PGK deficiency

Abstract

Summary Phosphoglycerate kinase (PGK) deficiency is one of the relatively uncommon causes of hereditary non‐spherocytic haemolytic anaemia (HNSHA). The gene encoding the erythrocyte enzyme PGK1, is X‐linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations. Twenty‐six families have been described and in 20 of these the mutations are known. The reason for different clinical manifestations of mutations of the same gene remains unknown.

A novel <i>PGK1</i> mutation associated with neurological dysfunction and the absence of episodes of hemolytic anemia or myoglobinuria

“…anemia (followed by recurrent hemoglobinuria caused by rhabdomyolysis), intellectual disability, and seizures (1). In Table 1, previously reported PGK1 mutations are summarized (1)(2)(3). Some patients exhibited symptoms only in the CNS and the muscles, but not in the RBC (24).…”

“…Phosphoglycerate kinase (PGK) deficiency is a rare cause of congenital hemolytic anemia (1). Mutations in the phosphoglycerate kinase 1 gene (PGK1) result in an X-linked recessive disorder (MIM #311800) involving three tissues: red blood cells (RBC), the central nervous system (CNS), and muscles (2).…”

A new variant of phosphoglycerate kinase deficiency (p.I371K) with multiple tissue involvement: Molecular and functional characterization

“…It catalyzes the reversible phosphoryl transfer between 1,3-bisphosphoglycerate (1,3-BPG) and MgADP to form 3-phosphoglycerate and MgATP in the presence of free magnesium [1]. Moreover, PGK was also shown to participate in the DNA replication and repair in mammal cell nuclei [2]; finally, extracellular PGK has been recently reported to exhibit thiol reductase activity on plasmin, thus regulating tumor angiogenesis [3,4].…”

Clinical Severity of PGK1 Deficiency Due To a Novel p.E120K Substitution Is Exacerbated by Co-inheritance of a Subclinical Translocation t(3;14)(q26.33;q12), Disrupting NUBPL Gene

“…Although rare, lethal forms of PGK1 deficiency during infancy have been reported in the literature (Beutler 2007). Even more infrequent are PGK1-deficient patients exhibiting the three distinguishing clinical features of this deficiency (hereditary non-spherocytic hemolytic anemia, neurological dysfunction, and myopathy).…”

“…PGK1 deficiency (OMIM #300653) is an X-linked recessive condition characterized by variable clinical manifestations involving up to three different tissues, i.e., red blood cells (RBC), skeletal muscle, and neurological tissue. However, patients rarely show all three clinical features (Beutler 2007;Chiarelli et al 2012). To date, 22 different mutations have been identified in PGK1, and 17 of them have been characterized at the protein level Fermo et al 2012;Tamai et al 2014).…”