BACKGROUND: The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients. RESULTS: HCU Network Australia is one of the very few support groups for patients with homocystinurias. Here we report the results of its survey of 143 patients and caregivers from 22 countries, evaluating current diagnostic pathways and management for the homocystinurias. Most (110) of the responses related to patients with CBS deficiency. The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1 year of the initial symptom but in 12.5% it took over 15 years. The delay was attributed mainly to ignorance of the disease. Physicians need to learn to measure homocysteine concentrations in children with neurodevelopmental problems, and in patients with heterogeneous symptoms such as thromboembolism, dislocation of the optic lens, haemolytic uraemic syndrome, and psychiatric disease. Even when the diagnosis is made, the way it is communicated is sometimes poor. Early-onset CBS deficiency usually requires a low-protein diet with amino acid supplements. More than a third of the participants reported problems with the availability or cost of treatment. Only half of the patients always took their amino acid mixture. In contrast, good adherence to the protein restriction was reported in 98% but 80% said it was hard, time-consuming and caused unhappiness. CONCLUSIONS: There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes.

Department of Paediatrics Landeskrankenhaus Bregenz Bregenz Austria

Department of Pediatrics and Inherited Metabolic Disorders Charles University 1st Faculty of Medicine General University Hospital Prague Czech Republic

Department of Psychosomatics and Psychiatry and Children's Research Center University Children's Hospital Zurich Zurich Switzerland

Division of Child and Adolescent Health Psychology Department of Psychology University of Zurich Zurich Switzerland

Division of Evolution and Genomic Sciences Institute of Human Development University of Manchester Manchester UK

Division of Metabolism and Children's Research Center University Children's Hospital Zurich Zurich Switzerland

HCU Network Australia Baulkham Hills Australia

Willink Metabolic Unit Manchester Centre for Genomic Medicine Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK

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