Mutations in the sterol 27‐hydoxylase gene (<i>CYP27A</i>) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis

Journal of Inherited Metabolic Disease - Tập 25 Số 6 - Trang 501-513 - 2002
Peter T. Clayton1,2, Aad Verrips3, Erik A. Sistermans4, Anúska Mann2, Giorgina Mieli–Vergani5, Ron A. Wevers6
1Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
2Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, and Great Ormond Street Hospital for Children NHS Trust, London, UK
3Department of Paediatric Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands
4Department of Human Genetics, University Medical Centre St Radboud, Nijmegen, The Netherlands
5Department of Child Health, King’s College Hospital, London, UK
6Department of Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands.

Tóm tắt

AbstractFollow‐up investigations were undertaken on a previously reported patient who had severe familial giant cell hepatitis in infancy associated with substantially increased urinary excretion of bile alcohol glucuronides. By the age of 11 years, he had developed a profile of cholanoids in plasma and urine that closely resembled the pattern seen in cerebrotendinous xanthomatosis (CTX). Sequencing of the sterol 27‐hydroxylase gene (CYP27A) showed that he was homozygous for a deletion (525/526delG) that causes a frameshift and a premature stop codon. This genotype has previously been described in an adult female with classical symptoms of CTX (tendon xanthomata, cataracts and deteriorating cognitive function). A review of past medical histories of a group of patients with CTX revealed that prolonged neonatal cholestatic jaundice was common. The family histories also revealed fetal and neonatal deaths among siblings of patients with CTX. We conclude that defective activity of cholesterol 27‐hydroxylase can lead to neonatal cholestatic jaundice (‘hepatitis of infancy’), which may be self‐limiting. After a latent period, however, progressive accumulation of cholesterol and cholestanol can lead to the xanthomata, neurodegeneration, cataracts and atherosclerosis that are typical of CTX.

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Journal of Inherited Metabolic Disease

Tập 25 Số 6

501-513

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