First description of phosphofructokinase deficiency in spain: identification of a novel homozygous missense mutation in the PFKM gene

Joan-Lluis Vives-Corrons,Pavla Koralkova,Maria Del Mar Mañú Pereira,Josep M Grau,Richard Van Wijk

doi:10.3389/fphys.2013.00393

Joan-Lluis Vives-Corrons, Pavla Koralkova + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2013.00393

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Abstract

Phosphofructokinase deficiency is a very rare autosomal recessive disorder, which belongs to group of rare inborn errors of metabolism called glycogen storage disease. Here we report on a new mutation in the phosphofructokinase (PFK) gene PFKM identified in a 65-years-old woman who suffered from lifelong intermittent muscle weakness and painful spasms of random occurrence, episodic dark urines, and slight haemolytic anemia. After ruling out the most common causes of chronic haemolytic anemia, the study of a panel of 24 enzyme activities showed a markedly decreased PFK activity in red blood cells (RBCs) from the patient. DNA sequence analysis of the PFKM gene subsequently revealed a novel homozygous mutation: c.926A>G; p.Asp309Gly. This mutation is predicted to severely affect enzyme catalysis thereby accounting for the observed enzyme deficiency. This case represents a prime example of classical PFK deficiency and is the first reported case of this very rare red blood cell disorder in Spain.

Highlights

Phosphofructokinase (ATP: D- fructose-6-phosphate-1phosphotransferase; EC 2.7.1.11; PFK) is a key regulatory enzyme of the glycolytic cycle and catalyses the conversion of fructose-6-phosphate to fructose-1,6-diphosphate (Figure 1)
PFK-M is the sole subunit in muscle cells whereas red blood cells (RBCs) contain both L and M subunits and form their hybrids (M4, L4, M3L, M2L2, and ML3)
We describe here a Spanish patient with a clinical history of anemia, haemolysis, and intermittent muscle weakness, who was found to be homozygous for a novel mutation in the PFKM gene (c.926A>G)

Summary

INTRODUCTION

Phosphofructokinase (ATP: D- fructose-6-phosphate-1phosphotransferase; EC 2.7.1.11; PFK) is a key regulatory enzyme of the glycolytic cycle and catalyses the conversion of fructose-6-phosphate to fructose-1,6-diphosphate (Figure 1). We describe here a Spanish patient with a clinical history of anemia, haemolysis, and intermittent muscle weakness, who was found to be homozygous for a novel mutation in the PFKM gene (c.926A>G). This mutation encodes the substitution of aspartic acid by glycine at residue 309 (p.Asp309Gly). DNA sequence analysis of individual exons of PFKM, including flanking splice sites, revealed that the patient was homozygous for a missense mutation in exon 11: c.929A>G This mutation, that has not been previously reported in the literature, encodes the substitution of aspartic acid by glycine at residue 309 (p.Asp309Gly). Muscle biopsy showed slight amounts of polysaccharide (PAS) not digested by diastase and abnormalities in NADH-TR reaction

DISCUSSION

Findings

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