title: Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.
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.
authors: Institute of Human Development, University of Manchester, Manchester, UK. Andrew.morris@cmft.nhs.uk.|Willink Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK. Andrew.morris@cmft.nhs.uk.
authors: Andrew A M
authors: AA
authors: Morris
authors: Institute of Inherited Metabolic Disorders, Charles University in Prague-First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
authors: Viktor
authors: V
authors: Kožich
authors: Clinical IMD, Birmingham Children's Hospital, Birmingham, UK.
authors: Saikat
authors: S
authors: Santra
authors: Department of translational medicine, Federico II University, Naples, Italy.
authors: Generoso
authors: G
authors: Andria
authors: Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
authors: Tawfeg I M
authors: TI
authors: Ben-Omran
authors: Department of Metabolic Medicine, Great Ormond Street Hospital, London, UK.
authors: Anupam B
authors: AB
authors: Chakrapani
authors: National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.
authors: Ellen
authors: E
authors: Crushell
authors: 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.
authors: Mick J
authors: MJ
authors: Henderson
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zürich, Zurich, Switzerland.
authors: Michel
authors: M
authors: Hochuli
authors: 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.
authors: Martina
authors: M
authors: Huemer
authors: Department of Internal medicine, Radboud University Medical Center, Nijmegen, Netherlands.
authors: Miriam C H
authors: MC
authors: Janssen
authors: CHRU de Tours, Université François Rabelais, Tours, France.
authors: Francois
authors: F
authors: Maillot
authors: Newborn Bloodspot Screening Laboratory, Temple Street Children's University Hospital, Dublin, Ireland.
authors: Philip D
authors: PD
authors: Mayne
authors: National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.
authors: Jenny
authors: J
authors: McNulty
authors: HCU Network, Baulkham Hills, Australia.
authors: Tara M
authors: TM
authors: Morrison
authors: Service de Neurologie Pédiatrique et des Maladies Métaboliques, Hôpital Robert Debré, Paris, France.
authors: Helene
authors: H
authors: Ogier
authors: Royal Belfast Hospital for Sick Children, Belfast, UK.
authors: Siobhan
authors: S
authors: O'Sullivan
authors: Institute of Inherited Metabolic Disorders, Charles University in Prague-First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
authors: Markéta
authors: M
authors: Pavlíková
authors: Metabolism & Genetics Group, Faculty of Pharmacy at University of Lisboa, Lisboa, Portugal.
authors: Isabel Tavares
authors: IT
authors: de Almeida
authors: Institute of Human Development, University of Manchester, Manchester, UK.|Dietetic Department, Alder Hey Hospital, Liverpool, UK.
authors: Allyson
authors: A
authors: Terry
authors: Dept of Inherited Metabolic Diseases, Sheffield Children's Hospital, Sheffield, UK.
authors: Sufin
authors: S
authors: Yap
authors: Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, University Medical Centre Freiburg, Freiburg im Breisgau, Germany.
authors: Henk J
authors: HJ
authors: Blom
authors: Division of Genetic and Metabolism, Children's National Health System, Washington, DC, USA.
authors: Kimberly A
authors: KA
authors: Chapman
mesh_terms: D001622:Betaine / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D006710:Homocysteine / Q000378:metabolism; D006712:Homocystinuria / Q000178:diet therapy* / Q000188:drug therapy*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D011736:Pyridoxine / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D001622:Betaine; D008715:Methionine; D003541:Cystathionine beta-Synthase; D011736:Pyridoxine