AUTHOR=Picard Véronique , Guitton Corinne , Mansour-Hendili Lamisse , Jondeau Bernard , Bendélac Laurence , Denguir Maha , Demagny Julien , Proulle Valérie , Galactéros Frédéric , Garçon Loic 

TITLE=Rapid Gardos Hereditary Xerocytosis Diagnosis in 8 Families Using Reticulocyte Indices

JOURNAL=Frontiers in Physiology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.602109

DOI=10.3389/fphys.2020.602109

ISSN=1664-042X

ABSTRACT=Gardos channelopathy (Gardos-DHS) is a constitutional haemolytic anaemia due to mutations in the KCNN4 gene. It is rarer than inherited type 1 stomatocytosis due to PIEZO1 mutations (Piezo1-DHS) and its diagnosis is particularly difficult given the absence of a specific clinical and biological phenotype.
We report here that this diagnosis can be considerably accelerated by the analysis of red blood cell (RBC) indices performed on an ADVIA 2120 (Siemens ®) analyzer, which measures reticulocyte mean corpuscular volume (rMCV) and reticulocyte mean corpuscular hemoglobin concentration (rMCHC). We studied erythrocyte and reticulocyte indices in 16 patients (9 families) with Gardos channelopathy, compared to 91 patients with Piezo1-DHS. Among Gardos-DHS cases, 12 (7 families) presented the recurrent  p.Arg352His mutation, 4 cases (2 families) presented a private KCNN4 mutation. By analyzing reticulocyte indices in Gardos-DHS, we observed that, in contrast with Piezo1-DHS,  rMCV was smaller than that of the RBCs and rMCHC was higher. We then compared the differences ΔMCV (rMCV-MCV) and ΔMCHC (rMCHC-MCHC): ΔMCV was -0.9 ± 5 vs. 19.8 ± 3 fL (p<.001) and ΔCCMH: 18.7 ±13 vs. -50±8.7 g/L (p<.001) in Gardos and Piezo1-DHS  respectively. Importantly, these observations proved to be correct for each individual subject, regardless of age, mutation  or splenectomy. Consequently, these parameters enabled to suspect Gardos channelopathy on blood count results, allowing to rapidly target these patients for genetic analysis. This is of great interest in the context of haemolysis diagnosis since it allows the patient to be referred quickly without any additional cost for a genetic study.