (p.Met1fs*178), c.646G>C
(p.Ala216Pro) in these patients. The frameshift (c.1_5delATGGC,
p.M1fs*178) variant revealed in 2 different cases was the novel
variant. Colestanol levels of two patients are 38.1 ug/ml and
41.79 ug/ml.
Conclusions: Timely detection and treatment are key to
prevent severe morbidity and mortality in CTX patients. Early
initiation of oral chenodeoxy-colic-acid therapy is the treatment
choice for neurological and non-neurological symptoms. The
addition of the CYP27A1 gene to the hereditary ataxia, spastic
paraplegia and cataract gene panels will contribute to the early
diagnosis of CTX patients.
Conflict of Interest: None declared