Patients with Lately Diagnosed Cerebrotendinous Xanthomatosis

Neurodegener Dis 2019;19(5-6):218-224. doi: 10.1159/000506770.

PMID: 32349000

Gulshan Yunisova , Zeynep Tufekcioglu , Okan Dogu

Highligts: Although the symptoms begin commonly in infancy, CTX diagnosis is often delayed. In CTX disease, early diagnosis and treatment is crucial in preventing clinical deterioration.

Abstract

Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive inborn lipid storage disease caused by various pathogenic mutations in the CYP27A1 gene. Despite the fact that the symptoms generally begin in infancy, CTX diagnosis is frequently delayed. In this study, we describe seven Turkish CTX patients who were diagnosed late despite early clinical signs and came from six different families.

Methods: Clinical, laboratory, imaging, and genetic findings of CTX patients were collected from two centers specialized in movement disorders and retrospectively evaluated: the Department of Neurology, Faculty of Medicine, Istanbul University, and the Department of Neurology, Faculty of Medicine, Mersin University.

Results: Despite a mean onset age of 12.4 ± 10.6 years, all patients were diagnosed with CTX after neurological symptoms developed. Their mean age at diagnosis was 38.7 ± 9.6 years. The mean follow-up period was 28 months (range: 3-60 months). Unexplained chronic diarrhea (42%), febrile convulsion (42%), juvenile cataract (85%), childhood depression and autism (14%), parkinsonism (14%), and intellectual impairment (100%) were the most frequent initial clinical abnormalities in our cohort. The pyramidal-cerebellar syndrome (85%) and extrapyramidal signs were the most common neurological findings (42%). All patients were genetically confirmed. Serum cholestanol levels were elevated in all patients, but levels were reduced in six of them after therapy with chenodeoxycholic acid (CDCA).

Conclusion: This cohort represents Turkey's biggest CTX case series. As a result of CDCA treatment, all patients demonstrated improvement in gastrointestinal symptoms and stability of neurological symptoms, i.e., no further development of neurological abnormalities was seen throughout this treatment. As a result, early detection and treatment are critical for avoiding clinical deterioration.

Keywords: CYP27A1 gene, Cerebrotendinous xanthomatosis, Chenodeoxycholic acid, Juvenile cataract, Lipid storage disorder, Xanthoma.