Lysosomal enzyme deficiencies may be sought in serum or plasma, in leukocytes (white cell pellet) or in cultured fibroblasts.
Although it is evident that there is great variation in the severity of the neurological disorders which may result from a severe lysosomal enzyme deficiency, extreme caution is necessary when partial deficiency is found, particularly 'within the heterozygous range', since in some of these disorders the prevalence of heterozygosity is quite high in the normal population.
The term 'pseudodeficiency' is used in lysosomal storage diseases to denote the situation in which individuals show greatly reduced enzyme activity but remain clinically healthy. Pseudodeficiencies have been reported for several lysosomal hydrolases. Pseudodeficiency is particularly important in relation to arylsulphatase A (ARSA), which is the enzyme classically deficient in metachromatic leukodystrophy (MLD). In pseudo-MLD, patients will not have the appropriate clinical features, and although they have ARSA levels of 10-15% of the normal mean, they do not have excess urinary sulphatides or toluidine blue staining metachromatic granules in urine (second morning specimen).