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Pyruvate kinase deficiency and leg ulcers
Insights
A novel pyruvate kinase (PK) variant causes hemolytic anemia and leg ulcers in a family. This PK deficiency variant shows altered enzyme kinetics and reduced stability, potentially impacting red blood cell properties.
Area of Science:
- Biochemistry
- Hematology
- Genetics
Background:
- Pyruvate kinase (PK) deficiency is a genetic disorder causing hemolytic anemia.
- Leg ulcers are a known, though less common, complication of PK deficiency.
Observation:
- A family presented with a new PK variant, with four of five affected homozygous members exhibiting leg ulcers.
- The propositus, an 18-year-old male, experienced recurrent hemolytic anemia crises and leg ulcers.
- A splenectomy and skin graft were unsuccessful in treating the leg ulcer.
Findings:
- Dialyzed hemolysates revealed a kinetically abnormal PK enzyme, resistant to fructose diphosphate activation.
- The enzyme exhibited moderately decreased thermostability with normal electrophoretic mobility.
- This specific PK variant appears linked to the manifestation of leg ulcers.
Implications:
- The findings suggest a correlation between specific PK variants and the development of leg ulcers in PK deficiency.
- Altered PK enzyme kinetics may affect red blood cell rheology in vivo, contributing to ulcer formation.
- Further research into PK variants and their rheologic effects could inform treatment strategies for associated complications.
Abstract:
We report a family with a new pyruvate kinase (PK) variant in which leg ulcers have been present in four of the five affected homozygous family members, but not in any of the unaffected individuals. The propositus, an 18-yr-old boy, suffered from recurrent crises of hemolytic anemia and leg ulcers. A splenectomy was performed and the leg ulcer was treated un-successfully with a pinch graft. Studies ondialyzed hemolysates showed that the enzyme was kinetically abnorma, being almost entirely resistant to activation by fructose diphosphate. THE THERMOSTABILITY OF THE ENZYME WAS MODERATELY DECREASED, AND THE ELECTROPHORETIC MOBILITY WAS NORMAL. One may speculate that the development of leg ulcers in some kinships with PK deficiency may be related to variants of PK which exert unusual effects on the rheologic properties of the red cell in vivo.