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Muscle phosphofructokinase deficiency in two generations
M Vorgerd1, J Karitzky, M Ristow
1Department of Neurology, Ruhr University Bochum, BG-Kliniken Bergmannsheil, Germany.
Abstract:
Phosphofructokinase (PFK) is the key regulatory enzyme of glycolysis. Patients lacking the muscular isoform of PFK typically present with myopathy and compensated hemolysis (glycogenosis type VII or Tarui's disease). Since 1965 about 30 cases of muscular PFK deficiency have been reported. In most cases family history suggests a recessive inherited trait. We describe a family of Ashkenazi Jewish origin with two members in subsequent generations suffering from muscular PFK deficiency. The propositus, a 19-year-old male patient presented with weakness, myalgias and exercise intolerance since early infancy. His father also had early fatigue on exercise with myalgias; the mother and a 12-year-old brother were asymptomatic. Muscle biopsy of both the propositus and his father showed increased glycogen storage and absent histochemical stain for PFK. Biochemical studies of muscle revealed a markedly decreased PFK activity and DNA analysis of the muscle PFK gene revealed compound heterozygosity in both cases. This is the first description of proven muscle PFK deficiency (glycogenosis type VII) in two subsequent generations.
Insights
This study details muscular phosphofructokinase (PFK) deficiency, a rare genetic disorder, in two generations of an Ashkenazi Jewish family. It highlights the enzyme
Area of Science:
- Biochemistry
- Genetics
- Enzymology
Background:
- Muscular phosphofructokinase (PFK) deficiency, also known as glycogenosis type VII or Tarui's disease, is a rare inherited metabolic disorder.
- It results from a deficiency in the muscular isoform of PFK, a key regulatory enzyme in glycolysis, leading to myopathy and hemolysis.
- Approximately 30 cases have been reported since 1965, typically exhibiting an autosomal recessive inheritance pattern.
Observation:
- A consanguineous family of Ashkenazi Jewish descent presented with two affected members across successive generations.
- The propositus and his father exhibited symptoms including weakness, myalgias, and exercise intolerance.
- Muscle biopsies revealed increased glycogen storage and absent PFK histochemical staining in both affected individuals.
Findings:
- Biochemical analyses confirmed markedly decreased PFK activity in muscle tissue.
- DNA analysis identified compound heterozygosity for mutations in the muscle PFK gene in both affected father and son.
- This represents the first documented instance of proven muscular PFK deficiency in multiple generations of a single family.
Implications:
- This case expands the understanding of the genetic heterogeneity and inheritance patterns of glycogenosis type VII.
- It underscores the importance of considering genetic factors and family history in diagnosing rare metabolic myopathies.
- Further research into PFK gene mutations and their clinical manifestations can aid in improved diagnostics and potential therapeutic strategies.