Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up

Orphanet J Rare Dis. 2019 Feb 22;14(1):55. doi: 10.1186/s13023-019-1029-1.


Background: Acid sphingomyelinase deficiency (ASMD), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is divided into infantile neurovisceral ASMD (Niemann-Pick type A), chronic neurovisceral ASMD (intermediate form, Niemann-Pick type A/B) and chronic visceral ASMD (Niemann-Pick type B). We conducted a long-term observational, single-center study including 16 patients with chronic visceral ASMD.

Results: 12 patients were diagnosed in childhood and 4 others in adulthood, the oldest at the age of 50. The mean time of follow-up was approximately 10 years (range: 6 months - 36 years). Splenomegaly was noted in all patients at diagnosis. Hepatomegaly was observed in 88% of patients. Moderately elevated (several-fold above the upper limit of normal values) serum transaminases were noted in 38% of patients. Cherry-red spots were found in five Gypsy children from one family and also in one adult Polish patient, a heterozygote for p.delR610 mutation. Dyslipidemia was noted in 50% of patients. Interstitial lung disease was diagnosed in 44% of patients. Plasmatic lysosphingomyelin (SPC) was elevated in all the patients except one with p.V36A homozygosity and a very mild phenotype also presenting with elevated plasmatic SPC-509 but normal chitotriosidase activity. The most common variant of SMPD1 gene was p.G166R. We found a previously unreported variant in exon 2 (c.491G > T, p.G164 V) in one patient.

Conclusions: Chronic visceral ASMD could constitute a slowly progressing disease with a relatively good outcome. The combined measurement of lysosphingomyelin (SPC) and lysospingomyelin-509 (SPC-509) is an essential method for the assessment of ASMD course.

Keywords: Acid sphingomyelinase; Chitotriosidase; Chronic visceral acid sphingomyelinase deficiency; Hepatosplenomegaly; Lysosphingomyelin; Lysosphingomyelin-509.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Hexosaminidases / genetics
  • Hexosaminidases / metabolism
  • Homozygote
  • Humans
  • Infant
  • Male
  • Mutation / genetics
  • Niemann-Pick Disease, Type A / genetics
  • Niemann-Pick Disease, Type A / metabolism*
  • Poland
  • Sphingomyelin Phosphodiesterase / genetics
  • Sphingomyelin Phosphodiesterase / metabolism*
  • Young Adult


  • Sphingomyelin Phosphodiesterase
  • Hexosaminidases
  • chitotriosidase