Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK

Juvet, Florence; Giger, Urs; Battersby, Ian; Menaut, Pierre; Syme, H M; Mooney, Carmel T.

doi:10.1186/2046-0481-66-12

Cited by 4 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PK mutations in Labrador Retrievers and Pugs seem to be limited to a few dogs and possibly a single family, whereas the other PK mutations seem to be common and even wide‐spread within a breed. In particular, PK‐deficient WHWTs and Beagles have been found throughout the United States and affected WHWTs were also identified in Europe and South America . However, it should be noted, that the frequency of the different PK mutations reported here is highly biased by the selected samples received.…”

Section: Discussionmentioning

confidence: 73%

See 1 more Smart Citation

Erythrocytic Pyruvate Kinase Mutations Causing Hemolytic Anemia, Osteosclerosis, and Secondary Hemochromatosis in Dogs

Gültekin

Raj

Foureman

et al. 2012

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. Objectives To report 3 new breed‐specific PK‐LR gene mutations and a retrospective survey of PK mutations in a small and selected group of Beagles and West Highland White Terriers (WHWT). Animals Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other), WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). Methods Exons of the PK‐LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. Results A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed‐specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK‐deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK‐deficient and 3% were carriers (0.37). Conclusions and Clinical Importance Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed‐specific mutation assays simplify the diagnosis of PK deficiency.

show abstract

Section: Discussionmentioning

confidence: 73%

“…The average age at the time of diagnosis of PK deficiency in WHWTs was 1.5 years, ranging from 2 months to 5 years of age. Most affected WHWTs were found in the United States but also in Brazil, England and Ireland; the oldest PK‐deficient WHWT died at 9 years of age.…”

Section: Resultsmentioning

confidence: 99%

Erythrocytic Pyruvate Kinase Mutations Causing Hemolytic Anemia, Osteosclerosis, and Secondary Hemochromatosis in Dogs

Gültekin

Raj

Foureman

et al. 2012

Veterinary Internal Medicne

View full text Add to dashboard Cite

show abstract

“…We acknowledge that DAT-negative IMHA can occur, 9,30,31 and that some clinical signs of hemolysis, such as icterus, may not be present early in the course of hemolysis or after initiation of immunosuppression. 32 Similarly, hemolysis can arise through nonimmune-mediated mechanisms, 21,33,34 and some signs consistent with hemolysis can be artifacts (eg, hemolyzed plasma due to traumatic venipuncture or lysis of erythrocytes in urine leading to confusion between intravascular hemolysis and hemorrhage into the urinary tract) 35 or the result of nonhemolytic disease (eg, hyperbilirubinemia due to hepatic 36 or posthepatic disease). 37 9,12,31,[41][42][43] In some cases, this likely reflects variable case and control selection between studies, but variations in test protocols and reagents are also likely a contributing factor.…”

Section: Saline Agglutination Resultsmentioning

confidence: 99%

Effect of dilution of canine blood samples on the specificity of saline agglutination tests for immune‐mediated hemolysis

Sun

Jeffery

2020

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background Saline agglutination tests (SATs) are widely recommended for diagnosis of immune‐mediated hemolytic anemia in dogs, but there are frequent false‐positive results. Objectives Specificity of SATs will improve at higher saline‐to‐blood ratios. Animals One hundred fifty dogs treated at a veterinary referral hospital with hematocrits ≤30%. Methods Prospective diagnostic accuracy study. Immune‐mediated hemolysis (IMH) was considered present if a gel direct antiglobulin test (DAT) was positive and there was clinical evidence of hemolysis (n = 9), absent if another mechanism for anemia was identified and the DAT was negative or there was no hemolysis (n = 138), and if IMH status was unclear, dogs were excluded (n = 3). Saline agglutination tests were prepared at 1 : 1, 4 : 1, 9 : 1, and 49 : 1 saline‐to‐blood ratios, and microscopic agglutination was considered a positive result. Results Specificity for IMH increased from 29% (95% confidence interval 20‐38) at a 1 : 1 dilution to 97% (93‐99) at a 49 : 1 dilution. Sensitivity was 88% (47‐100) at 1 : 1 and 4 : 1 dilutions and 67% (30‐93%) at 9 : 1 and 49 : 1 dilutions. Diagnostic accuracy increased from 33% (24–42) at 1 : 1 dilution to 95% (90‐98) at 49 : 1 dilution. Conclusions and Clinical Importance If performed using a 49 : 1 saline‐to‐blood ratio, SATs achieve high specificity for IMH. Based on a gold standard of positive DAT and evidence of hemolysis, lower saline‐to‐blood ratio results should not be used because false‐positive results are common.

show abstract

Hereditary Erythroenzymopathies

Giger¹

2022

Schalm's Veterinary Hematology

View full text Add to dashboard Cite

Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK

Cited by 4 publications

References 19 publications

Erythrocytic Pyruvate Kinase Mutations Causing Hemolytic Anemia, Osteosclerosis, and Secondary Hemochromatosis in Dogs

Erythrocytic Pyruvate Kinase Mutations Causing Hemolytic Anemia, Osteosclerosis, and Secondary Hemochromatosis in Dogs

Effect of dilution of canine blood samples on the specificity of saline agglutination tests for immune‐mediated hemolysis

Hereditary Erythroenzymopathies

Contact Info

Product

Resources

About