A case report on three family members with Gaucher disease (GD) underlines the importance of early diagnosis and treatment with enzyme replacement therapy (ERT) to prevent disease progression and improve quality of life.
Researchers also call for doctors to consider GD screening for relatives of patients diagnosed with the disease.
Treatment goals for available GD therapies include easing symptoms and preventing the severity of complications. The major aim is to improve the patients’ quality of life and reduce the disease impact in patients’ daily lives.
The main treatment options for GD are ERT — administration of a functional glucosylceramidase, the enzyme missing in GD — and, for some patients, substrate reduction therapy (SRT) — which degrades glucocerebroside, the fatty molecule that builds up in GD.
Previously, it was reported that although ERT was relieved GD symptoms, response to the treatment “was reduced in presence of massive splenomegaly [spleen enlargement], irreversible bone damage, liver disease or hepatopulmonary syndrome at presentation,” the researchers noted.
The relatives were all males, ages 17, 46, and 51, and were referred to the Faculty of Medicine, Celal Bayar University or the Malatya State Hospital, both in Turkey.
At referral, all patients presented with an enlarged spleen, or splenomegaly, and/or liver, or hepatomegaly, which made the doctors suspect a GD diagnosis. Enzymatic testing (a blood test used to diagnose GD) revealed a deficiency in glucosylceramidase, and a genetic screen identified mutations in the GBA gene, the gene that provides instructions for the production of glucosylceramidase, confirming the diagnosis of GD.
None of the subjects had neurological symptoms; one patient had bruising problems, another had bone pain and nose bleeding, and another complained of fatigue and pain in the knee and hip.
Upon diagnosis, all patients started intravenous infusions of Cerezyme, given as 30 or 60 units per kilogram every two weeks.
After the first year of treatment, Cerezyme relieved symptoms in all patients, including lessening spleen and liver size, and decreasing pain, bruising, and nosebleeds. Alleviating these symptoms helped improve the patients’ quality of life.
Treatment also improved the levels of blood platelets, white blood cells, and hemoglobin (the carrier protein of oxygen in red blood cells and a marker of anemia), bringing them closer to normal.
In the youngest patient, blood platelet counts were raised by 25% and white blood cells were 30% decreased. Contrary to the other two, this patient had high white blood cells before treatment.
In the 46-year-old patient, hemoglobin was increased 10%, white blood cells 30% and platelets 90%. In the oldest, hemoglobin and white blood cells increased 10%, while blood platelets decreased 20%.
In the oldest patient, treatment was not able to heal any bone deterioration, seen on radiography, suggesting his bone problems were irreversible; however, he did report a slight relief in pain.
Based on the observed cases, researchers say that ERT is able to revert symptoms, but stress it is particularly effective if given at an early stage of the disease.
“Early diagnosis leads to early treatment and prevents, particularly in patients with massive splenomegaly and irreversible changes, disease progression,” they wrote.
Emphasizing the importance of early interventions in GD, they add that when “organomegaly [organ enlargement] and irreversible bone changes occurs, not only deterioration in the quality of life and symptoms, but reduction in treatment response is also observed.”
In this sense, raising awareness of the disease and conducting research on more therapeutic options, such as gene therapy and ways to enhance enzyme activity, will be important.