Related Experiment Videos
Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency
R Amit1, N Bashan, J M Abarbanel
1Department of Pediatrics, Soroka Medical Center Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Jerusalem, Israel.
Insights
A rare genetic disorder caused progressive muscle weakness and cardiomyopathy in infants due to reduced phosphofructokinase-1 (PFK-1) activity. This multisystem enzyme deficiency suggests a potential unknown activator may be involved.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Medicine
Background:
- A consanguinous Bedouin family presented with a history of fatal early-onset progressive generalized muscle weakness and cardiomyopathy in two children.
- The affected siblings exhibited similar clinical phenotypes, with the older brother dying at 21 months of age.
Observation:
- Infant presented with progressive generalized muscle weakness.
- Muscle biopsies revealed nonspecific myopathic changes.
- Postmortem studies showed excessive extralysosomal glycogen storage and reduced phosphofructokinase-1 (PFK-1) activity in heart and liver.
Findings:
- Reduced PFK-1 activity identified in both muscle and liver tissues.
- Separate chromosomal locations of PFK-1 genes preclude a single mutation explanation.
- Normal 6-phosphofructose-2-kinase (PFK-2) activity in the liver.
Implications:
- Suggests a potential deficiency of an unknown activator common to all PFK-1 isozymes.
- Highlights a possible novel mechanism for multisystem enzyme deficiency disorders.
- Underscores the complexity of inherited metabolic myopathies and cardiomyopathies.
Abstract:
An infant girl of consanguinous Bedouin parents suffered from fatal early onset of progressive generalized muscle weakness. Her older brother suffered from similar weakness and cardiomyopathy, which led to his death at the age of 21 months. A muscle biopsy performed on the propositus at the age of 9 months was PAS-negative, and showed nonspecific myopathic changes. A second muscle biopsy, performed at 21 months of age, a few days before her death, and postmortem study of heart and liver, disclosed excessive extralysosomal glycogen storage and reduced phosphofructokinase-1 (PFK-1) activity. Because the genes encoded for PFK-1 in liver and muscle are located on separate chromosomes, the reduced enzyme activity in both tissues could not be related to a single mutation for this enzyme. Activity of 6-phosphofructose-2-kinase (PFK-2), a recently discovered physiological activator to all PFK-1 isozymes, was normal in the liver. The possibility that this multisystem PFK-1 deficiency may be related to the absence of a yet unknown activator, common to all PFK-1 isozymes, is discussed.