Fatal infantile glycogen storage disease

Abstract

A girl with congenital limb weakness, mental retardation, and corneal ulceration died with respiratory insufficiency at age 4 years. Histochemistry of muscle biopsy showed only nonspecific myopathy, but electronmicroscopy revealed subsarcolemmal and intramyofibrillar accumulation of glycogen. Biochemical studies showed increased glycogen content of muscle with lack of phosphofructokinase. Phosphorylase b kinase activity was about 30% of normal. The relationship of the double enzyme deficiency to this unusual clinical picture is unclear.

Juvenile-onset permanent weakness in muscle phosphofructokinase deficiency

“…This so-called out-of-wind phenomenon, appears because the metabolic block occurs below the entry of glucose into glycolysis, whereas in McArdle disease, sugar intake ameliorates symptoms because the metabolic block is upstream of glucose metabolisms (second-wind phenomenon) [13]. In addition to the typical form of PFK deficiency, three other variants have been reported with onset in infancy [14][15][16][17], middle life [18] or late adult life [5,[19][20][21][22] and characterized by progressive fixed weakness. In the infantile form patients present with congenital hypotonia, severe progressive myopathy, but also other features like arthrogryposis congenita or signs of multisystem involvement, including seizures, cortical blindness, corneal opacifications, and cardiomyopathy [4].…”

Muscle glycogenosis with low phosphorylase kinase activity: mutations in PHKA1, PHKG1 or six other candidate genes explain only a minority of cases

“…50 Several cases with concurrent low activities of Phk and phosphofructokinase or debranching enzyme have also been described. 17,19 Three of our six patients, however, were analysed for activities of other multiple enzymes known to cause glycogen storage disease (see Subjects and methods) and all activities were normal. A primary deficiency of one of the remaining glycolytic enzymes not analysed or, for example, of a transporter mediating the release of lactate or alanine from glycolytically active muscle, 51,52 remains possible.…”

Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency.

“…These cases can be divided into five major groups, according to clinical symptoms and laboratory findings: group I, patients with the "classic" syndrome, i.e., simultaneous presence of myopathy and hemolysis (7,16,(30)(31)(32); group II, patients with isolated myopathy (33)(34)(35) only (9,11,13,36,37); group IV, individuals who are completely asymptomatic despite partial deficiency of erythrocyte PFK (14,38); group V, patients with progressive, fatal myopathy associated with other atypical features (39,40). Since only a few cases have been investigated in detail, the clinical classification of some of these syndromes remains uncertain and the nature of the underlying enzymatic defects unknown.…”