Screening for cerebrotendinos xantomatosis in adult patients with different neurological findings

Introduction and Objective: Cerebrotendinous xanthomatosis (CTX; OMIM#213700) is an autosomal recessive bile acid synthesis metabolism disorder characterized by accumulation of cholestanol in the body. The disease is characterized by the tendon xantomas, especially Achilles tendon, chronic diarrhea, juvenile cataract, ataxia, spastic paraparesis, epilepsy, parkinsonism, polyneuropathy, psychiatric disorders and signal changes in the dentate nucleus. The aim of this study is to selectively screen for CTX disease in the undiagnosed patients over 18 years of age, who are being followed up in the neurology clinic with different neurological findings. Materials and Methods: 220 undiagnosed patients hospitalized in the Neurology Service due to different neurological findings were evaluated with the Mignarri suspicion index. Plasma cholestanol level was sent to patients with Mignarri index above 100 and genetic analysis of CYP27A1 gene were performed for patients with Mignarri index above 200. Plasma cholestanol level was performed in 18 patients, genetic study was performed in 7 patients. Results: The mean age of 220 patients included in the study was 57.9 ± 18.7 years, 126 (%57.3) of them were women. Polyneuropathy was found in 163 (74.1%), ataxia in 55 (25.0%), epilepsy in 18 (8.2%), spastic paraparesis in 16 (7.3%), Parkinsonism in 12 (5.5%) and intellectual disability in 2 (0.9%) patients. In 36 cases (16.4%) psychiatric disorders were present. None of the 216 patients who underwent MRI examination no involvements were detected in the dentate nucleus. MRI examination of 30 patients was normal. Different involvements were detected in remained patients. In two patients had diarrhea that occured in childhood, in two patients had cataract that occured at an early age and one patient had Achilles tendon xanthoma. Plasma cholestanol levels and genetic tests of these patients were normal. The mean Mignarri suspicion index of the cases was found 53.9 ± 37.9 (minimum-maximum: 0-225). Mignarri index in 202 (91.8%) cases were below 100 score, in 15 (6.8%) cases were 100 -175 range and in 3 (1.4%) cases were 200 score and above. In one patient with signs of Parkinsonism c.1151C>T (p.P384L) pathogenic change was detected in one allele in the CYP27A1 gene and family screening recommended. Discussion and conclusion: CTX is progressive disease that presents with different neurological, psychiatric and systemic findings. In patients with different neurological findings, in case of family history and systemic findings, CTX should be considered and diagnostic tests should be requested. More studies are needed to increase the awareness of physicians on the subject in neurology practice, where routine patient density is very high. Key words: Cerebrotendinose xanthomatosis, CYP27A1 gene, cataract, Achilles tendon xanthoma, neurological findings, Mignarri index.