DEFICIT LYZOZOMALNI SFINGOMYELINAZY: SPEKTRUM FENOTYPU U ČESKÝCH A SLOVENSKÝCH PACIENTŮ

Deficit of Lysosomal Sphingomyelinase Phenotype Spektrum of the Czech and Slovak Patients

Background.
We present a series of 25 patients (from 21 families) with deficiency of lysosomal sphingomyelinase (acid sphingomyelinase, ASM), diagnosed during the last 30 years.Methods and Results. Diagnosis was established by finding specific sphingomyelin storage pattern in bone marrow histiocytes and in some bioptical and postmortem tissues (presence of sphingomyelin liquid crystals) and finaly by proving ASM deficiency in white blond cells and in cultured fibroblasts.Range of clinical manifestations of our patients notably exceeded the the known main (A,B) phenotypes described so far. In the group of type A patients (clinically overt neurovisceral symptomatology) there was significant tendency to prolonged course. Classical fulminant course with death between 5 to 45 months of age was seen only in a subgroup. . of 5 patients. In other type A patients (n=8) the course was prolonged attaining 5 years of age, the end of the hrst (8, and 9 years), second (14, 17 years), third (22 years), fourth (32 years) and fifth decades (41 years). Three of these patients (aged 5, 22 and 41 years) are living. The series of patients with dominant visceral involvement (n=12) consisted of three phenotypically different subgroups. One with chronic purely visceral affection and prolonged course (n=4) corresponding to the classical type B, the second with chronic course and largely subclinical neurological affection (n=4) and the third with accelerated fatal visceral affection (death in age range 31 months - 9 years) without (n=1) or with clinically minor signs of brain damage (n=3).Conclusions. Study of the presented series of ASM deficient patients disclosed remarkable phenotypical variability. Two main factors seem to be responsible. Variability in the storage intensity in the two main tissue compartments (neuronal and visceral), and the absence of proportionality in their affection in some instances. The described phenotype variability enlarges significantly the known spectrum of phenotypes in ASM deficiency.

Key words:
Niemann-Pick disease, acid sphingomyelinase deficiency, phenotype varibility.