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Haematologica. 2019 Jan 17. pii: haematol.2018.205328. doi: 10.3324/haematol.2018.205328. [Epub ahead of print]

Clinical and biological features in PIEZO1-hereditary xerocytosis and Gardos-channelopathy: A retrospective series of 126 patients.

Author information

1
CHU Bicêtre, AP-HP and Université Paris Sud-Paris Saclay Pharmacie.
2
Service de Pediatrie Generale, CHU Bic&tre et filiere MCGRE, AP-HP, Le Kremlin-Bic&ecirctre, France.
3
Service de Pédiatrie, Hôpital La Timone, AP-HM, Marseille, France.
4
Service Oncologie et Hématologie, Hôpital Saint Vincent de Paul, Lille, France.
5
Laboratoire Hématologie, CHU Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
6
Laboratoire de Biochimie, CHU Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
7
Laboratoire Hématologie Biologique, CHU Saint-Eloi, Montpellier, France.
8
Genetique Medicale, Hôpital La Timone, AP-HM, Aix Marseille Univ, INSERM, Marseille, France.
9
Laboratoire Hématologie Biologique, CHU Grenoble, Grenoble, France.
10
Service de Génétique Médicale, CHU Nantes, France.
11
Service Hématologie-oncologie Pédiatrique, CHU, Saint-Etienne, France.
12
Service de Médecine Interne, CHU Saint-Etienne, France.
13
Service Hématologie, CHU Jean Minioz, Besançon, France.
14
Centre Catherine de Sienne, Nantes, France.
15
Service de Médecine interne, Hôpital La Timone, AP-HM, Marseille, France.
16
Service de Pédiatrie, CH Pau, France.
17
Centre de Reference des Syndromes Drepanocytaires Majeurs, Hopital Henri Mondor, Créteil.
18
Service de Médecine interne, CHU Henri Mondor,AP-HP, Créteil, France.
19
Service de pneumologie, CHU Bicêtre,AP-HP, Le Kremlin-Bicêtre, France.
20
Service Onco-hématologie, Hôpital Saint-Anne, Toulon, France.
21
Service de pediatrie et neonatologie, Centre Hospitalier de Bretagne Sud, Lorient, France.
22
Service de Médecine interne, CH Dax, France.
23
Génétique Médicale, CHU Amiens, France.
24
Laboratoire Hématologie, CHRU Nancy, France.
25
Laboratoire d'Hématologie, CHU Bicêtre, AP-HP, Le Kremlin-Bicêtre.
26
Service de Médecine Interne, CHU Estaing, Clermont-Ferrand, France.
27
Service Hémato-oncologie Pédiatrique, CHU Sud, Rennes, France.
28
Laboratoire Hématologie, CHU Rouen, France.
29
EA 4666 HEMATIM UPJV and Service Hématologie Biologique, CHU Amiens, France garconloic@gmail.com.

Abstract

We describe clinical, hematological and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from 6 families carried a KCNN4 mutation, 5 recurrent p.Arg352His mutations and one new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, including known recurrent mutations in only one third of the cases and private sequence variations in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation to liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families 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 indicated that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

KEYWORDS:

Iron Metabolism; Perinatal edema; Red Cell Membrane Disorders; Red Cells

PMID:
30655378
DOI:
10.3324/haematol.2018.205328
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