Adult-onset exercise intolerance due to phosphorylase b kinase deficiency

doi:10.1054/jocn.1999.0230

Journal of Clinical Neuroscience

Volume 8, Issue 3, May 2001, Pages 286-287

https://doi.org/10.1054/jocn.1999.0230 Get rights and content

Abstract

Muscle-specific phosphorylase b kinase deficiency is an unusual form of glycogen storage disorder. The majority of patients are male with an age at diagnosis between 15 to 36 years. Clinical features include exercise intolerance, myalgia and muscle weak ness. A forearm ischaemic exercise test is usually normal and histochemical staining for myophosphorylase positive. The demonstration of reduced muscle phosphorylase b kinase activity by biochemical assay confirms the diagnosis.

We report a 36 year old male with phosphorylase b kinase deficiency and symptom onset in adult life.

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Cited by (8)

Metabolic and mitochondrial myopathies
2014, Neurologic Clinics
Citation Excerpt :
A host of neuromuscular manifestations have been attributed to muscle PhK deficiency including exertional muscle pain and muscle cramps, with or without myoglobinuria,13–18 progressive proximal or distal weakness,14,15,19 and otherwise asymptomatic hyperCKemia.20,21 However, only 7 patients have had genetic confirmation of mutations in the PHKA1 gene17,18,21–24; serum CK and muscle glycogen levels have been reported as normal or elevated. Three patients with muscle PhK deficiency and confirmed PHKA1 mutations had minor and inconsistent limitations in lactate production with ischemic or cycle exercise testing.21
Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?
2008, Neurology
It is unclear to what extent muscle phosphorylase b kinase (PHK) deficiency is associated with exercise-related symptoms and impaired muscle metabolism, because 1) only four patients have been characterized at the molecular level, 2) reported symptoms have been nonspecific, and 3) lactate responses to ischemic handgrip exercise have been normal.
We studied a 50-year-old man with X-linked PHK deficiency using ischemic forearm and cycle ergometry exercise tests to define the derangement of muscle metabolism. We compared our findings with those in patients with McArdle disease and in healthy subjects.
Sequencing of PHKA1 showed a novel pathogenic mutation (c.831G>A) in exon 7. There was a normal increase of plasma lactate during forearm ischemic exercise, but lactate did not change during dynamic, submaximal exercise in contrast to the fourfold increase in healthy subjects. Constant workload elicited a second wind in all patients with McArdle disease, but not in the patient with PHK deficiency. IV glucose administration appeared to improve exercise tolerance in the patient with PHK deficiency, but not to the same extent as in the patients with McArdle disease. Lipolysis was higher in the patient with PHK deficiency than in controls.
These findings demonstrate that X-linked PHK deficiency causes a mild metabolic myopathy with blunted muscle glycogen breakdown and impaired lactate production during dynamic exercise, which impairs oxidative capacity only marginally. The different response of lactate to submaximal and maximal exercise is likely related to differential activation mechanisms for myophosphorylase.
GSD = glycogen storage disease; PHK = phosphorylase b kinase; RER = respiratory exchange rate.
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^f1: Correspondence to: Dr Dan Milder, Department of Neurology, Bankstown-Lidcombe Hospital, Eldridge Rd, Bankstown, NSW 2200, Australia. Tel.: +61 2 9722 8030; Fax: +61 2 977 8316.

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CommunicationsAdult-onset exercise intolerance due to phosphorylase b kinase deficiency

Abstract

Biochem Biophys Res Commun

Glycogen metabolism and glycogen storage diseases

Physiol Rev

McArdle's disease: molecular genetics and metabolic consequences of the phenotype

Muscle and Nerve

Glycolytic defects in muscle: aspects of collaboration between basic science and clinical medicine

Muscle and Nerve

Biochemistry and molecular genetics of human glycogenolysis: an overview

Muscle and Nerve

Clinical and biochemical features of 10 adult patients with muscle phosphorylase kinase deficiency

Neurology

Phosphorylase b kinase deficiency in man: a review

J Inher Metab Dis

Communications
Adult-onset exercise intolerance due to phosphorylase b kinase deficiency