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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1554-1564
Red Cell & its Disorders
Clinical and biological features in PIEZO1- hereditary xerocytosis and Gardos chan- nelopathy: a retrospective series of 126 patients
Véronique Picard,1,2 Corinne Guitton,3 Isabelle Thuret,4 Christian Rose,5 Laurence Bendelac,1 Kaldoun Ghazal,6 Patricia Aguilar-Martinez,7 Catherine Badens,8 Claire Barro,9 Claire Bénéteau,10 Claire Berger,11 Pascal Cathébras,12 Eric Deconinck,13 Jacques Delaunay,14 Jean-Marc Durand,15 Nadia Firah,16 Frédéric Galactéros,17 Bertrand Godeau,18 Xavier Jaïs,19 Jean-Pierre de Jaureguiberry,20 Camille Le Stradic,21 François Lifermann,22 Robert Maffre,1 Gilles Morin,23 Julien Perrin,24 Valérie Proulle,1 Marc Ruivard,25 Fabienne Toutain,26 Agnès Lahary27 and Loïc Garçon1,28
1Laboratoire d'Hématologie, Center Hospitalier Universitaire (CHU) Bicêtre, Assistance publique – Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre; 2Université Paris Sud Paris Saclay, Faculté de Pharmacie, Chatenay Malabry; 3Service de Pédiatrie Générale, CHU Bicêtre et Filière MCGRE, AP-HP, Le Kremlin-Bicêtre; 4Service de Pédiatrie, Hôpital La Timone, Aix Marseille University, Marseille; 5Service d’Oncologie et d’Hématologie, Hôpital Saint Vincent de Paul, Lille; 6Laboratoire de Biochimie, CHU Bicêtre, AP-HP, Le Kremlin- Bicêtre; 7Laboratoire d’Hématologie Biologique, CHU Saint-Eloi, Montpellier; 8Service de Génétique Médicale, Hôpital La Timone, Marseille; 9Laboratoire d’Hématologie Biologique, CHU Grenoble, Grenoble; 10Génétique Médicale, CHU Nantes, Nantes; 11Service d’Hématologie-Oncologie Pédiatrique, CHU, Saint-Etienne; 12Service de Médecine Interne, CHU Saint-Etienne; 13Service d’Hématologie, CHU Jean Minioz, Besançon; 14Centre Catherine de Sienne, Nantes; 15Service de Médecine Interne, Hôpital La Timone, Marseille; 16Service de Pédiatrie, Centre Hospitaliere (CH) Pau; 17Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor, AP-HP, Créteil; 18Service de Médecine Interne, CHU Henri Mondor, AP-HP, Créteil; 19Service de Pneumologie, CHU Bicêtre, AP-HP, Le Kremlin-Bicêtre; 20Service de Médecine Interne, Sainte Anne, Toulon; 21Service de Pédiatrie –Néonatologie, CH de Bretagne Sud, Lorient; 22Service de Médecine interne, CH Dax; 23Génétique Médicale, CHU Amiens; 24Laboratoire d'Hématologie, CHRU Nancy; 25Service de Médecine Interne, CHU Estaing, Clermont-Ferrand; 26Service d’Hémato-Oncologie Pédiatrique, CHU Sud, Rennes; 27 Laboratoire d'Hématologie, CHU Rouen and 28Equipe d’Accueil 4666 HEMATIM Université de Picardie Jules Verne and Service d’Hématologie Biologique, CHU Amiens, France
ABSTRACT
We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with heredi- tary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families car- ried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two domi- nant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-heredi- tary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of fam- ilies and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a ‘Gardos channelopathy’. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopa- thy are not the same disease although they share hemolysis, a high rate of
Correspondence:
LOÏC GARÇON
Garcon.Loic@chu-amiens.fr
Received: September 4, 2018. Accepted: January 15, 2019. Pre-published: January 24, 2019.
doi:10.3324/haematol.2018.205328
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