ESPN 53rd Annual Meeting

ESPN 2021


 
Systematic evaluation of olfaction in patients with hereditary cystic kidney diseases/renal ciliopathies
MAREIKE DAHMER-HEATH 1 VALENTIN SCHRIEVER 2 SABINE KOLLMANN 1 CAROLIN SCHLEITHOFF 1 ANDREA TITIENI 1 METIN CETINER 3 LUDWIG PATZER 4 BURKHARD TÖNSHOFF 5 MATTHIAS HANSEN 6 PETRA PENNEKAMP 1 JOACHIM GERß 7 MARTIN KONRAD 1 JENS KÖNIG 1

1- UNIVERSITY CHILDRENS HOSPITAL, DEPARTMENT OF GENERAL PEDIATRICS, UNIVERSITäTSKLINIKUM MÜNSTER, MÜNSTER, GERMANY
2- ABTEILUNG FÜR NEUROPäDIATRIE, MEDIZINISCHE FAKULTäT CARL GUSTAV CARUS, DRESDEN, GERMANY
3- DEPARTMENT OF PEDIATRIC NEPHROLOGY, PEDIATRICS II, UNIVERSITY OF DUISBURG-ESSEN, ESSEN, GERMANY
4- CHILDRENS HOSPITAL ST. ELISABETH AND ST. BARBARA, HALLE (SAALE), GERMANY
5- DEPARTMENT OF PEDIATRICS I, UNIVERSITY CHILDRENS HOSPITAL HEIDELBERG, HEIDELBERG, GERMANY
6- CLEMENTINE KINDERHOSPITAL, FRANKFURT AM MAIN, GERMANY
7- INSTITUTE OF BIOSTATISTICS AND CLINICAL RESEARCH, UNIVERSITY OF MÜNSTER, MÜNSTER, GERMANY
 
Introduction:

One of the perceptions cilia are involved in is the sense of smell. Motile cilia are equipped with odorant receptors and play a critical role in odor transmittance and detection. As a consequence, genetic defects disrupting the functional or structural integrity of these cilia may cause olfactory dysfunction. One of the ciliopathies that has already been associated with hyposmia is Bardet-Biedl syndrome (BBS). BBS is a multivisceral syndromic disorder caused by genetic defects located at the ciliary base. However, reports of olfactory dysfunction in other hereditary kidney diseases that are also caused by mutations in genes located at the cilium (nephronophthisis, polycystic kidney diseases) are sparse. Here we provide a systematic survey on olfaction in a large cohort of children, adolescents and adults displaying genetically determined ciliopathies.

Material and methods:

We performed a match- controlled systematic olfactory evaluation in a group of 75 patients with a defined genetic background using age adapted and validated odour identification tests.

Results:

Identification tests revealed a significant olfactory deficit in patients carrying TMEM67 variants (n=4), while all other genetic disorders causing nephronophthisis (n=25) or polycystic kidney disease (n=18) were not associated with an impaired sense of smell. In patients suffering from BBS, olfactory performance was depending on the underlying molecular defect. While defects in the BBS1 gene (n=9) had no impact on the sense of smell, all other BBS gene disorders (n=19) were associated with significant hyposmia. Noteworthy, there was no correlation of the olfactory deficit with the level of renal impairment.

Conclusions:

Hyposmia is a critical clinical feature of most but not all (except for BBS1) genetically determined BBS patients. Furthermore, COACH syndrome caused by mutations in the TMEM67 gene was found to display significant olfactory impairment, a feature that has not been reported as part of the clinical spectrum so far.