Understanding the relationship between genotype and clinical phenotype will
clearly aid in the prognosis, treatment and counselling of patients with l
ysosomal storage diseases (LSDs). This, however, will require the establish
ment of widely accepted indices with which to score the severity of LSDs, a
s these diseases are characterized by their marked clinical heterogeneity.
Even in the complete absence of a functional enzyme, presentation may be va
riable, depending on the patient's genetic background and on a range of epi
genetic and environmental factors. Further difficulties in predicting disea
se severity and progression from the genotype arise from the rarity of thes
e disorders, the low enzyme levels required for a normal phenotype and the
relative lack of understanding of the pathophysiology of LSDs.