Clinical and Laboratory Characteristics of Gaucher Disease Caused by Complex Heterozygous Mutation.

Background: This study aimed to investigate and review the clinical and laboratory characteristics of Gaucher disease type 1 (GD1) caused by the heterozygous mutation of the Glucocerebrosidase (GBA) gene.

Methods: In this study, the bone marrow smear and biopsy slice were observed using Wright-Giemsa as well as Hematoxylin and Eosin (HE) stains, respectively. Furthermore, peripheral blood leukocyte lysosomes were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The patient's and her parents' peripheral blood DNA were extracted, and the mutation sites of the GBA-related genes were sequenced via Sanger sequencing.

Results: It was revealed that the Gaucher cells in the bone marrow smear and biopsy slice had large volume, were round, ovoid or irregular, occasionally binucleated or multinucleated, with chromatin roughness and occasional nucleoli, rich in the cytoplasm, bluish or grayish-red colored, and with many cytoplasmic onion-skin-like striped structures. Furthermore, the expression of GBA was decreased, while glucosylsphingosine levels were elevated. Moreover, the patient had a heterozygous complex mutation in the GBA gene (GBA NM_001005741.2): c.1604G > Ap.Arg535Hi (R496H) from her mother and c.1448T > Cp. Leu483Pro (L444P) at chromosomal locations chr1:155204793 and chr1:155205043, respectively.

Conclusions: The results show that a heterozygous complex mutation of R496H and L444P in the GBA gene causes the development of GD1. Clinical, enzyme activity-based assays, biological markers, and genetic analysis can significantly improve disease diagnosis and are important for early intervention and GD treatment.