Diagnostic challenges in metabolic myopathies

ABSTRACT

Introduction

Metabolic myopathies comprise a clinically etiological diverse group of disorders caused by defects in cellular energy metabolism including the breakdown of carbohydrates and fatty acids, which include glycogen storage diseases and fatty acid oxidation disorders.

Their wide clinical spectrum ranges from infantile severe multisystemic disorders to adult-onset myopathies. To suspect in adults these disorders, clinical features such as exercise intolerance and recurrent myoglobinuria need investigation while another group presents fixed weakness and cardiomyopathy as a clinical pattern.

Areas covered

In metabolic myopathies, clinical manifestations are important to guide diagnostic tests used in order to lead to the correct diagnosis. The authors searched in literature the most recent techniques developed. The authors present an overview of the most common phenotypes of Pompe disease and what is currently known about the mechanism of ERT treatment. The most common disorders of lipid metabolism are overviewed, with their possible dietary or supplementary treatments.

Expert commentary

The clinical suspicion is the clue to conduct in-depth investigations in suspected cases of metabolic myopathies that lead to the final diagnosis with biochemical molecular studies and often nowadays by the use of Next Generation Sequencing (NGS) to determine gene mutations.

KEYWORDS:

• Glycogenosis type 2
• Pompe disease
• carnitine
• riboflavin
• fatty acid oxidation
• glycogenosis type 5
• newborn screening
• biomarkers

Article highlights

• A debated issue is when to start and when to stop ERT in LOPD. Recent European guidelines have been prepared by the EPOC consortium.

• New diagnostic techniques are available in metabolic disorders such as the use of DBS and NGS.

• A regular exercise protocol is beneficial in Mc Ardle disease patients. The main precautionary guideline in FAO defects of mitochondrial beta-oxidation is the avoidance of fasting.

• Since patients with metabolic disorders cannot utilize fatty acids, the accumulation of toxic intermediate metabolites (i.e. Acyl-CoAs) should be avoided to present development of the critical signs. In FAO defects the dietary fat consumption should be restricted to 25% of total calories, and the amount of long-chain fatty acids should be minimal. An increased caloric intake from carbohydrates may be necessary during intermittent illness attacks because of the increased metabolic request. A low – fat diet is used in PCD, MADD, and CPT II patients [94] and shows that these defects are rare but treatable.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by AFM-Telethon 22392 grant and Biobank BBMRNR, part of the BBMRI-ERIC network.