Boy with Gaucher disease develops complication despite ERT treatment
Case report highlights limitations of therapy in reaching lymph nodes
A 4-year-old boy with Gaucher disease developed enlarged lymph nodes and a serious digestive complication called protein-losing enteropathy (PLE), despite being on enzyme replacement therapy (ERT) since the first weeks of life, according to a recent case report.
While his symptoms improved with corticosteroid treatment and dietary changes, the case highlights the limitations of current ERT in reaching certain tissues, such as lymph nodes, as complications can develop even with early treatment.
This finding underscores the importance of close monitoring for new symptoms in people with Gaucher disease, and the urgent need for new therapies that can better target all affected areas of the body.
“Our case particularly underscores that even in patients receiving early treatment, [gastrointestinal] complications can emerge, emphasizing the urgent need for developing alternative, tailored therapeutic approaches to effectively manage these patients,” researchers wrote.
The study, “Early Enzyme Replacement Therapy Does Not Prevent the Protein Losing Enteropathy Syndrome in Neurovisceral Gaucher Disease,” was published in the American Journal of Medical Genetics Part A.
ERT used as treatment in patients with neuropathic forms of Gaucher disease
Gaucher disease is caused by mutations in the GBA1 gene that reduce activity of the enzyme glucocerebrosidase (GCase). This enzyme normally helps break down a fatty substance called glucocerebroside (Gb1), preventing its buildup in organs and tissues.
Without enough functional GCase, Gb1 accumulates, causing damage to various organs and tissues, including the liver, spleen, and bones. In some types of Gaucher disease, the brain is also affected, and patients develop neurological problems such as developmental delays and seizures.
ERT, which provides a functioning version of GCase, cannot address neurologic complications of Gaucher, but it is often used off-label in people with neuropathic forms of Gaucher to improve non-neurological symptoms. Still, there are some tissues that are difficult to reach and patients may still develop complications despite being on long-term ERT.
In this report, researchers in Italy described the case of a boy diagnosed with neuropathic Gaucher disease shortly after birth. At birth, he had an enlarged liver and spleen, along with low red blood cell and platelet counts, all of which are common signs of Gaucher disease. He also had jaundice, or yellowing of the skin and eyes, which can indicate liver dysfunction.
Due to the severity of organ involvement, he began ERT with Cerezyme (imiglucerase) at just 13 days old. While his blood counts improved with treatment, he continued to show signs of liver problems, which improved only with corticosteroid treatment, a type of medication that reduces inflammation.
By age 3, the boy showed normal weight gain and his disease appeared to be progressing slowly. Still, he experienced delayed development — he had started walking only recently and had not yet developed language skills. His liver disease had also continued to progress, and he had trouble swallowing, necessitating a feeding tube.
Boy put on corticosteroids, low-fat diet
About six months later, the boy began experiencing severe bouts of diarrhea lasting approximately 10 days per month, with as many as 30 to 40 liquid stools per day. His doctors suspected the gastrointestinal symptoms were related to Gaucher disease and increased his ERT dosage. However, the severe diarrhea persisted for four months.
Further exams revealed several enlarged lymph nodes in the abdomen, along with signs of inflammation. Stool samples also showed abnormally high levels of certain proteins, indicating PLE, a condition in which the body loses proteins through the digestive tract.
After ruling out other common causes of diarrhea, the medical team suspected the enlarged lymph nodes were causing lymphatic fluid — which is rich in proteins — to leak into the intestines, triggering PLE.
[This case highlights] “the limitations of current ERT in addressing all aspects of GD, particularly in sequestered sites like lymph nodes, and calls for new therapeutic strategies to address these challenges.
To manage his symptoms, the boy was treated with a course of corticosteroids alongside a specialized low-fat diet that included fats that are easier for the body to absorb. This approach helped resolve his diarrhea and normalize his bowel movements. After two months, both PLE and markers of inflammation had returned to normal levels.
“Notably, the clinical benefit persisted after discontinuation of steroid therapy,” the team wrote. After three months on the diet alone, the boy remained free of diarrhea episodes.
The researchers suggested several factors might have contributed to these gastrointestinal complications despite long-term ERT therapy. In particular, ERT may not effectively reach lymph nodes, especially if they have scarring or other damage.
This case highlights “the limitations of current ERT in addressing all aspects of GD, particularly in sequestered sites like lymph nodes, and calls for new therapeutic strategies to address these challenges,” they concluded.
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