Pyruvate kinase deficiency in children

Česká verze

Authors: B. Ludíková ¹; R. Mojzíková ²; P. Pospíšilová ²; J. Houda ¹; L. Sulovská ¹; M. Divoká ³; J. Hak ⁴; D. Procházková ⁵; V. Divoký ²; D. Pospíšilová ¹
Authors place of work: Dětská klinika Lékařské fakulty Univerzity Palackého a Fakultní nemocnice, Olomouc přednosta prof. MUDr. V. Mihál, CSc. ¹; Ústav biologie Lékařské fakulty Univerzity Palackého, Olomouc ředitel doc. RNDr. V. Divoký, Ph. D. ²; Hemato-onkologická klinika Lékařské fakulty Univerzity Palackého a Fakultní nemocnice, Olomouc přednosta prof. MUDr. K. Indrák, DrSc. ³; Dětská klinika Lékařské fakulty Univerzity Karlovy a Fakultní nemocnice, Hradec Králové přednosta prof. MUDr. M. Bayer, CSc. ⁴; Dětské oddělení, Krajská zdravotní, a. s. – Masarykova nemocnice, Ústí nad Labem primář MUDr. J. Škvor, CSc. ⁵
Published in the journal: Čes-slov Pediat 2012; 67 (3): 152-159.
Category: Původní práce

Summary

Purpose of the study:
Pyruvate kinase deficiency (PK) is the second most common enzymatic defect leading to hemolytic anemia. The aim is to demonstrate the clinical and laboratory findings in PK deficiency in the first pediatric patients in the Czech Republic who were defined at the molecular level.

Patients and methods:
Four children (10 months – 7 years) were examined for severe nonspherocytic hemolytic anemia with hemoglobin levels 64–97 g/l. All the children required transfusions and phototherapy after delivery, two of them even an exchange transfusion. The clinical finding was dominantly characterized by pallor, subicterus of sclerae and skin. Erythrocyte membrane disorder, hemoglobinopathies and congenital dyserythropoietic anemia were excluded using standard methods. PK activity was determined and sequencing of the gene encoding PK was done. Because of increased ferritin levels, hepcidin level was measured.

Results:
All children have macrocytic anemia with bilirubin values from 38 to 89 micromol/l. PK activity is decreased in all children (23–32%). Two patients are mixed heterozygotes for mutations c.1529C>A (p.Arg510Gln) and c.1594C>T (p.Arg532Trp) and one for the c.1493G>A (p.Arg498His) and c.1529C>A (p.Arg510Gln) mutations. In one case, a homozygous deletion in exon 11, which has not yet been described, was found. This patient with the most severe course of the disease has a high ferritin level, but a reduced level of hepcidin, which may contribute to iron overload. Coincidence with type I hemochromatosis was excluded.

Conclusion:
PK deficiency in the newborn may cause severe anemia and hyperbilirubinemia sometimes requiring an exchange transfusion and repeated administration of transfusions in infancy; their frequency is usually gradually reduced. PK deficiency may also be associated with iron overload and the need for chelation therapy. In the Czech population this disease is still underdiagnosed.

Key words:
glycolysis, pyruvate kinase, nonspherocytic hemolytic anemia, iron overload, hepcidin

Zdroje

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