272 14 Diseases of Muscle (Myopathies)

Metabolic Myopathies

Normal muscle function depends on an adequate supply and continuous regeneration of the energetic molecule ATP. ATP can be derived from a number of different sources; glycogen and lipid metabolism, and normal mitochondrial function, play a central role in these processes. Insufficient availability of energy to muscle tissue results in ex- ercise-induced muscle weakness, myalgias, and, in the later course of disease, contractures. The underlying metabolic disorder is usually due to an inherited enzyme defect. The major clinical entities of this type are the glycogenoses, carnitine deficiency, and the group of mitochondrial (en- cephalo-)myopathies (with dysfunction either of the tricarbonic acid cycle, or of the respiratory chain and oxidative phosphorylation).

These metabolic diseases often do not become apparent until adolescence or young adulthood. The following findings suggest the presence of one of these conditions:

Muscle exercise is followed by muscle weakness, myalgias, and/or contractures. Rhabdomyolysis sometimes occurs, causing myoglobinuria and an elevated CK concentration.

Permanent muscle atrophy and weakness may develop over time.

The serum CK concentration is often elevated and sometimes the lactate concentration as well (particularly in mitochondrial diseases).

The EMG is usually normal; only in rare cases is there any evidence of myopathy.

Muscle exercise under ischemic conditions normally leads to a fourfold rise of the lactate concentration. This rise does not occur in persons suffering from one of the glycogenoses. If, on the other hand, an exaggerated rise is found after only mild exertion, a mitochondrial disease is probably present.

The individual types of metabolic myopathy are summarized in Table 14.5. In the following paragraphs, we will discuss only rhabdomyolysis and the mitochondrial encephalomyopathies in detail.

Acute Rhabdomyolysis

Rhabdomyolysis is the acute destruction of skeletal muscle tissue, resulting in the passage of myoglobin into the bloodstream and a marked rise of the serum CK concentration. There are both idiopathic forms, with an autosomal dominant inheritance pattern, and symptomatic forms of rhabdomyolysis, caused either by toxic in- fluences—e. g., the consumption of alcohol, heroin, or certain medications, such as statins—or by a disease of muscle metabolism, e. g., one of the glycogenoses. Rhabdomyolysis can thus be the symptomatic expression of a wide variety of pathological processes.

Clinical manifestations. The patient develops rapidly worsening muscle pain and weakness. Examination reveals loss of reflexes and often muscle swelling; urinalysis reveals myoglobinuria. There is no sensory deficit. The most feared complication is acute renal failure.

Treatment. If the patient has myoglobinuria, optimal hydration is given to prevent renal failure. If renal failure nevertheless occurs, dialysis is necessary.

Mitochondrial Encephalomyopathies

Mitochondrial function. Mitochondria are present in every cell of the body; they are the sites of pyruvate, fatty acid, and amino acid metabolism. These processes result in the production of ATP, an essential energy carrier for cellular metabolism and muscle contraction.

Table 14.5 Metabolic myopathies with exercise-induced manifestations

Group of diseases	Enzyme defect	Clinical manifestations	Diagnostic evaluation
Glycogen metabo-	phosphorylase	exercise-induced weakness, myal-	lactate ischemia test
lism	phosphorylase kinase	gias, contractures, and sometimes	electromyography
	phosphofructokinase	myoglobinuria, even after brief ex-	muscle biopsy with histochemistry
	phosphoglycerate kinase	ertion	biochemical study of muscle
			DNA analysis
Lipid metabolism	carnitine deficiency	exercise-induced weakness, myal-	muscle biopsy with histochemistry
	carnitine palmitoyl transferase	gias, and sometimes myoglo-	and perhaps biochemical analysis;
	deficiency	binuria, with prolonged muscle	in carnitine deficiency, the serum
		activity	carnitine concentration is low
Mitochondrial	decoupling of oxidative phosphoryla-	muscle involvement almost always	serum lactate concentration,
myopathies	tion	includes progressive external oph-	muscle biopsy with electron micro-
	defects of the tricarbonic acid cycle	thalmoplegia; the brain is usually	scopy and biochemical analysis,
	defects of the respiratory chain	involved as well	DNA analysis
Purine nucleotide	myoadenylate deaminase	rarely clinically relevant, exercise	absence of rise in ammonia con-
cycle		intolerance	centration with exercise

Mumenthaler / Mattle, Fundamentals of Neurology © 2006 Thieme All rights reserved. Usage subject to terms and conditions of license.