[Lysosomal sphingomyelinase deficiency: spectrum of phenotypes in 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.


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 finally by proving ASM deficiency in white blood 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 first (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.
Elleder
M
M
Ustav dĕdicných poruch metabolizmu 1. LF UK, Praha. melleder@beba.cesnet.cz
Poupĕtová
H
H
Ledvinová
J
J
Zeman
J
J
Rosipal
S
S
Kraus
J
J
D002648:Child; D002675:Child, Preschool; D018153:Czech Republic; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009542:Niemann-Pick Diseases / Q000145:classification / Q000175:diagnosis*; D010641:Phenotype; D018154:Slovakia; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency*
D013108:Sphingomyelin Phosphodiesterase