Toddler’s kidney disease unmasks rare Gaucher symptom
Case report finds girl's 'unique presentation' started in kidneys
A 15-month-old girl in Egypt was diagnosed with Gaucher disease after developing severe kidney problems that failed to respond to standard therapies, according to a case report describing what researchers termed a “unique presentation” of Gaucher.
While enzyme replacement therapy (ERT) helped ease other Gaucher symptoms for the girl, it could not reverse the permanent kidney damage, underscoring the importance of early diagnosis and treatment, the researchers said.
The study, “Unexpected Gaucher disease in a case of steroid-resistant nephrotic syndrome,” was published in Pediatric Nephrology.
Gaucher disease is caused by mutations in the GBA1 gene that prevent the production of glucocerebrosidase (GCase), an enzyme that normally breaks down a fatty molecules inside cells. Without functional GCase, these fatty molecules accumulate to toxic levels, causing damage to a wide range of organs and tissues. Patients will often experience symptoms such as enlarged liver and spleen, low blood cell counts, bone problems, and sometimes neurological issues.
Though “exceptionally rare,” according to the researchers, kidney problems can also occur in people with Gaucher. Only a few cases of nephrotic syndrome — a disorder in which damage to the kidneys’ filtering units allows proteins in the blood to leak into the urine, causing swelling and low blood protein — have been reported, and these mainly appeared after a Gaucher diagnosis.
Girl’s health declines; biopsies point to metabolic storage disorder
The researchers, from Zagazig University, described the case of a 15-month-old girl with nephrotic syndrome that turned out to be an early symptom of Gaucher disease.
The girl’s medical and family history were unremarkable. Cognitive development was normal, though she showed delayed motor milestones.
Tests showed high protein loss in the urine, low albumin (the main blood protein), and signs of focal segmental glomerulosclerosis — scarring of the kidney’s filtering units that can cause progressive loss of function.
The girl did not respond to high-dose corticosteroids, the standard first-line therapy for nephrotic syndrome.
Another immunosuppressant had to be stopped due to side effects and worsening kidney function, and she improved somewhat when she switched to mycophenolate mofetil, which eased her swelling and decreased protein loss in her urine.
Still, her condition continued to worsen over several months, leading to kidney failure that required hemodialysis — a treatment in which a machine filters waste from the blood when the kidneys can no longer do so.
Six months after her initial admission, the girl experienced recurrent seizures and signs of infection, along with an enlarged liver and spleen and abnormal blood counts. Bone marrow and kidney biopsies found no cells indicative of Gaucher disease, but the findings prompted doctors to suspect a metabolic storage disorder, a group of conditions that include Gaucher.
Enzyme testing showed severely reduced GCase activity and high levels of lyso-Gb1, a biomarker of Gaucher disease. Genetic analysis also revealed a previously unreported GBA1 mutation, called c.1222A>T (p.Thr408Ser).
The girl was started on ERT every two weeks, which improved her blood counts, reduced liver and spleen size, and helped control seizures. However, the kidney damage was irreversible, leaving her dependent on long-term dialysis.
The researchers said the buildup of toxic molecules in kidney cells may directly trigger inflammation and scarring, leading to kidney injury.
“While ERT is highly effective in ameliorating [blood] and [organ] manifestations of [Gaucher disease], its ability to reverse established kidney impairment remains uncertain,” the team wrote. “This underscores the importance of early diagnosis and timely initiation of therapy to preserve kidney function and optimize outcomes. Thus, the coexistence of nephrotic syndrome, [organ enlargement], and [blood] abnormalities should prompt consideration of an underlying metabolic or genetic disorder.”
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