Clinical, Enzymatic, and Molecular Diagnosis of Mucopolysaccharidoses (MPSs) in Iran

Mucopolysaccharidoses are a group of rare mostly autosomal recessivemetabolic and genetic disorders. Because of the high rate of consanguinity,they are not uncommon in our population. They are genetic disorders, andnow most of the responsible genes were determined, mapped, and cloned.Common mutations in different ethnic groups are being discovered. Clinicaldiagnosis is not difficult for experienced physicians, but for treatment, andprevention measures in the future pregnancies precise biochemical ormolecular diagnosis is mandatory.It is necessary to detect the type of MPS by measurement of responsibleenzyme activity in the leukocytes and fibroblasts. Whenever we determinedthe exact type of the MPS by enzyme assay, we would be able to treat thepatients with the different therapeutic options, like enzyme replacementtherapy(ERT), bone marrow transplantation(BMT), stem celltransplantation(SCT), or even gene therapy in the near future.In the past 2 decades more than 240 families with 311 patients were referredfor diagnosis and confirmation. After gathering necessary informationregarding the probands and the families, and constructing detailed familytrees, we evaluated the cases comprehensively by clinical and XR examination.If the phenotype of the patient was suggestive for one of MPSs, urine GAGswere positive, and XR exam showed Dysostosis Multiplex Congenita(DMC),then we arranged to investigate enzyme analysis for the suspected phenotype.We detected 64 families with type IIIMPS, followed by 56 families with type II,and 39 familes with type VI respectively. We also have seen 38 families withtype I, and 37families with type IV.At present, wild type or normal enzymes for MPSs type I, II, and VI are beingproduced by recombinant DNA technology. Enzymes for these types now areapproved following extended clinical trials, are safe and efficient and alleviatemany systemic signs and symptoms of these diseases. There are some difficulties regarding the marketing and high cost of theavailable enzymes in our population. If public health responsibilities andinsurance companies support the families financially there is not any problemto use enzymes in our patients in Iran. Some of our patients have been treatedby BMT, and the results would be released in the conference. Also we shouldconsider other therapeutic modalities, like stem cell transplantation, or evengene therapy for the future. Now our priority is to do prenatal testing anddetect affected fetuses by enzyme assay or molecular analysis on fetal cellsafter amniocentesis or CVS. We think that termination of the affected fetuses islogical option to control and prevent this type of very unfortunate disorders.

Keywords:

MPS , Enzyme assay , Enzyme replacement , Gene therapy