A genetic screening study found a higher-than-expected prevalence of undiagnosed Fabry disease in people who had kidney failure and transplant without a known cause.
When the screening was extended to related family members, additional unidentified cases were found and treated early.
The findings led researchers to recommend genetic screening for kidney transplant patients, particularly those with an unknown cause.
The study, “Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team,” was published in the journal Biomedicines.
Progressive kidney (renal) impairment is common in people with Fabry disease and can lead to kidney failure (end-stage renal disease, or ESRD) in which a transplant is recommended.
In some cases, a transplant due to kidney failure is caused by undiagnosed Fabry disease; however, the number of people affected is unclear.
Researchers based at the University of Catania in Italy invited people who had undergone a single kidney transplant to participate in a study in which all patients underwent a genetic screening analysis for mutations (variants) in the GLA gene, which is the underlying genetic cause of Fabry disease. The study also included relatives of those who had a confirmed GLA mutation.
A total of 265 adult kidney transplant recipients were screened for Fabry disease, which included 175 males (66%) and 90 females (34%), with a mean age of 53.6 years and a mean time of 6.1 years since the transplant.
Overall, the most common cause of kidney failure (30.9%) was glomerulonephritis — inflammation of the structures in your kidneys (glomeruli) that help filter waste and fluids from the blood.
The second most prevalent cause was a genetic disorder caused by cysts in the kidney called autosomal dominant polycystic disease (21.9%). This was followed by diabetes (7.2%), and in 106 patients (40%), the cause was unknown.
Genetic screening identified seven kidney transplant recipients with GLA mutations, representing an incidence of 2.6%. This is higher than a previous review of screening studies that found a prevalence of 0.2 to 0.4% of Fabry among female transplant recipients and 0.38 to 1.12% in male patients.
“The incidence of unrecognized [Fabry disease] in our population was considerably higher than previously reported,” the researchers wrote.
Of the seven identified, a 52-year-old male had kidney transplant for kidney failure of unknown origin. He had Fabry symptoms such as abdominal pain, a rash indicating angiokeratomas, and left ventricular hypertrophy, which is the enlargement and thickening (hypertrophy) of the walls of the heart’s left ventricle.
His 20-year-old daughter with the same GLA mutation had significantly increased protein levels in the urine (proteinuria). Both the man and daughter were treated for Fabry with enzyme replacement or chaperone therapy.
A second 58-year-old woman with Fabry symptoms who received a kidney transplant also was identified post-transplant with ventricular hypertrophy and confirmed with a GLA mutation. She immediately started enzyme replacement therapy, and, at an eight-year follow-up, she had stable renal function and a slight reduction of ventricular hypertrophy.
One sister and one brother also carried the same mutation, but clinical symptoms were mild kidney problems and recurring cerebral disorders. Both were treated with enzyme replacement therapy with no progression of renal disease at eight-year follow-up.
The five remaining transplant patients were women with GLA mutations, four of which were considered disease-causing (pathogenic), but assessments did not find organ damage other than kidney disease. One individual carried a mutation that was deemed benign. None of these people required treatment.
One female patient with a GLA mutation received her kidney from her father who had the same mutation, but neither displayed further Fabry symptoms. However, she did have progressive worsening of renal function, but a biopsy performed seven years after transplant showed mild fibrosis, with no evidence of Fabry.
In total, the screening found 15 people with a GLA mutation in related family members, all of whom underwent evaluation for Fabry and received treatment as needed.
“In conclusion, this study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients,” the researchers wrote. “Although most variants were potentially pathogenic, most patients did not have clinical symptoms attributable to [Fabry disease].”
The screening identified “many patients with GLA mutations among relatives of kidney recipients, who received their treatment at a very early stage,” they added, while encouraging the “screening in all kidney transplant populations, particularly in those patients with an unknown cause of [kidney failure].”