Mucopolysaccharidosis type II - genotype/phenotype aspects

• Published in: Acta Paediatrica Vol. 91; no. s439; pp. 82 - 87
• Main Authors: Froissart, R, da Silva, I Moreira, Guffon, N, Bozon, D, Maire, I
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2002
• Subjects: Adolescent; Bone Marrow Transplantation; Child; Child, Preschool; DNA Mutational Analysis; enzyme replacement therapy; Female; Gene Expression Profiling; Genetic Heterogeneity; genetic studies; Genotype; Humans; Male; Mucopolysaccharidosis II - genetics; Mucopolysaccharidosis II - physiopathology; Mucopolysaccharidosis II - therapy; mucopolysaccharidosis type II; Phenotype; Severity of Illness Index
• ISSN: 0803-5253; 0803-5326; 1651-2227
• DOI: 10.1111/j.1651-2227.2002.tb03116.x

Establishing correlations between a patient's genotype and clinical phenotype is based on the assumption that the same clinical consequences will be observed in individuals with the same residual function of a specific metabolic step. In mucopolysaccharidosis type II (MPS II; Hunter disease), patients present with a wide clinical spectrum. Furthermore, current methods for measuring the activity of the deficient enzyme in MPS II – iduronate‐2‐sulphatase (IDS) – are insufficiently sensitive to differentiate between complete absence of activity and the presence of residual activity. Attempts have therefore been made to establish genotype‐phenotype correlations in order to explain the large degree of heterogeneity and to serve as a better guide to prognosis on which to base genetic counselling and treatment options. Using MPS II as an example, this paper illustrates the difficulties and potential advantages of determining genotype‐phenotype correlations in lysosomal storage diseases. The response of patients with MPS II to allogenic bone marrow transplantation provides some insight into the likely influence of certain genotypes on therapeutic efficacy. Conclusions: Evaluation of residual activity of IDS in MPS II using gene analysis, expression studies and transcript analysis does not always allow prediction of a patient's phenotype. The variable response to bone marrow transplantation, however, illustrates the potential importance of determining the genotype for selecting the most appropriate therapy for individual patients.