Cerebrotendinous xanthomatosis: a treatable hereditary cholesterol metabolism disorder


Yılmaz M., Türkyılmaz A., Adanur Sağlam K., Çebi N., Çebi A. H.

57th European Society of Human Genetics (ESHG) Conference, Berlin, Almanya, 1 - 04 Haziran 2024, ss.1027

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Berlin
  • Basıldığı Ülke: Almanya
  • Sayfa Sayıları: ss.1027
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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