ESPN 50th Annual Meeting

ESPN 2017


 
COQ2 mutation, an inherited mitochondriopathy, in familial nephrotic syndrome
MILENA VOSKANYAN 1 SOFI SARINYAN 1 ARIANA GASPERT 2 CARSTEN BERGMANN 3 STEFANIE WEBER 4 MARIOS PONGAS 5 ERNST LEUMANN 6 ASHOT SARKISSIAN 1

1- “ARABKIR” MEDICAL CENTRE AND YEREVAN STATE MEDICAL UNIVERSITY, YEREVAN, ARMENIA
2- INSTITUTE OF PATHOLOGY AND MOLECULAR PATHOLOGY, UNIVERSITY HOSPITAL ZURICH
3- BIOSCIENTIA, CENTER FOR HUMAN GENETICS,INGELHEIM AND DEPARTMENT OF NEPHROLOGY, UNIVERSITY OF FREIBURG, GERMANY
4- UNIVERSITY CHILDREN’S HOSPITAL, PHILIPPS UNIVERSITY OF MARBURG, MARBURG, GERMANY
5- PAEDIATRIC NEPHROLOGY SECTOR, REGIONAL AND UNIVERSITY HOSPITAL CENTRE, NANCY, FRANCE
6- UNIVERSITY CHILDREN’S HOSPITAL, ZURICH, SWITZERLAND
 
Introduction:

The majority of steroid-resistant nephrotic syndrome (SRSN) is genetically determined. Recessive coenzyme Q2 (COQ2) mutations have recently been identified. Most affected individuals presented with neurological and muscular symptoms, whereas nephrotic syndrome (NS) has been reported very rarely. We here present siblings with SRNS. Genetic analysis performed in one of them revealed pathogenic compound heterozygous COQ2 mutations.

Material and methods:

Laboratory investigations were performed in Yerevan and Zurich, renal biopsy was evaluated in Zurich (Switzerland) and molecular genetics studied in Marburg and Ingelheim (Germany).

 

Results:

A girl aged 17 months of Armenian origin was admitted with severe NS, microhematuria and oliguria. No known consanguinity. Treatment with prednisolone for 8 weeks followed by cyclosporine A and ACE inhibitors was not effective. Two months after admission right-side hemi-myoclonus and hydrocephalus documented by MRI were diagnosed. NS persisted, renal function deteriorated (serum creatinine at the age of 2 y 3 months was 463 µmol/l) leading to death. No renal biopsy or genetic analysis could be done.

 

Two years later her younger brother aged 18 months was admitted with NS, microhematuria and oliguria. No extrarenal abnormalities. Renal biopsy revealed FSGS (NOS, not otherwise specified) and mild irregularities of the glomerular basement membrane; no abnormal mitochondria. Genetic analysis showed compound heterozygous mutations in COQ2 (maternally, COQ2 p.Leu340Val; paternally, COQ2 p.Arg173Leu). Treatment with ubiquinone (300 mg/d) introduced at CKD stage3 did not prevent progression to stage 5 at age 26 months. 

Conclusions:

Isolated SRNS due to COQ2 mutations is extremely rare. Treatment with ubiquinone (coenzyme Q10) may reverse the NS. Genetic analysis in familial cases with early renal manifestations is therefore of utmost importance. This is a good example of cooperation of different laboratories and centres in Europe.