In inherited metabolic diseases, the final diagnosis is generally made by classic biochemical methods, despite the monogenic etiology. In lysosomal storage disorders, the suspected clinical diagnosis is confirmed by enzyme assay, and DNA analysis is not mandatory for the diagnosis or initiation of the treatment. Like in most enzyme deficits, the inheritance is recessive (autosomal or X-linked). Genetic heterogeneity is characteristic, and hundreds of alleles of the same gene may exist, caused by various mechanisms or mutations at different nucleotide levels. Besides the targeted analysis of the most frequent mutations (N370S, L444P, R463C, 84GG, recNciI, recTL) in Gaucher disease carried out in the national diagnostic center, often mutation scanning and sequencing is required. Though data must be carefully interpreted, molecular testing may provide important additional information, and it is the basis of carrier testing and prenatal diagnosis. The genotype-phenotype correlation remains inconclusive in most of the cases, though sometimes it can be used as a prognostic marker.