Lactate production upon short-term non–ischemic forearm exercise in mitochondrial disorders and other myopathies

Hanisch, Frank; Eger, K.; Bork, Silke; Lehnich, Holger; Deschauer, Marcus; Zierz, Stephan

doi:10.1007/s00415-006-0101-7

Cited by 13 publications

(5 citation statements)

References 18 publications

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“…A suboptimal effort is reflected as a failure of both lactate and ammonia to rise following exercise. The sphygmomanometer cuff is not strictly necessary and rhythmic contraction per se is sufficient to yield good test sensitivity and specificity 54,55 . Consequently, a 1-minute nonischemic forearm exercise test is routinely used to lower the risk of rhabdomyolysis and acute compartment syndrome.…”

Section: Disorders Of Glycolysis/glycogenolysis (Glycogen Storage Dis...mentioning

confidence: 99%

Metabolic Myopathies

Tarnopolsky¹

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEW: Metabolic myopathies are disorders that affect skeletal muscle substrate oxidation. Although some drugs and hormones can affect metabolism in skeletal muscle, this review will focus on the genetic metabolic myopathies.RECENT FINDINGS: Impairments in glycogenolysis/glycolysis (glycogen storage disease), fatty acid transport/oxidation (fatty acid oxidation defects), and mitochondrial metabolism (mitochondrial myopathies) represent most metabolic myopathies; however, they often overlap clinically with structural genetic myopathies, referred to as pseudometabolic myopathies. Although metabolic myopathies can present in the neonatal period with hypotonia, hypoglycemia, and encephalopathy, most cases present clinically in children or young adults with exercise intolerance, rhabdomyolysis, and weakness. In general, the glycogen storage diseases manifest during brief bouts of high-intensity exercise; in contrast, fatty acid oxidation defects and mitochondrial myopathies usually manifest during longer-duration endurance-type activities, often with fasting or other metabolic stressors (eg, surgery, fever). The neurologic examination is often normal between events (except in the pseudometabolic myopathies) and evaluation requires one or more of the following tests: exercise stress testing, blood (eg, creatine kinase, acylcarnitine profile, lactate, amino acids), urine (eg, organic acids, myoglobin), muscle biopsy (eg, histology, ultrastructure, enzyme testing), and targeted (specific gene) or untargeted (myopathy panels) genetic tests. SUMMARY: Definitive identification of a specific metabolic myopathy often leads to specific interventions, including lifestyle, exercise, and nutritional modifications; cofactor treatments; accurate genetic counseling; avoidance of specific triggers; and rapid treatment of rhabdomyolysis.

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Section: Disorders Of Glycolysis/glycogenolysis (Glycogen Storage Dis...mentioning

confidence: 99%

Metabolic Myopathies

Tarnopolsky¹

2022

CONTINUUM: Lifelong Learning in Neurology

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“…Serum creatine kinase (CK) levels were extracted from the archived clinical files of patients (n = 33). In addition, levels of lactate and ammonia upon exercise were measured in 16 available patients according to the established forearm ischemic exercise test protocol [14,15]. The results were compared with those of 21 healthy controls (14 males, 7 females; mean age: 38 years).…”

Section: Laboratory Studiesmentioning

confidence: 99%

“…Recently, we had postulated that the increased ammonia production upon exercise in McArdle patients is not due to enzyme induction but could be due to kinetic regulation of the enzyme AMP deaminase (AMPD) which is based on hyperbolic response of enzyme activity to substrate concentration as described by the Michaelis Menten kinetics [32]. Lactate forearm ischemic test is one of the efficient diagnostic tools in different myopathies [15] and hence lacking lactate increase and excessively increased ammonia in patients with glycogenosis gives a clear hint of McArdle diseases.…”

Section: Laboratory Findingsmentioning

confidence: 99%

McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients

2020

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A clinical, biochemical, histological and molecular genetic analysis of 60 McArdle patients (33 males and 27 females; mean age at diagnosis: 37 years) was performed. The objective of this study was to identify a possible genotype-phenotype correlation in McArdle disease. All patients complained of exercise-induced myalgia and fatigue; permanent weakness was present in 47% of the patients. Five percent of patients conveyed of masticatory muscle weakness. Age of onset was <15 years in 92% patients. Serum creatine kinase was elevated 5 to13-fold. Forearm ischemic test showed decreased lactate production but excessively increased ammonia upon exercise (n = 16). Muscle biopsies revealed highly reduced or missing myophosphorylase activity (n = 20) (mean: 0.17 ± 0.35 U/g tissue; normal: 12-61) and histologically, sub-sarcolemmal glycogen accumulation (n = 9). Molecular genetic analysis revealed the common p.Arg50Ter mutation in 68% of the patients. Other rather frequent mutations were p.Arg270Ter (allele frequency: 5%) followed by c.2262delA and p.Met1Val (allele frequencies: 3%). Twenty-four other rare mutations were also identified. No genotype-phenotype correlation was observed. The analysis highlights that testing of the p.Arg50Ter mutation could be performed first in molecular genetic testing of patients with exercise intolerance possibly due to McArdle disease. However, there is enormous mutation heterogeneity in McArdle disease thus sequencing of the myophosphorylase gene is needed in patients highly suspicious of McArdle disease.

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“…In glycogen storage disease type V there is no or only attenuated lactate elevation in response to testing, while ammonia production is increased [25]. The nonischaemic forearm exercise test has been found to be less specific and sensitive and is therefore not recommended [26]. …”

Section: General Diagnostic Tools In Metabolic Myopathiesmentioning

confidence: 99%

Inborn Errors of Energy Metabolism Associated with Myopathies

Das

Steuerwald

Illsinger

2010

Journal of Biomedicine and Biotechnology

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Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed.

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Lactate production upon short-term non–ischemic forearm exercise in mitochondrial disorders and other myopathies

Abstract: The specific lactate production during NIFET is neither sufficiently specific nor sensitive for the diagnosis of mitochondrial disorders. Increased specific lactate production during rest-to-work transition period might be caused by increased acetyl group deficits.

Cited by 13 publications

References 18 publications

Metabolic Myopathies

Metabolic Myopathies

McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients

Inborn Errors of Energy Metabolism Associated with Myopathies

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