Man With Fabry, 57, Found to Also Have Genetic Kidney Disease

Case shows it's possible for patients to have 2 genetic kidney disorders

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
This illustration highlights the kidneys of a person taking a drink, as shown from behind.

A man living with Fabry disease for more than two decades was found to have a second co-occurring genetic condition called polycystic kidney disease, according to a recent report.

“This case demonstrates the possibility of two [genetic kidney diseases] in the same individual and the risk of one diagnosis being overlooked by the other,” the researchers wrote.

The study, “Polycystic kidney disease complicates renal pathology in a family with Fabry disease,” was published in the journal Molecular Genetics and Metabolism Reports.

Recommended Reading
kidney disease in children | Fabry Disease News | case study illustration

Fabry a Possible Cause of Kidney Disease in Children: Case Study

Researchers say misdiagnoses common in Fabry

Kidney damage is one of the most common symptoms of Fabry disease, a genetic disorder caused by mutations in the GLA gene.

In this report, a team led by scientists at the University of California, Irvine, described the case of a man who had been diagnosed with Fabry at the age of 34. Genetic testing revealed a mutation known as c.730G>A in the GLA gene, which had been previously established as disease-causing.

His Fabry symptoms included hearing loss, swelling, reduced sweating (hypohidrosis), and an eye abnormality called corneal whorling. He also experienced recurring diarrhea secondary to Fabry disease.

He was on treatment with the enzyme replacement therapy Fabrazyme (agalsidase beta).

The patient also had been diagnosed with ulcerative colitis, a form of inflammatory bowel disease, in his 40s. He was considered to be in remission, however, following treatment with an anti-inflammatory medicine called mesalamine.

At age 57, the man underwent an abdominal ultrasound, which showed a number of large cysts, or fluid-filled growths, in both of his kidneys. A few smaller cysts were found in in his liver.

While Fabry disease can sometimes cause cysts to develop in the kidneys, the ones found in this patient did not look like Fabry-related cysts, according to researchers.

“The cysts in Fabry disease are typically parapelvic [near the pelvis] and smaller than those described in our patient,” they wrote.

Notably, the man’s mother, who also had been diagnosed with Fabry disease, likewise had a history of kidney cysts.

The finding of cysts in the patient’s kidneys prompted genetic testing of several genes that are known to be associated with polycystic kidney disease (PKD). This genetic disorder is characterized by the formation of such fluid-filled growths.

Tests revealed the man had a mutation in the PKD-linked gene PKD1. This mutation, called c.11713-5C>A, was considered a variant of unknown significance, meaning its potential association with disease was unknown. Analyses of the mutation’s effect on the gene’s activity, done using computer models (in silico), were inconclusive.

“Although the in silico studies of this [mutation] have inconclusive results, the patient fills clinical criteria of [PKD], therefore, Fabry disease and polycystic kidney disease are considered two co-existing manifestations in this family,” the researchers wrote.

A literature review done by the team found one other similar case, of a 54-year-old man with Fabry and kidney cysts. However, he had no family history of Fabry. The team noted that the two kidney problems “were thought to be separate disorders in this patient, similar to our patient.”

Overall, this case highlights the need for careful investigation of the symptoms of Fabry patients, the team noted.

“Given the rarity of Fabry disease, it is common to misdiagnose the manifestations of this disease,” they wrote. “A thorough clinical evaluation and the careful review of tests of any patient with discordant findings should raise the suspicion of a second diagnosis as noted in this patient.”