ABSTRACT
Introduction: Recommended by the National Advisory Council of the Disabled, the Ministry of Health of Singapore supported a nationwide study of inherited metabolic disorders (IMDs). When the 5-year project ended, investigations were provided as a diagnostic service. This paper documents our 13-year experience.
Materials and Methods: Patients with symptoms suggestive of an IMD were referred. Investigations on heparinised blood and/or urine included amino acid analysis using a Beckman 6300 Amino Acid Analyser, organic acids analysis using a Hewlett-Packard gas chromatography and mass spectrometry, mucopolysaccharides quantitative assay and high-resolution electrophoresis, sugars by thin-layer chromatography. Results: Of the 3656 patients studied from 1992 to 2005, IMDs were found in 127 (77 males; 50 females; age range, 1 day to 56 years). Their ethnic distribution was: 55.1% Chinese, 19.7% Malays, 11.0% Indians, 11.0% other races and 3.2% unknown. IMD diagnosed comprised 41 (32.3%) organic acidurias, 34 (26.8%) amino acidaemias/acidurias, 14 (11.0%) urea cycle defects, 15 (11.8%) mucopolysaccharidoses, 6 (4.7%) carbohydrate disorders and 17 (13.4%) others. Twenty-three (18.1%) cases were diagnosed during the neonatal period and 36 (28.3%) after the age of 13. Conclusion: Positive detection rate was 3.5% and 48 IMDs were found. Significant proportion of cases had late-onset IMDs. Early identification of IMDs permits timely management, genetic counselling and prenatal diagnosis.Inborn errors of metabolism (IEMs) described in the early 1900s by Garrod were due to a block in a metabolic pathway, arising from an enzyme deficiency which led directly to the disruption of cellular metabolism. However 40 years later, it was discovered that many inherited diseases were not due to a block in a metabolic pathway but caused by abnormality of a transport process affecting movement of specific metabolites within the vascular compartment, within the cell and across the cell membrane: uptake into the cells may be altered by a defect in a membrane receptor.
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