Rhabdomyolysis as a Presenting Manifestation of Very Long-Chain Acyl-Coenzyme a Dehydrogenase Deficiency

Abstract

Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (MIM 201475) is a rare inherited disorder with three forms of clinical presentation: a severe early-onset form; an intermediate form with childhood onset; and an adult-onset form, of mild severity. During adolescence and adulthood, exercise intolerance, myalgia and recurrent episodes of rhabdomyolysis are the main clinical features. The authors present a case of a 13-year old female, with severe myalgia and dark urine after prolonged exercise. Analytical evaluation showed marked elevation plasma creatine kinase and myoglobin. The increased levels of tetradecenoyl carnitine in patient’s dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. Family history is remarkable for first grade consanguinity of parents and a 19-year old brother with records of repeated similar episodes after moderate intensity physical efforts which was subsequently also diagnosed with VLCAD deficiency. This is one of the first cases of late-onset of disease diagnosed in Portugal.

Clinical manifestations and management of fatty acid oxidation disorders

“…Elevated plasma creatine kinase and myoglobin, for example following prolonged exercise, are indicative of rhabdomyolysis and suggestive of possible underlying FAOD [21]. Currently, the pathogenesis of rhabdomyolysis among individuals with FAOD is poorly understood [71].…”

“…As the disease progresses, progressive or episodic muscle weakness, muscle pain (myalgia), chronic fatigue, exercise intolerance, and rhabdomyolysis may occur [15,26]. Patients with FAOD who present with rhabdomyolysis have reported generalized muscle pain in conjunction with dark urine, most commonly following periods of intense exercise [21].…”

Investigating the genetic susceptibility to exertional heat illness

“…This individual also harboured a p.T538M variant in ATP2A1 (annotated benign by GAVIN). Three variants were identified in the ACADVL gene, which encodes a mitochondrial enzyme, very long-chain acyl-CoA dehydrogenase (VLCAD) 51. ACADV L p.V283A (annotated VUS by GAVIN), which co-segregated with the IVCT phenotype alongside RYR1 p.R3539H (figure 1A), has been previously associated in the homozygous form with VLCAD deficiency in a number of unrelated families 52 53…”

Fasting-Induced Rhabdomyolysis in An Adolescent Girl

“…Creatine kinase levels are typically markedly elevated, and muscle pain and myoglobinuria may be present. Differential diagnosis in children usually consists of infections, trauma, heavy exercise, toxins, genetic and inflammatory myopahties and metabolic diseases [4,7].…”

“…Metabolic myopathies should be suspected when recurrent episodes of rhabdomyolysis after exertion or in association with fasting or a viral illness are present. The last two associations occur most commonly with carnitine palmitoyl transferase II deficiency and the other disorders of lipid metabolism [7,1]. Recognized heritable causes of rhabdomyolysis are defects in the glycogen metabolism and glycolysis, in the respiratory chain or in fatty acid oxidation [5,8].…”