Unexplained kidney failure in young people

Gene: GLA

Comment on list classification: After consultation with the Genomics England clinical team it was decided to rate this gene green on the 100K panel.

Created: 27 Jun 2019, 12:02 p.m. | Last Modified: 27 Jun 2019, 12:02 p.m.

Panel Version: 1.71

GLA is associated with Fabry disease (#301500) in OMIM

PMID: 28006774 - Turkmen et al 2016 - 3 out of 313 chronic kidney disease patients not receiving renal replacement therapy (0.95%) were diagnosed of Fabry disease by GLA gene mutation analysis. The age of the patients and their family members with Fabry disease ( total number =11) was 41.3 +/- 14.5.

PMID: 15861341 - Cybulla et al 2005 - describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. The index patient was 35 years old. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet).

PMID: 15100373 - Kotanko et al 2004 - Nationwide screening of Anderson-Fabry disease among dialysis patients in Austria. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene, Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. Age at start of dialysis ranged from 27 to 53.

Created: 27 Jun 2019, 11:59 a.m. | Last Modified: 27 Jun 2019, 11:59 a.m.

Panel Version: 1.68

This gene has been reviewed by Daniel Gale on the Unexplained paediatric onset end-stage renal disease panel 2019-05-08. He states that "Fabry disease may present with renal limited disease, including presentation at end stage renal failure with no other clinical features (typically in young adults in their 20s). This has been repeatedly described in cohorts of people with kidney failure, ascertained either using biochemical or genetic screening."

Created: 27 Jun 2019, 11:58 a.m. | Last Modified: 27 Jun 2019, noon

Panel Version: 1.68