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Metabolic and endocrine disorders 

Metabolic and endocrine disorders

Metabolic and endocrine disorders

David Hilton-Jones

and Richard Edwards



New, simple, diagnostic test for acid maltase deficiency.

Recent developments concerning statins and muscle disease.

A relevant case history from Neurological Case Histories: Case Histories in Acute Neurology and the Neurology of General Medicine has been added to this chapter.

Updated on 28 Nov 2012. The previous version of this content can be found here.
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date: 30 March 2017

Disturbances of the biochemical or ionic balance of muscle resulting in impaired muscle function can be caused by a disparate group of conditions, including primary inherited disorders affecting enzymes or ion channels, and secondary disorders in which metabolic or endocrine disequilibrium disturbs normal function.

Primary metabolic myopathies

The primary metabolic myopathies are mostly autosomal recessive disorders in which lack of activity of a specific enzyme impairs ATP generation. Clinical presentation is with exercised-induced symptoms, but there are fundamental differences in manifestations depending upon whether the enzyme defect affects glycogen/glucose metabolism or fatty acid metabolism, reflecting the very different contributions that these pathways make to energy production depending on the nature of the exercise.

Disorders of glycogen and glucose metabolism—these include: (1) Myophosphorylase deficiency (Mc Ardle’s disease)—the commonest (but still very rare) glycogenosis; symptoms usually start in childhood, but are often not recognized at that time; cardinal features are pain, weakness, and stiffness of muscles early in exercise, relieved by rest; strenuous exercise may precipitate rhabdomyolysis and acute kidney injury. Diagnosis is established by histochemical demonstration of the absence of phosphorylase staining (or by enzyme assay) on muscle biopsy, or by genetic studies. There is no specific treatment. (2) Acid maltase deficiency—typically presents with a slowly progressive, painless, proximal myopathy; diaphragmatic involvement is common and can lead to presentation with respiratory failure; there are no exercise-induced symptoms. Enzyme replacement therapy may benefit some patients. (3) Other conditions—these include debrancher enzyme deficiency and phosphofructokinase deficiency.

Disorders of fatty acid metabolism—these include: (1) Carnitine palmitoyltransferase deficiency—symptoms are precipitated by sustained exercise (e.g. long-distance running) or prolonged fasting, and severe episodes may precipitate rhabdomyolysis and acute kidney injury; diagnosis requires enzyme assay; treatment with a high carbohydrate, low fat diet may reduce the number of attacks. (2) Other conditions—numerous defects of β‎-oxidation.

Secondary metabolic and endocrine myopathies

Endocrine myopathies—nearly all forms of endocrine disturbance can be associated with weakness, typically relatively mild and involving the proximal muscles. The commonest are Cushing’s syndrome (including iatrogenic steroid excess), and hypo- and hyperthyroidism. Weakness resolves when the hormone imbalance is corrected.

Disorders of calcium, vitamin D, and parathyroid hormone metabolism—myopathy is a feature of osteomalacia, primary hyperparathyroidism, renal osteodystrophy, dialysis osteodystrophy and ischaemic myopathy.

Other conditions—(1) Alcohol excess—alcoholics frequently have muscle weakness, but it is often unclear whether the primary cause is myopathic or neuropathic. Alcoholic rhabdomyolysis typically follows a binge. (2) Drug-induced myopathies—the most common cause seen in clinical practice is statins.

Skeletal muscle channelopathies

These rare inherited disorders affect muscle membrane ion channels, resulting in altered electrical characteristics: (1) period paralysis—underlying mutations affect either the sodium or calcium channels; manifest with episodic weakness; (2) myotonic dystrophies—see Chapter 24.24.3; (3) malignant hyperthermia—caused by mutations in the calcium channel associated ryanodine receptor; muscle relaxants and anaesthetic agents may trigger generalized muscle contraction with rapid rise in body temperature that can be fatal if untreated.

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