Prevalence of pyruvate kinase deficiency in a northern European population in the north of England

Carey, Peter; Chandler, John; Hendrick, Alex; Reid, M M; Saunders, Peter; Tinegate, Hazel; Taylor, Pennie; West, Nicholas P.

doi:10.1182/blood.v96.12.4005.h8004000e_4005_4006

Cited by 18 publications

(9 citation statements)

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“…Some authors have estimated a prevalence of 1∶20 000 in the general white population [23] . In Europe, an incidence of 3.3 per million has been reported in the north of England [24] , and a prevalence of 0.24% and 1.1% have been described in Spain [25] and Turkey [26] , respectively. In Asia, the frequency of PK deficiency among the Hong Kong Chinese population was <0.1% [27] whilst among the south Iranian population was 1.9% [28] .…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria

et al. 2012

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BackgroundPyruvate kinase (PK) deficiency, causing hemolytic anemia, has been associated to malaria protection and its prevalence in sub-Saharan Africa is not known so far. This work shows the results of a study undertaken to determine PK deficiency occurrence in some sub-Saharan African countries, as well as finding a prevalent PK variant underlying this deficiency.Materials and MethodsBlood samples of individuals from four malaria endemic countries (Mozambique, Angola, Equatorial Guinea and Sao Tome and Principe) were analyzed in order to determine PK deficiency occurrence and detect any possible high frequent PK variant mutation. The association between this mutation and malaria was ascertained through association studies involving sample groups from individuals showing different malaria infection and outcome status.ResultsThe percentage of individuals showing a reduced PK activity in Maputo was 4.1% and the missense mutation G829A (Glu277Lys) in the PKLR gene (only identified in three individuals worldwide to date) was identified in a high frequency. Heterozygous carrier frequency was between 6.7% and 2.6%. A significant association was not detected between either PK reduced activity or allele 829A frequency and malaria infection and outcome, although the variant was more frequent among individuals with uncomplicated malaria.ConclusionsThis was the first study on the occurrence of PK deficiency in several areas of Africa. A common PKLR mutation G829A (Glu277Lys) was identified. A global geographical co-distribution between malaria and high frequency of PK deficiency seems to occur suggesting that malaria may be a selective force raising the frequency of this 277Lys variant.

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Section: Discussionmentioning

confidence: 99%

Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria

et al. 2012

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“…Epidemiology PKD exhibits autosomal recessive inheritance in nearly all cases and is widely distributed geographically. The frequency is not precisely defined, with a wide estimated prevalence of 3:1 000 000 to 1:20 000 (Beutler & Gelbart, 2000;Carey et al, 2000). Reported heterozygote frequencies among different populations based on qualitative and quantitative biochemical analysis range from 0Á15% to 6%.…”

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confidence: 99%

How we manage patients with pyruvate kinase deficiency

2019

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Summary Novel therapies in development have brought a new focus on pyruvate kinase deficiency (PKD), the most common congenital haemolytic anaemia due to a glycolytic enzyme deficiency. With an improved recognition of its clinical presentation and understanding of the diagnostic pathway, more patients are likely to be identified with this anaemia. Complications, including gallstones and non‐transfusion‐related iron overload, require monitoring for early diagnosis and management. Current management remains supportive with red cell transfusions, chelation and splenectomy. Decisions to transfuse and/or splenectomise must be individualised. Haematopoietic stem cell transplant has been pursued in a small number of patients with mixed outcomes. Novel treatment approaches, which range from a small molecule pyruvate kinase activator to gene therapy, may transform the way in which PKD is managed in the future. In this review, we discuss the pathophysiology of PKD and present our approaches to diagnosis, monitoring and management of patients with this anaemia.

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“…The diagnosed prevalence of PK deficiency in the general population is estimated to be between 3.2 and 8.5 cases per million individuals 6‐10 . Higher prevalence is observed in specific populations, such as in the US Amish community, due to the founder effect 11,12 …”

Section: Introductionmentioning

confidence: 99%

Comorbidities and complications in adults with pyruvate kinase deficiency

Boscoe

Yan

Hedgeman

et al. 2021

European J of Haematology

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Objectives Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified. Methods Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age‐ and sex‐matched cohort from a general insured US population without PK deficiency. Results Compared with the matched population (n = 1220), patients with PK deficiency (n = 122) had significantly higher lifetime rates of osteoporosis, liver cirrhosis, and pulmonary hypertension; splenectomy and cholecystectomy rates were also significantly higher in the 8 years before the index date. Sixty‐five (53.3%) patients with PK deficiency were classified as regularly transfused, 30 (24.6%) as occasionally transfused, and 27 (22.1%) as never transfused. Regularly transfused patients were significantly more likely than never transfused patients to have had splenectomy, cholecystectomy, and/or thrombosis. Liver iron overload was reported in 62% of patients and occurred regardless of transfusion cohort. Conclusions Even never transfused patients with PK deficiency had higher rates of select comorbidities and complications than individuals without PK deficiency.

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Prevalence of pyruvate kinase deficiency in a northern European population in the north of England

Cited by 18 publications

References 1 publication

Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria

Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria

How we manage patients with pyruvate kinase deficiency

Comorbidities and complications in adults with pyruvate kinase deficiency

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