Niemann-Pick type B as ultra-rare differential diagnosis in hepatomegaly, steatohepatitis, low HDL and increased plasma chitotriosidase activity: three case reports

Introduction Niemann-Pick type B (NPB) is a usually benign lysosomal storage disorder, based on autosomal-recessively inherited deficient acid sphingomyelinase (ASM) activity, leading to accumulation of sphingomyelin in lipid-laden macrophages, coined NPB cells. Olipudase (Sanofi-Genzyme) has been shown to improve visceral manifestations and is currently being licensed as enzyme replacement therapy (ERT) for ASM deficiency.

Methods Two-center retrospective study of NP-B patients between 2014-2021.

Results Three patients were diagnosed with NP-B. Patient #1, female, *1962, had had posttraumatic splenectomy at age 22 and presented slightly hyperpnoic with mild hepatomegaly, total cholesterol (TC) of 254, LDL-C of 195 and HDL-C of 15 mg/dl. Chitotriosidase activity (CTA) was 4800 nmol/ml/h (ref. 10-150). On body plethysmography, carbon monoxide transfer factor (COTF) was 26 % of predicted. Pat. #2, male, * 1999, had hepatosplenomegaly, CTA of 3037 nmol/ml/h, spleen of 23 x 14 cm, low HDL and COTF of 49 %. Pat. #3, a female child, * 2011, showed hepatosplenomegaly and dyslipidemia. CTA and COTF were not available. All three diagnoses were confirmed by diagnostic molecular genetic testing. In addition to supportive therapies, initiation of ERT in the two adult patients is currently being established by an individual approach of the manufacturer.

Conclusion In all patients with hepatosplenomegaly, low HDL and increased CTA, NP-B should, besides Gaucher (GD) and cholesterol ester storage disease (CESD), be a differential diagnosis. Pulmonary CO transfer factor must necessarily be determined.

Publication History

Article published online:
26 January 2022