Abstract
AbstractGaucher disease (GD), which is due to a deficiency in the lysosomal enzyme β-glucocerebrosidase, is a rare genetic disorder. It is characterized by a wide variety of clinical manifestations and severity of symptoms, making it difficult to manage. A cross-sectional hospital-based genetic study was undertaken with 32 pediatric patients. We recruited 21 males and 11 females diagnosed with GD, with a male-to-female ratio of 1.91:1. The mean age of the study population was 8.79 ± 4.37 years with an age range from 8 months to 17 years. We included patients on clinical evaluation from 2011 to 2019. An enzyme assay test was used to measure β-glucosidase enzyme activity in leukocytes and the GBA gene study was performed by polymerase chain reaction technique. We found GD type 1 in 27 (84.37%) participants, GD type 3 in five (15.63%) participants, while none classified as GD type 2. The dominant mutation in GD 1 was N370S in 81.5%, of which two-thirds were homozygous. The second common mutation in this type of disease (L444P) was present in nine cases (40.9%), two of whom were homozygous (9.9%). Meanwhile, R463C was present in six cases (27.27%), of whom one was homozygous. In GD 3, the dominant mutation was L444P as seen in 80% of the patients followed by N370S and R463C in 20%. This study shows that the most common mutant allele in this study was N370S, followed by L444P. Further large-scale studies with more advanced designs are recommended to explore the sequences of GBA genes.
Highlights
Gaucher disease (GD), though the most common lysosomal storage disease, is a rare disease, with a worldwide prevalence of 1 in 75,000 live births.[1,2] It is the commonest genetic disease among Jewish populations, especially among Ashkenazi Jews.[3]
We found GD type 1 in 27 (84.37%) participants, GD type 3 in five (15.63%) participants, while none classified as GD type 2
GD is inherited as an autosomal recessive disorder resulting from pathogenic mutations of the GBA gene encoding the enzyme glucocerebrosidase, located on chromosome 1.q21.31
Summary
Gaucher disease (GD), though the most common lysosomal storage disease, is a rare disease, with a worldwide prevalence of 1 in 75,000 live births.[1,2] It is the commonest genetic disease among Jewish populations, especially among Ashkenazi Jews.[3]. The commonest associated clinical features include hepatosplenomegaly, thrombocytopenia, anemia, and bone involvement. Patients may develop bone pain, pathologic fractures, and joint collapse as a result of progressive infiltration of Gaucher cells in the bone and bone marrow. Avascular necrosis of the bone occurs in about one-third of patients, eventually leading to irreversible bone destruction. The rapid detection of bone involvement by diffusion-weighted MR imaging is important as skeletal changes can be reversible at an early stage.[5] There are both non-neuronopathic (type 1; OMIM 230800) and neuronopathic (types 2 and 3; OMIMs 230900 and 231000) forms of the disorder.[6] received July 15, 2020 accepted October 5, 2020
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