Inherited metabolic diseases: Advances in delineation, diagnosis, and treatment

Recent advances have been made in the delineation, diagnosis, and treatment of several inborn errors of metabolism. In certain of these disorders the clinical recognition of variants has led to the discovery of new enzymatic defects which illustrate the extensive interallelic heterogeneity which may occur within a phenotype. Specific metabolic defects have been identified in the atypical hyperphenylalaninemias and in the multiple carboxylase deficiency diseases. The enzymatic defects have been identified in several lysosomal storage diseases, including mucolipidoses II, III, and IV. A fourth distinct enzymatic defect has been identified as a cause of mucopolysaccharidosis III. In addition, cystinosis has been shown to result from the defective lysosomal transport of cystine. Improved diagnostic techniques which use restriction endonucleases, hybridoma antibodies or high-performance liquid chromatography have been developed. Implementation of these techniques should add increased sensitivity, specificity, and rapidity to our diagnostic armamentarium. New approaches for the treatment of certain disorders have been based on increased understanding of their molecular pathology and/or metabolic derangements.