Researchers report rare GBA1 variant in man with type 1 Gaucher disease
Single-patient case study explores clinical and biochemical features
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Researchers have reported the case of a young man with type 1 Gaucher disease caused by a rare mutation in the GBA1 gene, which may help explain how this mutation affects the disease and response to treatment.
The mutation, known as p.Thr82Ile, was found in both copies of the man’s GBA1 gene, a genetic combination that has not been widely studied in people with Gaucher disease.
Case report offers insight into a rare GBA1 variant
By describing the patient’s symptoms, laboratory findings, and response to therapy, the study offers insight that may help improve diagnosis and genetic counseling.
The case was described in the study, “Homozygous GBA1 p.T82I variant in type 1 Gaucher disease: clinical and biochemical characterization,” published in Personalized Medicine.
Gaucher disease is caused by mutations in the GBA1 gene that reduce the activity of glucocerebrosidase (GCase), an enzyme that helps break down certain fatty molecules.
As a result, these fats accumulate, particularly in immune cells called macrophages, forming so-called Gaucher cells. These cells can build up in organs such as the liver, spleen, and bone marrow, leading to many of the disease’s symptoms.
More than 400 different GBA1 mutations are known to cause Gaucher disease. While there isn’t a clear connection between specific mutations and how the disease will progress, researchers know that some mutations are more often linked to more severe disease or neurological symptoms.
This means that knowing which mutations a person carries can sometimes help guide care decisions and genetic counseling. However, many mutations are rare, and doctors may have limited information about how they affect symptoms or response to treatment.
Researchers describe a single Gaucher disease case
Now, researchers in Turkey described the case of a 23-year-old man with Gaucher disease type 1 caused by a rare mutation in both copies of the GBA1 gene.
The man was referred for evaluation after experiencing fatigue and chills for about three months, followed by bone pain that began about six weeks before his hospital visit.
Initial tests showed low platelet levels and an enlarged spleen and liver, all common features of Gaucher disease. A bone marrow biopsy confirmed the presence of Gaucher cells, supporting the diagnosis.
Further testing showed that GCase activity in the patient’s immune cells was markedly reduced, while blood levels of glucosylsphingosine (lyso-Gb1), a key biomarker of Gaucher disease, were elevated. The patient was also found to have reduced bone density.
Genetic analysis identified the p.Thr82Ile mutation in both copies of the GBA1 gene. While this variant has been reported previously and is listed as disease-causing in some genetic databases, little has been known about how it affects symptoms, laboratory markers, or disease course.
The researchers conducted genetic screening of the patient’s family members. This revealed that his parents and sister each carried one copy of the p.Thr82Ile mutation but had normal GCase activity and no symptoms of Gaucher disease, while his brother did not carry the mutation.
Treatment led to clinical and laboratory improvement
Based on these results, the man was diagnosed with type 1 Gaucher disease and began enzyme replacement therapy with Cerezyme (imiglucerase). After three months of treatment, the patient experienced a clear improvement in symptoms, particularly less fatigue and bone pain. At a six-month follow-up, platelet counts had increased into the normal range, liver and spleen sizes were smaller, and bone density had improved.
“Our report presents the first comprehensive characterization of this variant” in a patient with the mutation in both copies of the gene, the researchers wrote, adding that the data support the classification of this mutation as “likely pathogenic” under specific guidelines.
“Early detection of pathogenic variants also informs therapeutic decision-making,” they concluded. “Thus, characterization of rare GBA1 variants contributes directly to personalized medicine by improving risk assessment, prognosis, family counseling, and individualized treatment planning.”
