Case study 2: Genetic diagnosis allows targeted therapies.

At the age of 6, a male patient was diagnosed with steroid-resistant nephrotic syndrome (SRNS)—a disease that causes abnormalities in kidney function and excess of protein in the urine (proteinuria), which often leads to kidney failure. Researchers in EURenOmics discovered that his symptoms are caused by variants in the gene ADCK4, which impair the biosynthesis of Coenzyme Q10 (CoQ10) and lead to a kidney-specific mitochondrial dysfunction. Supplementation with oral CoQ10 reduces proteinuria. The same variant was found in the patient’s sister, who also had proteinuria, but showed no symptoms. CoQ10 supplementation has been applied in both children to maintain the kidney function in long-term.

To facilitate genetic diagnosis, the researchers have developed NGS gene panels that allow doctors to quickly check whether a sick child has variants in genes known to be associated with certain kidney diseases. The screening of a cohort of 1000 children with SRNS revealed that up to 10% of the patients who receive a genetic diagnosis are affected by treatable hereditary defects of CoQ10 biosynthesis. Hence, a progressive kidney disease previously considered untreatable has turned into an easily treatable condition in at least some of the affected children, thanks to progress in gene discovery and routine genetic diagnostics [26].

The precise genetic diagnosis allowed for genetic counseling important for future family planning. The parents were recommended in-vitro fertilization with preimplantation diagnostics, which allowed them to get a healthy son.