Patients with Gaucher disease type 1 who never received treatment with enzyme replacement therapy died of septicemia — a blood infection — nine times more often than the general population, followed by liver disease, suicide or drug overdose, and cancer.
Cancer, however, was the most common cause of death in these patients.
The U.S. study, “Causes of death in 184 patients with type 1 Gaucher disease from the United States who were never treated with enzyme replacement therapy,” was published in the journal Blood Cells, Molecules And Diseases.
Gaucher disease type 1 (GD1) is a hereditary condition caused by defects in the glucocerebrosidase enzyme, which is required to break down the fatty molecule glucocerebroside. This results in the accumulation of glucocerebroside in multiple organs, especially the liver and the spleen.
Although GD1 affects people of all ethnicities, it is most commonly seen in people of Ashkenazi Jewish descent, affecting one in 450 people. Prompt treatment is essential to minimize the complications and lasting damage of GD1, such as blood infection.
While enzyme replacement therapy can lessen symptoms and improve outcomes for Gaucher patients, studies suggest they are at greater risk for other complications, including Parkinsonism, blood diseases, infection, and liver cancer, compared with the general population.
Researchers set out to investigate the causes of death in GD1 patients who had never received enzyme replacement therapy (ERT) or any other treatment for their condition.
They assessed the causes of death of 184 patients (111 men), who died between 1950 and 2010. Their median age at death was 66; of the 184, 67.4% were of Ashkenazi Jewish descent.
“Our population of untreated patients is a valuable historical control for studies of the effect of GD1 treatment on premature mortality,” the investigators wrote.
Using proportional mortality ratio (PMR), the team assessed the causes of death in these patients compared with the general U.S. population. A PMR greater than one indicates that more patients with Gaucher die from that condition than the general population.
Results showed that deaths from blood infection were nine times more frequent in Gaucher patients than the general population. But deaths from chronic liver disease, suicide or drug overdose, and cancer were also significantly higher in these patients.
Heart disease, cerebrovascular disease or stroke, and accidents were less frequent causes of death in these patients compared to the general population.
GD1 frequently manifests as the abnormal swelling of the liver and spleen. Surgical removal of the spleen (splenectomy) is often used to manage the condition.
In the study, 51.1% of patients had a splenectomy. In these patients, chronic liver disease, pulmonary hypertension, complications after spleen removal, and gastrointestinal bleeding were significantly more prevalent in the GD1 group.
“We anticipate that with earlier diagnosis, improved risk assessment and phase-out of splenectomy, plausibly avoidable causes of premature death observed in our study population should be increasingly rare with timely institution of appropriate treatment,” researchers wrote.