A Diagnostic Algorithm for Metabolic Myopathies

Abstract

Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1).

Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin

“…Recurrent rhabdomyolysis may be caused by mutations in other genes, including other muscle forms of GSDs, as well as disorders of fatty acid oxidation and mitochondrial respiratory chain disorders. 18 DNA from this patient was analyzed using MPS for a group of 24 genes responsible for metabolic myopathy. Of note, a heterozygous c.1784delC (p.Ala596Glnfs*2) frameshift mutation and a heterozygous c.122C>T (p.Pro41Leu) novel missense variant in the CPT2 gene were detected.…”

Tarui´s disease: Review and bioinformatic perspectives

“…Como se mencionó previamente, algunos casos específicos pueden afectar bazo, corazón y otros órganos (4). Por ejemplo, cuando hay ausencia de actividad maltasa ácida en la enfermedad de Pompe (Tipo II) hay afectación de casi todos los órganos, incluyendo al corazón (2,4).…”

“…La producción de energía se da a través de la glicólisis, en la que la glucosa es degradada hasta producir ATP (adenosina trifosfato), la moneda energética, además de piruvato y NADH (dinucleótido de nicotinamida y adenina) que pueden continuar a ciclo de Krebs o a respiración anaerobia. Cuando las necesidades energéticas han sido satisfechas, diversos mecanismos regulatorios permiten el almacenamiento del exceso de glucosa en forma de glucógeno, en un proceso llamado gluconeogénesis (1,2). La gluconeogénesis, la glucogenólisis y la glucólisis son procesos celulares que son mediados por enzimas y altamente regulado, tanto por los mismos carbohidratos como por otros tipos de moléculas.…”

“…La gluconeogénesis, la glucogenólisis y la glucólisis son procesos celulares que son mediados por enzimas y altamente regulado, tanto por los mismos carbohidratos como por otros tipos de moléculas. La deficiencia parcial o total de la actividad enzimáti-ca en las reacciones de dichos procesos se constituyen como un grupo de trastornos del metabolismo llamados enfermedades del almacenamiento del glucógeno (EAG) (2). Si la afectación de estos procesos es de forma directa en las enzimas, la enfermedad se denomina enfermedad primaria, mientras que si la alteración es por medio de reguladores de su metabolismo, entonces se llaman enfermedades secundarias (3).…”

Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis

“…Published testing algorithms can aid in focusing molecular testing by distinguishing mitochondrial disorders from other metabolic disturbances as well as from each other. 9,10 Once mutations are identified in an individual affected with a recessive disorder, it becomes even more pertinent to verify a chromosomal trans configuration (the phase) by parental testing. As mutations in multiple different genes may cause similar phenotypes, and heterozygous individuals may under certain circumstances be symptomatic, it is crucial that the genotype of a patient with a mitochondrial disorder be unambiguously established.…”