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      Lysosomal storage disorders: Molecular basis and laboratory testing

      review-article
      1 , , 2
      Human Genomics
      BioMed Central

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          Abstract

          Lysosomal storage disorders (LSDs) are a large group of more than 50 different inherited metabolic diseases which, in the great majority of cases, result from the defective function of specific lysosomal enzymes and, in cases, of non-enzymatic lysosomal proteins or non-lysosomal proteins involved in lysosomal biogenesis. The progressive lysosomal accumulation of undegraded metabolites results in generalised cell and tissue dysfunction, and, therefore, multi-systemic pathology. Storage may begin during early embryonic development, and the clinical presentation for LSDs can vary from an early and severe phenotype to late-onset mild disease. The diagnosis of most LSDs--after accurate clinical/paraclinical evaluation, including the analysis of some urinary metabolites--is based mainly on the detection of a specific enzymatic deficiency. In these cases, molecular genetic testing (MGT) can refine the enzymatic diagnosis. Once the genotype of an individual LSD patient has been ascertained, genetic counselling should include prediction of the possible phenotype and the identification of carriers in the family at risk. MGT is essential for the identification of genetic disorders resulting from non-enzymatic lysosomal protein defects and is complementary to biochemical genetic testing (BGT) in complex situations, such as in cases of enzymatic pseudodeficiencies. Prenatal diagnosis is performed on the most appropriate samples, which include fresh or cultured chorionic villus sampling or cultured amniotic fluid. The choice of the test--enzymatic and/or molecular--is based on the characteristics of the defect to be investigated. For prenatal MGT, the genotype of the family index case must be known. The availability of both tests, enzymatic and molecular, enormously increases the reliability of the entire prenatal diagnostic procedure. To conclude, BGT and MGT are mostly complementary for post- and prenatal diagnosis of LSDs. Whenever genotype/phenotype correlations are available, they can be helpful in predicting prognosis and in making decisions about therapy.

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          Most cited references56

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          Functions of lysosomes.

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            The cell biology of lysosomal storage disorders.

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              The frequency of lysosomal storage diseases in The Netherlands.

              We have calculated the relative frequency and the birth prevalence of lysosomal storage diseases (LSDs) in The Netherlands based on all 963 enzymatically confirmed cases diagnosed during the period 1970-1996. The combined birth prevalence for all LSDs is 14 per 100,000 live births. Glycogenosis type II is the most frequent LSD with a birth prevalence of 2.0 per 100,000 live births, representing 17% of all diagnosed cases. Within the group of lipidoses, metachromatic leukodystrophy (MLD) is the most frequent LSD. MLD was diagnosed in 24% of lipidoses and the calculated birth prevalence was 1.42 per 100,000 for all types combined. Krabbe disease, diagnosed in 17% of cases, also belongs to the more frequent lipid storage diseases in The Netherlands with a birth prevalence of 1.35 per 100,000. The birth prevalence of Gaucher disease, commonly regarded as the most frequent lipid storage disease is 1.16 per 100,000 for all types combined. The combined birth prevalence for all lipid storage diseases is 6.2 per 100,000 live births. Within the group of mucopolysaccharidoses (MPSs), MPS I has the highest calculated birth prevalence of 1.19 per 100,000 (25% of all cases of MPS diagnosed), which is slightly more frequent than MPS IIIA with an estimated birth prevalence of 1.16 per 100,000. As a group, MPS III comprises 47% of all MPS cases diagnosed and the combined birth prevalence is 1.89 per 100,000 live births. The birth prevalence of MPS II is 0.67 per 100,000 (1.30 per 100,000 male live births). All other MPSs are rare. The combined birth prevalence for all MPSs is 4.5 per 100,000 live births. Mucolipidoses and oligosaccharidoses are very rare with birth prevalences between 0.04 and 0.20 for individual diseases. Only 49 cases were diagnosed between 1970 and 1996. Their combined birth prevalence is 1.0 per 100,000 live births.
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                Author and article information

                Journal
                Hum Genomics
                Hum. Genomics
                Human Genomics
                BioMed Central
                1473-9542
                1479-7364
                2011
                1 March 2011
                : 5
                : 3
                : 156-169
                Affiliations
                [1 ]S.S.D. Lab. Diagnosi Pre-Postnatale Malattie Metaboliche, Dipartimento di Neuroscienze, IRCCS G. Gaslini, Largo G. Gaslini 5, Genova, Italy
                [2 ]Metabolic and Muscular Unit, Clinic of Pediatric Neurology, Department of Sciences for Woman and Child's Health, University Florence, Meyer Children's Hospital, Viale Pieraccini n. 24, 501329 Florence, Italy
                Article
                1479-7364-5-3-156
                10.1186/1479-7364-5-3-156
                3500170
                21504867
                95a27d8d-c203-4e81-b04d-c75d7b3202de
                Copyright ©2011 Henry Stewart Publications
                History
                : 7 January 2011
                : 7 January 2011
                Categories
                Review

                Genetics
                Genetics

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