Clinical Characteristics, Molecular Background, and Survival of Egyptian Patients With Gaucher Disease Over a 20-Year Follow-up

Abstract

This study analyzes the general disease characteristics, impact of enzyme replacement therapy (ERT), and overall survival (OS) of 156 Egyptian patients with Gaucher disease (GD) enrolled on hormone replacement from 1998 to 2017. The mean age at diagnosis was 32.46 ± 12.68 months. Anemia was noted at diagnosis in 50%, thrombocytopenia in 30.7%, severe splenomegaly in 58.7%, severe hepatomegaly in 11.9%, and skeletal findings were detected in 24.3% of the patients. The most prevalent GD type was type 3 (54.5%). Twenty-two of type 3 patients had no neurological manifestations at diagnosis, and 12 developed variable central nervous system manifestations during follow-up. The most common neurological features were limited eye movements, oculomotor apraxia, and squint. Of the 60 patients for whom genotypes were obtained, homozygous L444P was the most common (n = 35/60, 58.3%). Treatment with ERT (imiglucerase) revealed significant improvements in blood indices, organ volumes, and growth parameters (P < 0.05). Ten (11.7%) type 3 patients did not develop any neurological manifestations under ERT over 20 years. Mortality was 16%, and the 20-year OS was 73.3%. We conclude that in Egypt, type 3 is the most prevalent phenotype of GD, and homozygous L444P is the predominant GBA genotype of GD. Early age at diagnosis and treatment with ERT over 20 years revealed significant improvements in disease manifestations, with an OS of 73.3%.

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach

“…In GD, the administered enzyme is taken up by the lysosome in the affected cell and helps to break down the accumulated substrate GlcCer 111 . Indeed, ERT has been shown to ameliorate the condition of various clinical manifestations of GD, including organomegaly, hematological abnormalities, and bone disease 113 . Besides, it has demonstrated improvements in quality of life and survival in GD patients 113 .…”

“…Indeed, ERT has been shown to ameliorate the condition of various clinical manifestations of GD, including organomegaly, hematological abnormalities, and bone disease 113 . Besides, it has demonstrated improvements in quality of life and survival in GD patients 113 . In 1991, ERT was introduced as a treatment for GD, which realized the vision initially proposed by Roscoe Brady in 1966 114 , 115 .…”

The D409H variant in GBA1: Challenges in predicting the Gaucher phenotype in the newborn screening era

“…We identified cases with D409H in concert with another second pathological variant in publications from China, Greece, Italy, Korea, Japan, and the United Kingdom (D'Amore et al, 2021; Dimitriou et al, 2020; El‐Beshlawy et al, 2022; Feng et al, 2018; Filocamo et al, 2002; Jeong et al, 2011; Tajima et al, 2009). There was one report of the genotype D409H/L444P in a patient with GD1 (Feng et al, 2018), but an additional eight cases with this genotype presented with GD3.…”