Fabry a Possible Cause of Kidney Disease in Children: Case Study
A rare case of end-stage kidney disease was discovered in a young boy with Fabry disease, a case study reported.
In such cases of unexplained kidney failure in children, a detailed family history should be taken, and Fabry considered a possible cause, the researchers recommended.
The case study, “Early renal failure in childhood in a male with Fabry disease,” was published in the journal BMJ Case Reports.
Fabry disease is a disorder caused by the reduced activity or absence of the alpha-galactosidase A (Gal A) enzyme. Gal A is responsible for breaking down fat-like molecules, mainly globotriaosylceramide (Gb3 or Gl-3), in cellular recycling compartments called lysosomes.
A lack of Gal A leads to the toxic buildup of these fatty molecules in most body tissues, including small blood vessels, and results in organ damage. Very low or absent Gal A activity is associated with the classic type of Fabry; some residual enzyme activity causes the late-onset form.
Kidney failure due to chronic kidney disease is a late complication, mainly occurring about the fifth decade of life, among those with classical Fabry. It is very rarely seen in children.
In this report, researchers at University College London, in the U.K., describe the case of an 11-year-old boy who developed kidney failure due to undiagnosed Fabry. The boy ultimately required dialysis and a transplant.
Upon examination, he had many signs and symptoms of Fabry, including episodes of severe pain and burning, decreased sweating, digestive tract symptoms, and eye deposits. The child also had clusters of small reddish or dark-blue spots on the skin, called angiokeratomas. Blood tests revealed high urea and creatinine levels, both indicators of chronic kidney disease.
Based on these findings, the boy was started on kidney dialysis while tests were performed to determine the cause of his kidney failure. A kidney biopsy showed deposits in the lysosomes. He had low levels of Gal A in his bloodstream and immune cells and an unusual mutation in the GLA gene that encodes for the Gal A enzyme.
Accordingly, he was diagnosed with Fabry at the age of 12. Medical history indicated growth deficiency and anemia, or low levels of red blood cells, that required iron supplement at age 10.
Because of his Fabry diagnosis, he was started on Fabrazyme (agalsidase beta), an approved enzyme replacement therapy (ERT) that provided an external source of the Gal A enzyme. After one year of ERT, general improvement and normal heart tests were reported. However, the boy’s kidney disease persisted.
At 16, he moved to another European country and switched to Replagal (agalsidase alfa), another version of the Gal A enzyme, for unknown reasons. Replagal is not unavailable in the U.S.
However, the patient experienced difficulties with dialysis, and, at age 18, he received a kidney transplant from a deceased donor. That procedure was successful.
When the patient was 24, he moved to the U.K., but traveled back to the previous country for ERT infusion. Due to COVID-19 pandemic restrictions, he missed some ERT. Before re-starting the enzyme-replacement therapy, he was admitted to the emergency department after four weeks of loose stool, abdominal pain, and one week of vomiting.
CT scans of his abdomen showed new inflammatory bowel disease (IBD), later diagnosed as mild active chronic proctocolitis, or inflammation of the rectal lining. Because there were no signs of infection or problems with medication, it was considered related to Fabry.
Intravenous (into-the-vein) treatment with the steroid hydrocortisone did not improve his symptoms or reduce inflammation. His symptoms did improve after switching to oral prednisolone, another steroid, and infliximab, a biologic anti-inflammatory therapy.
During his hospital stay, he was switched from mycophenolate, an immune suppressant to protect against transplant rejection, to azathioprine, which also helped his IBD.
Although he had relatives also affected by Fabry, they lived in another country, and details were unavailable. There also was no family history of genetic disorders or delays in development.
Now 27, the patient lives in the U.K. and continues to experience occasional tingling and burning symptoms, reduced sweating, and fatigue. He also still has a few eye problems and angiokeratomas. Recent tests showed an enlarged heart, mild high blood pressure in the lungs’ arteries, normal overall blood pressure, and sleeping difficulties.
“End-stage renal disease due to Fabry disease is very rare, but possible in childhood,” the researchers wrote. “A detailed family history should be taken, and Fabry disease should be included in the differential diagnosis as a possible cause of unexplained renal failure in young males.”