A bone marrow transplant successfully reduced the severe lung involvement that developed in a 5-year-old boy with Gaucher disease who was receiving enzyme replacement therapy (ERT), a study reported.
The boy was described in a previous report as the youngest patient with the heritable disease to develop benign accumulations of so-called Gaucher cells — called Gaucheroma — after starting ERT.
The latest report, “Allogeneic hematopoietic stem cell transplantation for treating severe lung involvement in Gaucher disease,” was published in the journal Molecular Genetics and Metabolism Reports.
Diagnosed with Gaucher at 17 months, the patient had promptly begun ERT every two weeks. His condition initially improved, with increased hemoglobin — the oxygen-carrying protein in red blood cells — and platelet levels, and a reduction in the enlargement of both his liver and spleen, which is an early and the most common symptom of Gaucher.
However, Gaucheroma was identified in his liver 19 months (just over 1.5 years) into the treatment. A subsequent increase in ERT dosage did not decrease Gaucheroma size after eight months and the dose was reverted back to the standard 60 international units/kg (IU/kg).
Nearly four years into his ERT treatment, the boy began to develop respiratory symptoms, including a persistent cough and rapid breathing. A chest X-ray revealed infiltration of Gaucher cells in the lungs that progressed rapidly. Of note, Gaucher cells result from immune cells called macrophages accumulating a fatty substance called glucocerebroside due to a mutation in the GBA gene.
Four months after lung involvement was discovered, the patient received an allogeneic hematopoietic stem cell transplant (HSCT) — a bone marrow transplant from a matched, unrelated donor.
Within one month of the transplant, his respiratory symptoms had subsided. The lung infiltration was reduced at three months and pulmonary function had improved at seven months. Restored levels of beta-glucocerebrosidase, the enzyme that is deficient in Gaucher disease, also suggested a reduction in disease activity. The Gaucheroma in the liver were unaffected by the transplant.
“Based on our patient, we suggest that allogeneic HSCT should be considered as a treatment option for patients with rapidly progressive, severe infiltrative lung involvement who have already received standard or higher doses of ERT,” the research team wrote.
The scientists also reported that the boy’s younger brother, identified as patient B, carried the same Gaucher disease-causing mutation and had decreased beta-glucocerebrosidase levels at birth. He began receiving ERT at nine months due to his low hemoglobin and platelet levels.
Similar to his older brother, patient B exhibited lung involvement along with abnormal enlargement of the spleen and liver 30 months into treatment. However, no Gaucheroma were identified. ERT treatment was increased to 100 IU/kg every two weeks, resulting in a slight reduction in lung infiltration. Interestingly, patient B never exhibited respiratory symptoms.
“Based on the experiences of our patients and literature review, regular chest imaging follow up for both symptomatic and asymptomatic patients, possibly biannual chest X-rays, might be helpful for Gaucher disease management,” the researchers added.
