Red cell pyruvate kinase deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. PK deficiency is also the most frequent enzyme abnormality of the glycolytic pathway (Zanella et al., 2005).
Baronciani and Beutler (1994) reported successful prenatal diagnosis of PK deficiency using 2 different techniques. In the first case, they used PCR amplification and restriction endonuclease analysis and identified a mutation in fetus ... - Prenatal Diagnosis Baronciani and Beutler (1994) reported successful prenatal diagnosis of PK deficiency using 2 different techniques. In the first case, they used PCR amplification and restriction endonuclease analysis and identified a mutation in fetus genomic DNA from amniotic fluid cells. In the second case, they used cord blood to analyze 2 polymorphic sites linked to the PKRL gene and were able to identify which chromosome had been inherited from which parent.
Valentine et al. (1961) first reported pyruvate kinase deficiency in 3 patients with congenital nonspherocytic hemolytic anemia. Tanaka et al. (1962) observed a compensated hemolytic anemia in young adults who had been relatively little incapacitated. At that time, ... Valentine et al. (1961) first reported pyruvate kinase deficiency in 3 patients with congenital nonspherocytic hemolytic anemia. Tanaka et al. (1962) observed a compensated hemolytic anemia in young adults who had been relatively little incapacitated. At that time, separate alleles or even genes at different loci were thought to be the possible bases for clinical variability. Bowman and Procopio (1963) observed a severe form of hemolytic anemia in the Old Order Amish of Mifflin Co., Pennsylvania. The disorder was much more severe than that reported by Tanaka et al. (1962), leading to death in the first years of life if not treated by transfusions and splenectomy. One of the Amish patients with PK deficiency hemolytic anemia and splenectomy at age 30 months had persistent thrombocytosis and carotid artery thromboses (Ginter, 1974). Necheles et al. (1966) illustrated the clinical variability of PK deficiency in 2 unrelated patients. One had cholecystitis and cholelithiasis for which surgery was performed at age 23. He was well thereafter until age 28 when anemia developed, for which splenectomy was performed with good results. The second case was an infant who required exchange transfusion in the neonatal period because of jaundice and anemia. Results of splenectomy, performed at 14 months, were excellent. Zuelzer et al. (1968) noted marked intrafamilial clinical variability, which studies suggested was due to heterozygosity for 2 distinct interacting mutants in mildly affected relatives of severely affected probands. Persons possibly heterozygous for an anomalous pyruvate kinase had anemia in the family reported by Sachs et al. (1968). Etiemble et al. (1984) reported a family in which hemolytic anemia due to red cell PK deficiency behaved as a seemingly autosomal dominant trait. In affected members, residual PK activity was about 20% of normal, an unusually low level for heterozygotes. The anemia was mild except in the proband, a 2-year-old boy with severe anemia. Etiemble et al. (1984) suggested that the presence of one or more mutated subunits in the tetrameric form of L-type PK may lead to inactivation of these tetramers. The greater severity in the proband was considered merely part of a spectrum of expression of the same defect. Gilsanz et al. (1993) reported PK deficiency as a cause of fetal anemia and nonimmune hydrops fetalis. They described a woman in whom 3 previous pregnancies had resulted in stillbirth or early neonatal death due to anemic hydrops fetalis; PK deficiency was diagnosed in a later pregnancy by umbilical vessel sampling at 30 weeks' gestation. The infant survived with transfusion-dependent hemolytic anemia.
In 2 Japanese patients, born of consanguineous parents, with hereditary hemolytic anemia due to pyruvate kinase deficiency, Kanno et al. (1991) identified a homozygous mutation in the PKLR gene (609712.0004). Larochelle et al. (1991) identified a mutation in ... In 2 Japanese patients, born of consanguineous parents, with hereditary hemolytic anemia due to pyruvate kinase deficiency, Kanno et al. (1991) identified a homozygous mutation in the PKLR gene (609712.0004). Larochelle et al. (1991) identified a mutation in the PKLR gene (609712.0001) in French Canadian patients with pyruvate kinase deficiency. Baronciani and Beutler (1995) found 19 different mutations among 58 of 60 PKLR alleles in 30 unrelated patients with hereditary nonspherocytic hemolytic anemia due to PK deficiency. Miwa and Fujii (1996) tabulated 47 mutations in the PK gene known to result in hereditary hemolytic anemia. Rouger et al. (1996) identified 7 different PK mutations in 26 unrelated families in France; 5 of these had not previously been described. Beutler and Baronciani (1996) found that in all 55 different mutations that had been described in patients with PK-deficient hemolytic anemia, the mutations were widely distributed, occurring throughout exons 4 to 12 in this 12-exon gene. Baronciani et al. (1996) tabulated 59 different mutations in red cell pyruvate kinase of hematologic importance. In 23 patients from 21 unrelated families with PK deficiency, Fermo et al. (2005) identified a total of 27 different mutations in the PKLR gene, including 17 novel mutations. In a detailed review of PK deficiency, Zanella et al. (2005) stated that more than 150 different PKLR mutations had been identified. Pissard et al. (2006) identified 41 different mutations in the PKLR gene, including 27 novel mutations, among 56 French families with PK deficiency. Most cases were ascertained because of neonatal or chronic anemia; 2 cases were lethal in the neonatal period.
In a scheme to detect mutational events, Satoh et al. (1983) screened for activity in erythrocytes of 11 enzymes chosen because of relatively small coefficients of variation for mean activity. The object was to determine the frequency of ... In a scheme to detect mutational events, Satoh et al. (1983) screened for activity in erythrocytes of 11 enzymes chosen because of relatively small coefficients of variation for mean activity. The object was to determine the frequency of heterozygotes as identified by activities at or below 66% of the mean value. The frequency of heterozygotes per 1,000 persons varied, with PK being 13.8 per 1,000. For these same enzymes the frequency of 'rare' electrophoretic variants is 2.3/1,000 in the Japanese, almost precisely the same. Muir et al. (1984) extended the observations on PK deficiency in the Amish with identification of 8 affected persons in Geauga County, Ohio. Earlier reported cases came from Mifflin County, Pennsylvania (Bowman et al., 1965). All 8 Ohio cases were traced to a common ancestor in Mifflin County; his sister was a common ancestor of all cases identified in the original studies (Bowman et al., 1965). The common ancestor was Christopher Beiler, son of Jacob Beiler (born 1772) and Ferona Beiler and brother of Anna, wife of 'Strong' Jacob Yoder, who was the progenitor identified by Bowman et al. (1965). From laboratories performing tests for PK deficiency and from attending physicians in the province of Quebec, de Medicis et al. (1992) collected 58 cases of hereditary nonspherocytic hemolytic anemia due to deficiency of the enzyme. Using the postal addresses of the probands, a prevalence map was constructed for the various regions of the province. The prevalence was found to be higher in eastern Quebec (1 in 81,838) than in western Quebec (1 in 139,086). Fifty probands were French Canadian, whereas the remaining 6 were recent immigrants. On the basis of gene frequency, Beutler and Gelbart (2000) estimated that the prevalence of homozygous PK deficiency is 51 cases per million in the white population. Carey et al. (2000) had been centrally registering all patients with PK deficiency within the Northern Health Region of the United Kingdom since 1974. In this mainly white population, they found a prevalence of 3.3 per million, which is more than an order of magnitude lower than the prevalence predicted by Beutler and Gelbart (2000). In their registry there were very few older patients. They postulated that a possible explanation for this was that the advent of routine blood transfusion and neonatal exchange transfusion did not occur until the post-World War II period. Both Carey et al. (2000) and Beutler and Gelbart (2000) pointed out that prenatal or neonatal mortality lowers the frequency with which the disease is found in the population at large. Underdiagnosis is also likely. Beutler and Gelbart (2000) noted that in their experience misdiagnosis is common, even when PK assays are performed.