Expanding the phenotypic landscape of Gaucher disease type 3c with a novel entity - Transient neonatal cholestasis

Eur J Med Genet. 2023 Jun;66(6):104764. doi: 10.1016/j.ejmg.2023.104764.

PMID: 37061027

Fatma Derya Bulut, Deniz Kor, Sebile Kılavuz

Highlights: This descriptive study presents phenotypic heterogeneity and a novel clinical finding, transient neonatal cholestasis, among 13 patients with Gaucher disease (GD) type 3c.

Abstract

Background: Due to biallelic pathogenic mutations in the GBA gene, Gaucher disease (GD) is the most common lysosomal storage disorder. The Gaucher disease type 3c cardiovascular phenotype has only been linked to the homozygous D409H mutation.

Results: In this descriptive study, 13 patients with GD type 3c were shown to have phenotypic heterogeneity and a new clinical finding. Patients also had visceral (100%), hematological (92,3%), neurological (92,3%), and skeletal (30%) manifestations in addition to varied degrees of corneal opacities (76,9%) and heart valve and/or aortic calcifications (84,6%) and opacities. In terms of neurological involvement in GD type 3c, cervical dystonia (38,4%) and psychiatric problems (46,1%) were not uncommon phenomena. In this paper, a novel discovery in GD type 3c is highlighted, transient neonatal cholestasis (38,4%). Although transient neonatal cholestasis has not yet been documented in patients with GD, neonatal cholestasis is a condition associated with Gaucher type 2. From the severity of the disease or the age of commencement to the development of the disease, the clinical characteristics of GD type 3c are extremely diverse. Additionally, it is deduced that the age at which clinical symptoms first appeared may be related to the phenotypic range. Individuals who presented in infancy or childhood typically had visceral and hematological involvement, whereas individuals who presented in adolescence and adults typically had cardiac, neurological, and psychiatric behavioral abnormalities.

Conclusion: An adequate understanding of the pathogenesis may result from identifying the diverse clinical course of these people with this fatal condition, allowing for focused therapeutic interventions.

Keywords: Aortic calcification, Cardiac valve calcification, D409H, Gaucher disease type 3c, Transient neonatal cholestasis