Clinical analysis of six patients with pyruvate kinase deficiency caused by PKLR variants

Wen WANG; Yan-Xia ZHAO; Ling-Zhen WANG; Fan JIANG; Jing YANG; Li-Rong SUN; Hui-Juan XU

doi:10.7499/j.issn.1008-8830.2509155

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Chinese Journal of Contemporary Pediatrics ›› 2026, Vol. 28 ›› Issue (5) : 593-597. DOI: 10.7499/j.issn.1008-8830.2509155

CLINICAL RESEARCH

Clinical analysis of six patients with pyruvate kinase deficiency caused by PKLR variants

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Abstract

Objective To investigate the clinical features, treatment, and prognosis of pyruvate kinase deficiency (PKD) caused by PKLR gene variants. Methods Clinical data of six patients with PKD who received care at the Affiliated Hospital of Qingdao University from August 2014 to August 2025 were retrospectively analyzed. Results Of the six patients, five were children with onset in infancy, and one was an adult whose disease onset occurred at school age. All presented with jaundice and anemia, and PKD was confirmed by genetic testing. Two patients underwent splenectomy due to frequent transfusion. Three patients were mild, required no regular transfusion, and did not undergo splenectomy. One patient died. Conclusions PKD manifests chronic hemolysis with variable clinical severity. Genetic testing is recommended for diagnosis. Curative therapy remains lacking; management is mainly supportive. Splenectomy may reduce transfusion dependence and improve quality of life.

Key words

Pyruvate kinase deficiency / Clinical feature / PKLR gene variant / Splenectomy

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Wen WANG , Yan-Xia ZHAO , Ling-Zhen WANG , et al . Clinical analysis of six patients with pyruvate kinase deficiency caused by PKLR variants[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(5): 593-597 https://doi.org/10.7499/j.issn.1008-8830.2509155

References

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[1]	Grace RF, Zanella A, Neufeld EJ, et al. Erythrocyte pyruvate kinase deficiency: 2015 status report[J]. Am J Hematol, 2015, 90(9): 825-830. PMCID: PMC5053227. DOI: 10.1002/ajh.24088 . https://www.ncbi.nlm.nih.gov/pubmed/26087744 Cited in this article [5]

[2]	Nathan DG, Oski FA, Miller DR, et al. Life-span and organ sequestration of the red cells in pyruvate kinase deficiency[J]. N Engl J Med, 1968, 278(2): 73-81. DOI: 10.1056/NEJM196801112780203 . https://www.ncbi.nlm.nih.gov/pubmed/5634483 Cited in this article [1]

[3]	Mentzer WC, Baehner RL, Schmidt-Schönbein H, et al. Selective reticulocyte destruction in erythrocyte pyruvate kinase deficiency[J]. J Clin Invest, 1971, 50(3): 688-699. PMCID: PMC291977. DOI: 10.1172/JCI106539 . https://www.ncbi.nlm.nih.gov/pubmed/5101786 Cited in this article [1]

[4]

Richards

, Aziz

, Bale

, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30 .

https://www.ncbi.nlm.nih.gov/pubmed/25741868

Cited in this article [1]

[5]	Miwa S, Kanno H, Fujii H. Concise review: pyruvate kinase deficiency: historical perspective and recent progress of molecular genetics[J]. Am J Hematol, 1993, 42(1): 31-35. DOI: 10.1002/ajh.2830420108 . https://www.ncbi.nlm.nih.gov/pubmed/8416294 Cited in this article [1]

[6]	中华医学会血液学分会红细胞疾病（贫血）学组. 丙酮酸激酶缺乏症诊断与治疗专家共识（2024版）[J]. 中华医学杂志, 2024, 104(45): 4118-4124. DOI: 10.3760/cma.j.cn112137-20240430-01012 . https://www.ncbi.nlm.nih.gov/pubmed/39622742 Cited in this article [1]

[7]	Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population[J]. Blood, 2000, 95(11): 3585-3588. https://www.ncbi.nlm.nih.gov/pubmed/10828047

[8]	Secrest MH, Storm M, Carrington C, et al. Prevalence of pyruvate kinase deficiency: a systematic literature review[J]. Eur J Haematol, 2020, 105(2): 173-184. PMCID: PMC7496626. DOI: 10.1111/ejh.13424 . https://www.ncbi.nlm.nih.gov/pubmed/32279356 Cited in this article [1]

[9]

Bianchi

, Fermo

, Glader

, et al. Addressing the diagnostic gaps in pyruvate kinase deficiency: consensus recommendations on the diagnosis of pyruvate kinase deficiency[J]. Am J Hematol, 2018, 94(1): 149-161. PMCID: PMC7344868. DOI: 10.1002/ajh.25325 .

https://www.ncbi.nlm.nih.gov/pubmed/30358897

Cited in this article [1]

[10]	Canu G, De Bonis M, Minucci A, et al. Red blood cell PK deficiency: an update of PK-LR gene mutation database[J]. Blood Cells Mol Dis, 2016, 57: 100-109. DOI: 10.1016/j.bcmd.2015.12.009 . https://www.ncbi.nlm.nih.gov/pubmed/26832193 Cited in this article [1]

[11]	Grace RF, Barcellini W. Management of pyruvate kinase deficiency in children and adults[J]. Blood, 2020, 136(11): 1241-1249. DOI: 10.1182/blood.2019000945 . https://www.ncbi.nlm.nih.gov/pubmed/32702739 Cited in this article [1]

[12]	Warang P, Kedar P, Ghosh K, et al. Molecular and clinical heterogeneity in pyruvate kinase deficiency in India[J]. Blood Cells Mol Dis, 2013, 51(3): 133-137. DOI: 10.1016/j.bcmd.2013.05.006 . https://www.ncbi.nlm.nih.gov/pubmed/23770304 Cited in this article [1]

[13]	Bianchi P, Fermo E, Lezon-Geyda K, et al. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency[J]. Am J Hematol, 2020, 95(5): 472-482. PMCID: PMC8127999. DOI: 10.1002/ajh.25753 . https://www.ncbi.nlm.nih.gov/pubmed/32043619 Cited in this article [2]

[14]	Zanella A, Fermo E, Bianchi P, et al. Pyruvate kinase deficiency: the genotype-phenotype association[J]. Blood Rev, 2007, 21(4): 217-231. DOI: 10.1016/j.blre.2007.01.001 . https://www.ncbi.nlm.nih.gov/pubmed/17360088 Cited in this article [1]

[15]	Grace RF, Bianchi P, van Beers EJ, et al. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study[J]. Blood, 2018, 131(20): 2183-2192. DOI: 10.1182/blood-2017-10-810796 . https://www.ncbi.nlm.nih.gov/pubmed/29549173 Cited in this article [6]

[16]	Al-Samkari H, Shehata N, Lang-Robertson K, et al. Diagnosis and management of pyruvate kinase deficiency: international expert guidelines[J]. Lancet Haematol, 2024, 11(3): e228-e239. DOI: 10.1016/S2352-3026(23)00377-0 . https://www.ncbi.nlm.nih.gov/pubmed/38330977 Cited in this article [1]

[17]

Glenthøj

, Grace

, Lander

, et al. Comorbidities and complications in adult and paediatric patients with pyruvate kinase deficiency: analysis from the Peak Registry[J]. Br J Haematol, 2024, 205(2): 613-623. DOI: 10.1111/bjh.19601 .

https://www.ncbi.nlm.nih.gov/pubmed/39118415

Cited in this article [1]

[18]	Grace RF, Rose C, Layton DM, et al. Safety and efficacy of mitapivat in pyruvate kinase deficiency[J]. N Engl J Med, 2019, 381(10): 933-944. DOI: 10.1056/NEJMoa1902678 . https://www.ncbi.nlm.nih.gov/pubmed/31483964 Cited in this article [1]

[19]	Al-Samkari H, Galactéros F, Glenthøj A, et al. Mitapivat versus placebo for pyruvate kinase deficiency[J]. N Engl J Med, 2022, 386(15): 1432-1442. DOI: 10.1056/NEJMoa2116634 . https://www.ncbi.nlm.nih.gov/pubmed/35417638 Cited in this article [1]

[20]

Morimoto

, Kanno

, Asai

, et al. Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation[J]. Blood, 1995, 86(11): 4323-4330.

https://www.ncbi.nlm.nih.gov/pubmed/7492793

Cited in this article [1]

[21]

van Straaten

, Bierings

, Bianchi

, et al. Worldwide study of hematopoietic allogeneic stem cell transplantation in pyruvate kinase deficiency[J]. Haematologica, 2018, 103(2): e82-e86. PMCID: PMC5792292. DOI: 10.3324/haematol.2017.177857 .

https://www.ncbi.nlm.nih.gov/pubmed/29242305

Cited in this article [1]

[22]	Pang Y, Qi X, Qin J, et al. Case report: modified transplantation for pediatric patients with pyruvate kinase deficiency[J]. Front Immunol, 2024, 15: 1493398. PMCID: PMC11614771. DOI: 10.3389/fimmu.2024.1493398 . https://www.ncbi.nlm.nih.gov/pubmed/39635530 Cited in this article [1]

[23]	Shah AJ, López Lorenzo JL, Navarro S, et al. Lentiviral mediated gene therapy for pyruvate kinase deficiency: interim results of a global phase 1 study for adult and pediatric patients[J]. Blood, 2021, 138, Supplement 1: 563. DOI: 10.1182/blood-2021-148161 . Cited in this article [1]

[24]	Shah AJ, López Lorenzo JL, Grace RF, et al. RP-L301, a lentiviral-mediated gene therapy for pyruvate kinase deficiency (PKD): a phase 2 clinical trial design[J]. Blood, 2024, 144, Supplement 1: 3583.1. DOI: 10.1182/blood-2024-201734 . Cited in this article [1]