Splenomegaly and progressive neurologic involvement: Think about Niemann-Pick type C disease.

BACKGROUND

Niemann-Pick type C (NPC) disease is a lysosomal storage disease with visceral organ involvement and neurological and psychiatric symptoms. This study presents the clinical and laboratory findings of NPC cases involving three novel variants.

METHODS

The clinical and laboratory findings were reviewed retrospectively between February 2006 and December 2022.

RESULTS

There were nine females and five males. The median age of diagnosis of the patients was 5 months (range: 1 month to 38 years). The clinical phenotypes of the patients were early infantile (n = 7), late infantile (n = 4), juvenile (n = 2), and adult (n = 1). The visceral findings were splenomegaly (100%), hepatomegaly (78.6%), neonatal jaundice (42.8%), and hepatic failure (14.3%). The neurological findings were developmental delay (71.4%), seizures (50%), vertical supranuclear gaze palsy (28.6%), ataxia (28.6%), dysarthria (28.6%), dysphagia (21.4%), dystonia (21.4%). Cataplexy (14.3%) and psychiatric manifestations (14.3%) were recorded in juvenile and adult-onset patients. Three novel variants were detected (p.Asn524LysfsTer39, p.Val1023Phe, and p.Asn906Tyr). Miglustat treatment was received by 64.3% of patients but had no clear effect on the disease course. The median duration of use was 3 years (with a range from 1-13 years). Miglustat's adverse effects were low platelet count (35.7%) and diarrhea (7.1%).

CONCLUSIONS

Niemann-Pick type C disease should be considered in the presence of visceral organ involvement and progressive neurological findings. It is essential to support the diagnosis with laboratory and genetic analysis.