PMID- 38415930
OWN - NLM
STAT- Publisher
LR  - 20240228
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
DP  - 2024 Feb 28
TI  - Biallelic hexokinase 1 (HK1) variants causative of non-spherocytic haemolytic 
      anaemia: A case series with emphasis on the HK1 promoter variant and literature 
      review.
LID - 10.1111/bjh.19368 [doi]
AB  - The hexokinase (HK) enzyme plays a key role in red blood cell energy production. 
      Hereditary non-spherocytic haemolytic anaemia (HNSHA) caused by HK deficiency is 
      a rare disorder with only 12 different disease-associated variants identified. 
      Here, we describe the clinical features and genotypes of four previously 
      unreported patients with hexokinase 1 (HK1)-related HNSHA, yielding two novel 
      truncating HK1 variants. The patients' phenotypes varied from mild chronic 
      haemolytic anaemia to severe infantile-onset transfusion-dependent anaemia. Three 
      of the patients had mild haemolytic disease caused by the common HK1 promoter 
      c.-193A>G variant combined with an intragenic HK1 variant, emphasizing the 
      importance of including this promoter variant in the haemolytic disease gene 
      panels. HK activity was normal in a severely affected patient with a homozygous 
      HK1 c.2599C>T, p.(His867Tyr) variant, but the affinity for ATP was reduced, 
      hampering the HK function. In cases of HNSHA, kinetic studies should be 
      considered in the functional studies of HK. We reviewed the literature of 
      previously published patients to provide better insight into this rare disease 
      and add to the understanding of genotype-phenotype correlation.
CI  - (c) 2024 The Authors. British Journal of Haematology published by British Society 
      for Haematology and John Wiley & Sons Ltd.
FAU - Ukonmaanaho, Elli-Maija
AU  - Ukonmaanaho EM
AUID- ORCID: 0000-0001-8436-3922
AD  - Division of Pediatric Hematology and Oncology, Oulu University Hospital, Oulu, 
      Finland.
AD  - University of Helsinki, Helsinki, Finland.
FAU - Dell'Anna, Silvia
AU  - Dell'Anna S
AD  - Faculty of Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Hakonen, Anna
AU  - Hakonen A
AD  - Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center, Helsinki 
      University Hospital, Helsinki, Finland.
FAU - Wartiovaara-Kautto, Ulla
AU  - Wartiovaara-Kautto U
AD  - Department of Hematology, Helsinki University Hospital, Helsinki, Finland.
FAU - Kakko, Sakari
AU  - Kakko S
AD  - Department of Hematology, Oulu University Hospital, Oulu, Finland.
FAU - Rab, Minke A E
AU  - Rab MAE
AUID- ORCID: 0000-0002-8306-8726
AD  - Central Diagnostic laboratory, University Medical Centre Utrecht, Utrecht 
      University, Utrecht, The Netherlands.
FAU - van Oirschot, Brigitte
AU  - van Oirschot B
AD  - Central Diagnostic laboratory, University Medical Centre Utrecht, Utrecht 
      University, Utrecht, The Netherlands.
FAU - Kraatari-Tiri, Minna
AU  - Kraatari-Tiri M
AD  - Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
AD  - Research Unit of Clinical Medicine and Medical Research Center Oulu, University 
      of Oulu and Oulu University Hospital, Oulu, Finland.
FAU - van Wijk, Richard
AU  - van Wijk R
AUID- ORCID: 0000-0002-8236-8292
AD  - Central Diagnostic laboratory, University Medical Centre Utrecht, Utrecht 
      University, Utrecht, The Netherlands.
FAU - Rahikkala, Elisa
AU  - Rahikkala E
AD  - Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
AD  - Research Unit of Clinical Medicine and Medical Research Center Oulu, University 
      of Oulu and Oulu University Hospital, Oulu, Finland.
LA  - eng
GR  - 338446/Research Council of Finland/
PT  - Journal Article
DEP - 20240228
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
SB  - IM
OTO - NOTNLM
OT  - HK1
OT  - anaemia
OT  - haemolysis
OT  - hexokinase deficiency
OT  - promoter variant
EDAT- 2024/02/28 12:43
MHDA- 2024/02/28 12:43
CRDT- 2024/02/28 09:52
PHST- 2024/01/21 00:00 [revised]
PHST- 2023/11/18 00:00 [received]
PHST- 2024/02/16 00:00 [accepted]
PHST- 2024/02/28 12:43 [medline]
PHST- 2024/02/28 12:43 [pubmed]
PHST- 2024/02/28 09:52 [entrez]
AID - 10.1111/bjh.19368 [doi]
PST - aheadofprint
SO  - Br J Haematol. 2024 Feb 28. doi: 10.1111/bjh.19368.