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Metabolic myopathies - PubMed

Review

Metabolic myopathies

Alejandro Tobon. Continuum (Minneap Minn). 2013 Dec.

Abstract

Purpose of review: The metabolic myopathies result from inborn errors of metabolism affecting intracellular energy production due to defects in glycogen, lipid, adenine nucleotides, and mitochondrial metabolism. This article provides an overview of the most common metabolic myopathies.

Recent findings: Our knowledge of metabolic myopathies has expanded rapidly in recent years, providing us with major advances in the detection of genetic and biochemical defects. New and improved diagnostic tools are now available for some of these disorders, and targeted therapies for specific biochemical deficits have been developed (ie, enzyme replacement therapy for acid maltase deficiency).

Summary: The diagnostic approach for patients with suspected metabolic myopathy should start with the recognition of a static or dynamic pattern (fixed versus exercise-induced weakness). Individual presentations vary according to age of onset and the severity of each particular biochemical dysfunction. Additional clinical clues include the presence of multisystem disease, family history, and laboratory characteristics. Appropriate investigations, timely treatment, and genetic counseling are discussed for the most common conditions.

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Figures

Figure 3-1.
Figure 3-1.

Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK = creatine kinase; PYGM = muscle isoform of glycogen phosphorylase; PPL = myophosphorylase; GSD = glycogen storage disease; PFK = phosphofructokinase; PGK = phosphoglycerate kinase; PGAM = phosphoglycerate mutase; COX = cytochrome c oxidase; RRF = ragged red fibers; mtDNA = mitochondrial DNA; nDNA = nuclear DNA; CPT = carnitine palmitoyl transferase; VLCAD = very long chain acyl coenzyme A dehydrogenase. Modified from Berardo A, et al. Curr Neurol Neurosci Rep. © 2010, with permission from Springer Science + Business Media.

link.springer.com/article/10.1007/s11910-010-0096-4

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Figure 3-2.
Figure 3-2.

Glycolytic pathways. Glycogen storage diseases (GSDs) are designated with Roman numerals. GSD I and VI are not included since they do not cause muscle disease. The numerals denote defects in the following enzymes: II, acid maltase; III, debrancher; IV, brancher; V, myophosphorylase; VII, phosphofructokinase; VIII, phosphorylase b kinase; IX, phosphoglycerate kinase; X, phosphoglycerate mutase; XI, lactate dehydrogenase; XII, aldolase A; XIII, beta enolase, XIV, phosphoglucomutase 1. cAMP = cyclic adenosine monophosphate; UDPG = uridine diphosphoglucose; PLD = phosphorylase-limit dextrin; TPI = triose phosphate isomerase.

Figure 3-3.
Figure 3-3.

Acid maltase deficiency. Nonrimmed vacuoles in muscle fibers due to glycogen deposition. A, Hematoxylin and eosin stain; B, Acid phosphatase stain. Courtesy of Derek A. Mathis, MD.

Figure 3-4.
Figure 3-4.

Myophosphorylase deficiency. Hematoxylin eosin stain demonstrates subsarcolemmal vacuoles (A), immunohistochemical analysis for myophosphorylase confirms its absence (B), compared with normal control (C). Courtesy of Derek A. Mathis, MD.

Figure 3-5.
Figure 3-5.

Schematic illustration of the oxidation of fatty acids in mitochondria. Short- and medium-chain fatty acids (SMCFA) freely cross the mitochondrial membrane, whereas long-chain fatty acids (LCFA) require a specific transporter system. Acyl coenzyme A (acyl-CoA) synthetase transforms the LCFA into acyl-CoA, and the coenzyme A (CoA) is exchanged for carnitine by carnitine palmitoyltransferase I (CPT I). Acylcarnitine is then transported across the inner mitochondrial membrane by carnitine acylcarnitine translocase (CAT). Carnitine is removed from acylcarnitine by carnitine palmitoyltransferase II (CPT II) to form acyl-CoA, which can undergo beta oxidation. Modified with permission from van Adel BA, Tarnopolsky MA, J Clin Neuromuscul Dis. © 2009, Lippincott Williams & Wilkins.

journals.lww.com/jcnmd/Abstract/2009/03000/Metabolic_Myopathies__Update_2009.3.aspx

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Figure 3-6.
Figure 3-6.

Ragged red fibers revealed by the modified Gomori one-step trichrome stain (A) and combined cytochrome oxidase/succinate dehydrogenase stain (B). They are formed by the subsarcolemmal accumulation of abnormal mitochondria. Courtesy of Derek A. Mathis, MD.

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