Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.

Francois Maillot, Kimberly A Chapman, Henk J Blom, Sufin Yap, Allyson Terry, Isabel Tavares de Almeida, Markéta Pavlíková, Siobhan O'Sullivan, Helene Ogier, Tara M Morrison, Jenny McNulty, Philip D Mayne, Andrew A M Morris, Miriam C H Janssen, Martina Huemer, Michel Hochuli, Mick J Henderson, Ellen Crushell, Anupam B Chakrapani, Tawfeg I M Ben-Omran, Generoso Andria, Saikat Santra, Viktor Kožich

Journal: Journal of inherited metabolic disease 2017;40(1):49-74

PMID: 27778219

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Abstract

Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 μmol/L. Nevertheless, we recommend keeping the concentration below 100 μmol/L because levels fluctuate and the complications associated with high levels are so serious.

Address: Institute of Human Development, University of Manchester, Manchester, UK. [email protected].; Willink Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK. [email protected].; Institute of Inherited Metabolic Disorders, Charles University in Prague-First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.; Clinical IMD, Birmingham Children's Hospital, Birmingham, UK.; Department of translational medicine, Federico II University, Naples, Italy.; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.; Department of Metabolic Medicine, Great Ormond Street Hospital, London, UK.; National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.; Willink Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK.; Biochemical Genetics, St James' University Hospital, Leeds, UK.; Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zürich, Zurich, Switzerland.; Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Zurich, Switzerland.; Rare Disease Initiative Zürich, University of Zürich, Zurich, Switzerland.; Dept. of Paediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria.; Department of Internal medicine, Radboud University Medical Center, Nijmegen, Netherlands.; CHRU de Tours, Université François Rabelais, Tours, France.; Newborn Bloodspot Screening Laboratory, Temple Street Children's University Hospital, Dublin, Ireland.; HCU Network, Baulkham Hills, Australia.; Service de Neurologie Pédiatrique et des Maladies Métaboliques, Hôpital Robert Debré, Paris, France.; Royal Belfast Hospital for Sick Children, Belfast, UK.; Metabolism & Genetics Group, Faculty of Pharmacy at University of Lisboa, Lisboa, Portugal.; Institute of Human Development, University of Manchester, Manchester, UK.; Dietetic Department, Alder Hey Hospital, Liverpool, UK.; Dept of Inherited Metabolic Diseases, Sheffield Children's Hospital, Sheffield, UK.; Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, University Medical Centre Freiburg, Freiburg im Breisgau, Germany.; Division of Genetic and Metabolism, Children's National Health System, Washington, DC, USA.

DOI: 10.1007/s10545-016-9979-0

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MeSH Terms: Betaine, Cystathionine beta-Synthase, Homocysteine, Homocystinuria, Humans, Methionine, Pyridoxine