Phosphorylase kinase deficiency

In liver phosphorylase deficiency (glycogenosis type VI, Hers disease Fig. 42-1) and in two genetic forms of phosphorylase kinase deficiency, one of which is X-linked recessive, the other of which is autosomal recessive, hypoglycemia is either absent or mild. Symptoms of brain dysfunction do not usually occur (type VIII, Fig. 42-1) [1],... 

Type VI/Hers hepatomegaly, mild hypoglycemia, hyperlipidemia, and ketosis symptoms improve with age Type IX/phosphorylase kinase deficiency similar to type VI presentation (X-linked)... 

Lederer B, Van Hoof F, Van den Berghe G, Hers HG (1975) Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen storage disease. A study of phosphorylase kinase deficiency. Biochem J 147 23-35... 

D-l) Liver phosphorylase kinase deficiency (Type Vm GSD). The defect in this enzyme prevents activation of liver phosphorylase (see fig. 3.2). There is accumulation of glycogen in the liver and liver enlargement. Diagnosis is made on assay for the defective enzyme in liver biopsy or in leukocytes or erythrocytes. 

Type VI (Liver Phosphorylase or Phosphorylase Kinase Deficiency)... 

Table 15.15. Glycogen storage disease type 9 (liver phosphorylase kinase deficiency) ...

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

Type VIII Deficiency of liver phosphorylase kinase As for type VI. 

In GSD IX (phosphorylase b-kinase deficiency), amylo-l,6-glucosidase activity in RBC is usually elevated. 

Besley GTN (1987) Phosphorylase b kinase deficiency in glycogenosis type VIII differentiation of different phenotypes and heterozygotes by erythrocyte enzyme assay. J Inherit Metab Dis 10 115-118... 

H21. Hug, G, Schubert, W. K., and Chuck, G., Deficient activity of dephospho-phosphorylase kinase and accumulation of glycogen in the liver, J. Clin. Invest. 48, 704-715 (1969). 

Erythrocytes from a child with purine nucleoside phosphorylase (PNP) deficiency (Watson et al - this symposium) and high levels of inosine and guanosine, deoxyinosine and deoxyguanosine in plasma and urine do not show intracellular accumulation of any of these nucleosides. The finding of high intracellular levels of dAR in the ADA deficient erythrocyte is thus in accord with a unique transport system for adenosine-type compounds associated with both adenosine kinase (AK) and ADA in the human red cell. 

More recently a case was described [127] in which the total activity of phosphorylase in both muscle and liver was normal, but the enzyme was in the inactive form. Evidence was obtained for a deficiency of the cyclic 3, 5 -AMP-dependent kinase which phosphorylates phosphorylase kinase which, in turn, converts inactive phosphorylase b to active phosphorylase a. 

Phosphorylase b-kinase is the enzyme deficient in glycogenosis type IX (GSD IX, formerly GSD VIII, MIM 306 000). 

Hepatic glycogenosis (type VI) (G.H. Hers, 1959) is due to hepatic phosphorylase deficiency. Subtype Via is caused by a lack of phos-phorylase-B kinase, and it is transmitted by the x-chromosomal recessive route. Subtype Vib shows a deficiency in glycogen phosphorylase, and its transmission is autosomal recessive. In the musculature, the analogous enzyme is, however, intact. Nevertheless, there is pronounced genetic and phenotypical heterogeneity. 

Carson, D.A. Kaye, J. Seegmiller, J.E. Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency possible role of nucleoside kinase(s). Proc. Natl. Acad. Sci. USA, 74, 5677-5681 (1977)... 

Adenosine serves as a carbon source for mammalian cells by its deamination to inosine in the presence of ADA, the cleavage of inosine to hypoxanthine and ribose-l-P in the presence of purine nucleoside phosphorylase, the conversion of ribose-l-P to ribose-5-P in the presence of phosphopentomutase and then the entrance of ribose-5-P into the glycolytic cycle. To insure that adenosine utilization is mediated by ADA and to avoid the inhibitory effects of adenosine on cell growth, a tubercidin resistant mutant (tub ) deficient in adenosine kinase activity was selected initially. 

The deficient enzyme in this case is phosphorylase b-kinase, the enzyme involved in the activation of phosphorylase. 

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