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Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report.
Koyama, Shingo; Okabe, Yuma; Suzuki, Yuya; Igari, Ryosuke; Sato, Hiroyasu; Iseki, Chifumi; Tanji, Kazuyo; Suzuki, Kyoko; Ohta, Yasuyuki.
Afiliación
  • Koyama S; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan. skoyama@med.id.yamagata-u.ac.jp.
  • Okabe Y; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Suzuki Y; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Igari R; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Sato H; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Iseki C; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Tanji K; Department of Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
  • Suzuki K; Department of Psychiatry, Koishikawa Tokyo Hospital, 4-45-16 Otsuka, Bunkyo-ku, Tokyo, 112-0012, Japan.
  • Ohta Y; Department of Internal Medicine III, Division of Neurology and Clinical Neuroscience, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
BMC Neurol ; 22(1): 193, 2022 May 25.
Article en En | MEDLINE | ID: mdl-35614401
BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy. CASE PRESENTATION: The proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20). CONCLUSIONS: Our cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Catarata / Xantomatosis / Xantomatosis Cerebrotendinosa Tipo de estudio: Prognostic_studies / Screening_studies Límite: Humans / Male País/Región como asunto: Asia Idioma: En Revista: BMC Neurol Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Catarata / Xantomatosis / Xantomatosis Cerebrotendinosa Tipo de estudio: Prognostic_studies / Screening_studies Límite: Humans / Male País/Región como asunto: Asia Idioma: En Revista: BMC Neurol Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón