Most Filipino patients with Gaucher disease carry severe mutations in the GBA gene and exhibit Gaucher disease type 3, researchers from the Philippines found.
The study, “Genetic and clinical characteristics of Filipino patients with Gaucher disease,” was published in the journal Molecular Genetics and Metabolism Reports.
Gaucher disease (GD) is a genetic condition caused by abnormal production of an enzyme called beta-glucocerebrosidase, which degrades a fat substance called glucocerebroside.
Glucocerebroside accumulates in several organs, but the disease mostly affects the liver, spleen, bone marrow, and nervous system.
Beta-glucocerebrosidase is coded in the genome by the GBA gene; mutations in this gene usually drive the condition. The severity of the mutations influences the severity of symptoms.
A number of mutations in the GBA gene have been identified, with researchers finding that some are specific to certain nationalities. Thus, recognizing which mutations are most likely to appear in a certain population could improve genetic testing approaches and understanding of the disease and its course in people who develop the condition.
To understand the most prevalent mutations and clinical features associated with GD in the Philippines, researchers reviewed medical records of 14 patients (three men and 11 women).
Patients had started experiencing symptoms between the ages of 1 and 2. Overall, there was an average 2.2-year gap between the onset of clinical symptoms and GD diagnosis.
Of the 14 patients, one woman was of Indian origin and one man was Filipino/Japanese. The remaining 12 patients were Filipino.
In this study population, five patients had type 1 disease with no brain involvement; two patients had type 2 disease. The remaining seven were classified as GD type 3 because they experienced seizures, delay in development, and irregular eye movements.
The swelling of liver and spleen — hepatosplenomegaly — was the most common clinical symptom in this population (85.7%), followed by impaired growth (64.3%), and bone abnormalities (63.6%). The team also reported anemia and low platelet count in most patients.
Only six patients in this study received enzyme replacement therapy (ERT) to restore the function of the glucocerebrosidase enzyme. Four of those patients achieved normal platelet levels, the study reported. Similarly, ERT decreased swelling of the liver and spleen in four patients. However, no improvement was noted in growth, bone abnormality, or neurological symptoms after ERT.
Researchers found that the most severe GBA mutation — L483P — was the most commonly detected in this study group. Other severe mutations, such as F252I, G241R, G416S, R159W and IVS2 + 1 G > A, were also detected. These mutations caused clinical symptoms associated with type 2 and type 3 GD, the researchers said.
Two new mutations — N131S and D257V — were identified; they were both found in patients with type 2 and type 3 GD. The mutant allele N131S has only been reported in Filipinos, strengthening its association with this population.
“With the recent passage of the Rare Disease Act of the Philippines, it is hoped that physicians will be more aware of the presenting signs and symptoms of GD so that better access to diagnosis, and provision of a more comprehensive and sustainable treatment and monitoring will improve the neurologic and non-neurologic complications of the disease in this population,” the team concluded.