Pyruvate Kinase Deficiency malady

NIH Rare Diseases: Pyruvate kinase deficiency is a hereditary blood disorder characterized by low levels of an enzyme called pyruvate kinase, which is used by red blood cells. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia). Signs and symptoms include jaundice, enlargement of the spleen, and mild or severe hemolysis (red cell breakdown), leading to anemia. Problems may first appear in the newborn as prolonged jaundice and anemia. Older children may be pale (due to anemia) and have intermittent episodes of jaundice. Mild cases may escape detection until adulthood. Pyruvate kinase deficiency is caused by a mutation in the PKLR gene and is inherited in an autosomal recessive fashion. ³⁰

MalaCards: Pyruvate Kinase Deficiency, also known as pyruvate kinase deficiency of red cells, is related to hemolytic anemia and anemia. An important gene associated with Pyruvate Kinase Deficiency is PKLR (pyruvate kinase, liver and RBC), and among its related pathways is Glucose / Energy Metabolism. The compounds ly294002 and fructose-1,6-bisphosphate have been mentioned in the context of this disorder. Affiliated tissues include spleen and t cells, and related mouse phenotypes are hematopoietic system and normal.

Genetics Home Reference: Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Specifically, pyruvate kinase deficiency is a common cause of a type of inherited hemolytic anemia called hereditary nonspherocytic hemolytic anemia. In hereditary nonspherocytic hemolytic anemia, the red blood cells do not assume a spherical shape as they do in some other forms of hemolytic anemia.¹⁷

Wikipedia: Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency, is an inherited...⁴⁴ more...

OMIM: 266200

pyruvate kinase deficiency 7 30 16 17 33 32 pyruvate kinase deficiency of red cells 30 43 pk deficiency 30 17 pyruvate kinase deficiency of erythrocytes 30

paroxysmal kinesigenic choreoathetosis 43 deficiency of pyruvate kinase 43 pkd 17

Diseases related to pyruvate kinase deficiency by text searches and GeneDecks gene sharing:

(show top 50)    (show all 238)

id	Related Disease	Score	Top Affiliating Genes
1	hemolytic anemia	33.1	EPO, TF, HBA2, G6PD, PKLR
2	anemia	30.1	GDF15, EPO, TF, HFE, HBA2, G6PD
3	anhidrosis	29.8	PKLR, NTRK1
4	insensitivity to pain	29.8	PKLR, NTRK1
5	jaundice	29.3	PKLR, G6PD, TF
6	iron overload	29.2	GDF15, EPO, TF, HFE, HBA2
7	congenital hemolytic anemia	29.0	EPO, TF, G6PD
8	cholesterol	27.9	TF, HFE, HBA2, G6PD, PKLR, ANXA5
9	fibrosis	27.5	EPO, PRDX1, TF, HFE, ANXA5, MTHFR
10	malaria	27.5	EPO, PRDX1, TF, HFE, HBA2, G6PD
11	retinitis	26.8	EPO, TF, HFE, G6PD, NTRK1, ANXA5
12	sickle cell disease	25.1	MTHFR, ANXA5, PKLR, G6PD, HBA2, HFE
13	nephropathy	25.1	GDF15, EPO, TF, HFE, PKLR, MTHFR
14	prostatitis	25.0	GDF15, EPO, PRDX1, TF, HFE, G6PD
15	ischemia	24.6	GDF15, EPO, TF, HFE, G6PD, NTRK1
16	neuronitis	24.5	GDF15, EPO, PRDX1, TF, HFE, HBA2
17	hepatitis	24.4	GDF15, EPO, PRDX1, TF, HFE, G6PD
18	pancreatitis	24.2	GDF15, EPO, PRDX1, TF, HFE, G6PD
19	cerebritis	24.2	EPO, TF, HFE, G6PD, NTRK1, ANXA5
20	pancreatic cancer	23.9	GDF15, EPO, TF, G6PD, PKM, NTRK1
21	chronic lymphocytic leukemia	23.8	EPO, TF, HFE, ANXA5, MTHFR
22	lymphocytic leukemia	23.6	EPO, TF, HFE, G6PD, ANXA5, MTHFR
23	squamous cell carcinoma	23.3	EPO, PRDX1, G6PD, NTRK1, ANXA5, MTHFR
24	breast cancer	23.1	TF, PRDX1, EPO, GDF15, HFE, HBA2
25	carcinoma	23.0	GDF15, EPO, PRDX1, TF, HFE, HBA2
26	leukemia	21.8	GDF15, EPO, TF, HFE, HBA2, G6PD
27	congenital nonspherocytic hemolytic anemia	13.5	G6PD, PKLR
28	hereditary spherocytosis	13.2	G6PD, HFE
29	hypochromic microcytic anemia	13.1	TF, HBA2
30	fetal erythroblastosis	13.1	EPO, G6PD
31	bantu siderosis	13.0	HFE, TF
32	neonatal anemia	13.0	EPO, HBA2
33	iron metabolism disease	13.0	TF, HFE
34	hyperferritinemia-cataract syndrome	13.0	TF, HFE
35	lysinuric protein intolerance	13.0	G6PD, EPO
36	alpha thalassemia	12.9	G6PD, HBA2, HFE
37	cholelithiasis	12.9	HFE, HBA2, G6PD
38	siderosis	12.9	HFE, TF
39	essential thrombocythemia	12.8	EPO, G6PD
40	orthostatic hypotension	12.8	EPO, G6PD
41	hemochromatosis	12.8	HFE, TF
42	central retinal vein occlusion	12.8	G6PD, MTHFR
43	beta thalassemia	12.8	EPO, HBA2, G6PD
44	hydrops fetalis	12.8	G6PD, HBA2, EPO
45	cork-handlers' disease	12.7	TF, HBA2, ANXA5
46	ischemic optic neuropathy	12.7	MTHFR, G6PD
47	chronic kidney failure	12.7	TF, EPO
48	nutritional deficiency disease	12.6	TF, MTHFR
49	polycythemia vera	12.6	EPO, HFE, G6PD
50	plasmodium falciparum malaria	12.5	G6PD, TF, EPO

Clinical features from OMIM: 266200

Approved drugs:

Drug clinical trials:

Genetic tests related to pyruvate kinase deficiency:

id	Genetic test	Affiliating Genes
1	Pyruvate Kinase Deficiency clinical/research	PKLR

MalaCards organs/tissues related to pyruvate kinase deficiency:

²²

MGI Mouse Phenotypes related to pyruvate kinase deficiency:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	hematopoietic system phenotype	MP:0005397	9.1	EPO, PRDX1, NTRK1
2	normal phenotype	MP:0002873	8.0	GDF15, EPO, HFE, PKLR, NTRK1, ANXA5
3	mortality/aging	MP:0010768	6.0	EPO, G6PD, HBA2, HFE, TF, PRDX1

Articles related to pyruvate kinase deficiency:

(show all 48)

id	Title	Authors	Year	Affiliating Genes
1	Six children with pyruvate kinase deficiency from one small town: molecular characterization of the PK-LR gene. (21784452)	Christensen R.D.... Zanella A.	2011	PKLR
2	Spectrum of novel mutations in the human PKLR gene in pyruvate kinase-deficient Indian patients with heterogeneous clinical phenotypes. (18759866)	Kedar P.... Colah R.	2009	PKLR
3	Novel human pathological mutations. Gene symbol: PKLR. Disease: pyruvate kinase deficiency. (19309805)	Manco L.... Ribeiro M.L.	2009	PKLR
4	Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. (19120353)	Finkenstedt A.... Zoller H.	2009	GDF15
5	Rescue of pyruvate kinase deficiency in mice by gene therapy using the human isoenzyme. (19755962)	Meza N.W.... Segovia J.C.	2009	PKLR
6	Novel human pathological mutations. Gene symbol: PKLR. Disease: pyruvate kinase deficiency. (19320017)	Manco L.... Ribeiro M.L.	2009	PKLR
7	Novel human pathological mutations. Gene symbol: PKLR. Disease: pyruvate kinase deficiency. (19309787)	Manco L.... Ribeiro M.L.	2009	PKLR
8	Adenosine triphosphate depletion of erythrocytes simu lates the phenotype associated with pyruvate kinase deficiency and confers prot ection against Plasmodium falciparum in vitro. (19743919)	Ayi K.... Kain K.C.	2009	PKLR
9	Relative red blood cell enzyme levels as a clue to the diagnosis of pyruvate kinase deficiency. (18726918)	Titapiwatanakun R.... Arndt C.A.	2008	PKLR
10	Pyruvate kinase deficiency and malaria. (18420493)	Ayi K.... Kain K.C.	2008	PKLR
11	Prevalence of pyruvate kinase deficiency among the south Iranian population: quantitative assay and molecular analysis. (17977029)	Yavarian M.... Afrasiabi A.R.	2008	PKLR
12	Gene symbol: PKLR. Disease: Pyruvate kinase deficiency. (18846674)	Manco L.... Ribeiro M.L.	2008	PKLR
13	Pyruvate kinase deficiency protects against malaria in humans. (18460648)	Durand P.M.... Coetzer T.L.	2008	PKLR
14	Pyruvate kinase deficiency in a South African kindred caused by a 1529A mutation in the PK-LR gene. (18683378)	Durand P.M.... Coetzer T.L.	2008	PKLR
15	Molecular characterisation of pyruvate kinase deficiency--concerns about the description of mutant PKLR alleles. (17222205)	van Wijk R.... van Solinge W.W.	2007	PKLR
16	Glycolytic inhibition by mutation of pyruvate kinase gene increases oxidative stress and causes apoptosis of a pyruvate kinase deficient cell line. (17662887)	Aisaki K.... Kanno H.	2007	ANXA5, PRDX1
17	First-trimester prenatal diagnosis of pyruvate kinase deficiency in an Indian family with the pyruvate kinase-Amish mutation. (17952871)	Kedar P.S.... Colah R.B.	2007	PKLR
18	Moya moya syndrome in a child with pyruvate kinase deficiency and combined prothrombotic factors. (17621533)	Skardoutsou A.... Koukoutsakis P.	2007	MTHFR
19	Transgenic rescue of hemolytic anemia due to red blood cell pyruvate kinase deficiency. (17550844)	Kanno H.... Fujii H.	2007	PKLR
20	Pyruvate kinase deficiency: the genotype-phenotype association. (17360088)	Zanella A.... Valentini G.	2007	PKLR
21	Pyruvate kinase deficient hemolytic anemia in the Northern Irish population. (17574881)	Percy M.J.... McMullin M.F.	2007	PKLR
22	Hereditary enzyme defects of erythrocytes: glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency (16450734)	Sedano I.I.... Huber A.R.	2006	G6PD
23	Red cell pyruvate kinase deficiency in neonatal jaundice cases in India. (17127778)	Kedar P.S.... Mohanty D.	2006	G6PD
24	PK Aarau: first homozygous nonsense mutation causing pyruvate kinase deficiency. (15491302)	Sedano I.B.... Huber A.	2004	PKLR
25	Ex vivo analysis of aberrant splicing induced by two donor site mutations in PKLR of a patient with severe pyruvate kinase deficiency. (15059150)	Wijk R.... van Solinge W.W.	2004	PKLR
26	Disruption of a novel regulatory element in the erythroid-specific promoter of the human PKLR gene causes severe pyruvate kinase deficiency. (12393511)	van Wijk R.... Nielsen F.C.	2003	PKLR
27	Consequences at mRNA level of the PKLR gene splicing mutations IVS10(+1)G-->C and IVS8(+2)T-->G causing pyruvate kinase deficiency. (12181074)	Manco L.... Tamagnini G.	2002	PKLR
28	From gene to disease; hereditary non-spherocytic hemolytic anemia caused by pyruvate kinase deficiency (12382367)	de Vooght K.M.... van Solinge W.W.	2002	PKLR
29	Iron status and HFE genotype in erythrocyte pyruvate kinase deficiency: study of Italian cases. (11482880)	Zanella A.... Sampietro M.	2001	HFE
30	Congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency. (11668614)	Indo Y.... Matsuda I.	2001	NTRK1, PKLR
31	Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients. (11328279)	Zanella A.... Cotton F.	2001	PKLR
32	Eight novel mutations and consequences on mRNA and protein level in pyruvate kinase-deficient patients with nonspherocytic hemolytic anemia. (10679942)	Kugler W.... Lakomek M.	2000	PKLR
33	A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency. (11054094)	Manco L.... Tamagnini G.	2000	PKLR
34	A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha-2 globin gene variant (Hb Conakry). (9886305)	Cohen-Solal M.... Galacteros F.	1998	PKLR, HBA2
35	Novel mutations and structural implications in R-type pyruvate kinase-deficient patients from Southern Italy. (9482576)	Pastore L.... Salvatore F.	1998	PKLR
36	Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. (9827908)	Zarza R.... Vives Corrons J.L.	1998	PKLR
37	Molecular characterization of PK-LR gene in pyruvate kinase-deficient Italian patients. (9160692)	Zanella A.... Sirchia G.	1997	PKLR
38	Molecular analysis of 29 pyruvate kinase-deficient patients from central Europe with hereditary hemolytic anemia. (9057665)	Lenzner C.... Thiele B.J.	1997	PKLR
39	Muscle pyruvate kinase deficiency: glycogen storage disease or mitochondrial myopathy? (9127121)	Poulton K.R.... Rossi M.L.	1997	PKM
40	Molecular study of pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia. (7706479)	Baronciani L.... Beutler E.	1995	PKLR
41	Mutations in the R-type pyruvate kinase gene and altered enzyme kinetic properties in patients with hemolytic anemia due to pyruvate kinase deficiency. (7948315)	Lakomek M.... Schroter W.	1994	PKLR
42	Erythropoietin in the treatment of iron overload in a patient with hemolytic anemia and pyruvate kinase deficiency. (7976118)	Vukelja S.J.	1994	EPO
43	Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. (8161798)	Kanno H.... Bowman H.S.	1994	PKLR
44	Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. (8483951)	Baronciani L.... Beutler E.	1993	PKLR
45	Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency. (2018831)	Neubauer B.... Schroter W.	1991	PKLR
46	Heterozygous pyruvate kinase deficiency and severe hemolytic anemia in a pregnant woman with concomitant, glucose-6-phosphate dehydrogenase deficiency. (2049468)	Vives Corrons J.L.... Linares M.	1991	G6PD
47	Diagnosis of pyruvate kinase deficiency in a transfusion-dependent patient with severe hemolytic anemia. (2220762)	Rijksen G.... Staal G.E.	1990	PKM
48	Iron overload in congenital hemolytic anemia caused by pyruvate kinase deficiency. A major late complication (2141411)	Boivin P.... Galand C.	1990	TF

Genes related to pyruvate kinase deficiency according to GeneCards:

(show all 12)

id	Symbol	Description	Score	GeneCards Section Context
1	PKLR	pyruvate kinase, liver and RBC	11.0	Publications
2	G6PD	glucose-6-phosphate dehydrogenase	11.0	Publications
3	GDF15	growth differentiation factor 15	11.0	Publications
4	PRDX1	peroxiredoxin 1	11.0	Publications
5	HBA2	hemoglobin, alpha 2	11.0	Publications
6	PKM	pyruvate kinase, muscle	11.0	Disorders, Publications
7	NTRK1	neurotrophic tyrosine kinase, receptor, type 1	11.0	Publications
8	HFE	hemochromatosis	11.0	Publications
9	ANXA5	annexin A5	11.0	Publications
10	TF	transferrin	11.0	Publications
11	MTHFR	methylenetetrahydrofolate reductase (NAD(P)H)	11.0	Publications
12	EPO	erythropoietin	11.0	Publications

Pathways related to pyruvate kinase deficiency according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Glucose / Energy Metabolism3	9.5	PKM, G6PD, PRDX1

Compounds related to pyruvate kinase deficiency according to GeneDecks:

(show all 50)

id	Compound	Score	Top Affiliating Genes
1	ly29400232	10.3	ANXA5
2	fructose-1,6-bisphosphate32	10.1	G6PD, PKM
3	aspartate32	10.0	NTRK1, HFE
4	cellulose acetate32	9.9	G6PD, PKM, HBA2
5	fumarate32 9 9	11.8	EPO, G6PD
6	glucose32	9.8	PKM, PRDX1
7	23-diphosphoglycerate32	9.8	G6PD, EPO, HBA2
8	dehydroascorbic acid32	9.8	TF, G6PD
9	recormon32	9.8	TF, EPO
10	ferric gluconate32	9.8	TF, EPO
11	iron sucrose32	9.7	TF, EPO
12	deferiprone32	9.7	EPO, TF
13	aluminium32 9 9	11.7	EPO, TF
14	iron dextran32 9 9	11.7	EPO, TF
15	nandrolone decanoate32 9 9	11.7	TF, EPO
16	succinylacetone32	9.6	EPO, TF
17	fenton32	9.6	EPO, TF
18	zinc protoporphyrin32	9.5	EPO, TF, G6PD
19	ethidium bromide32	9.5	G6PD, ANXA5, TF
20	chi 232	9.4	HFE, MTHFR
21	ribavirin32 34 9 9	12.4	TF, EPO, G6PD
22	cytarabine32 34 9 9	12.3	EPO, NTRK1, ANXA5
23	uric acid32 18	10.3	G6PD, MTHFR, HFE
24	carbohydrates32	9.2	ANXA5, TF, PKLR
25	protoporphyrin ix32 9 18 9	12.2	TF, EPO
26	pyruvate32	9.2	PRDX1, HFE, G6PD, PKLR, PKM
27	azathioprine32 34 9 9	12.2	EPO, G6PD, MTHFR
28	mitomycin c32	9.1	ANXA5, TF, EPO
29	alpha tocopherol32	9.1	MTHFR, TF, G6PD
30	butyrate32	9.0	HBA2, NTRK1, EPO, ANXA5
31	triamcinolone acetonide32	9.0	TF, EPO
32	imatinib32 34 9 9	12.0	ANXA5, NTRK1, EPO
33	oxygen32 18	10.0	NTRK1, PKM, G6PD, HBA2, ANXA5
34	betacarotene32	8.9	MTHFR, ANXA5, TF
35	choline32 9 18 9	11.8	TF, NTRK1, MTHFR
36	atp32	8.7	ANXA5, NTRK1, PKLR, HBA2, G6PD, PKM
37	vitamin b1232	8.7	MTHFR, TF, EPO, G6PD
38	iron32 18	9.6	HBA2, HFE, TF, EPO, GDF15
39	folate32	8.6	MTHFR, G6PD, EPO, TF
40	cisplatin32 34 9 9	11.5	EPO, G6PD, MTHFR, ANXA5
41	testosterone32 9 18 9	11.3	HFE, G6PD, EPO, MTHFR, NTRK1
42	thymidine32 18	9.3	ANXA5, MTHFR, EPO, HBA2
43	cyclosporin a32 42	9.3	ANXA5, TF, MTHFR, EPO
44	lactate32	8.2	PKM, G6PD, TF, NTRK1, ANXA5, EPO
45	serine32	8.1	NTRK1, PRDX1, PKLR, GDF15, MTHFR, G6PD
46	estrogen32	8.0	HFE, MTHFR, TF, NTRK1, GDF15, G6PD
47	tyrosine32	8.0	EPO, NTRK1, ANXA5, PKLR, PKM, HFE
48	creatinine32	7.9	MTHFR, EPO, PRDX1, TF, G6PD, NTRK1
49	alanine32	7.9	PKM, MTHFR, HBA2, HFE, TF, NTRK1
50	ascorbic acid32 18	8.7	EPO, TF, HFE, G6PD, ANXA5, MTHFR

Cellular components related to pyruvate kinase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	basal part of cell	GO:045178	9.4	HFE, TF

Biological processes related to pyruvate kinase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	hydrogen peroxide catabolic process	GO:042744	9.8	HBA2, PRDX1
2	erythrocyte maturation	GO:043249	9.6	G6PD, EPO
3	positive regulation of Ras protein signal transduction	GO:046579	9.2	NTRK1, EPO

Molecular functions related to pyruvate kinase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	pyruvate kinase activity	GO:004743	9.8	PKLR, PKM
2	potassium ion binding	GO:030955	9.7	PKLR, PKM
3	peroxidase activity	GO:004601	9.5	HBA2, PRDX1
4	eukaryotic cell surface binding	GO:043499	9.4	ANXA5, EPO