A Diagnostic Algorithm for Metabolic Myopathies

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A Diagnostic Algorithm for Metabolic Myopathies

Postby dlf » Sat 29 Aug 2015 14:27

Exercise intolerance, myalgias, fatigue??? Something to consider........

Full text with diagnostic algorithm at:


Curr Neurol Neurosci Rep. 2010 Mar; 10(2): 118–126.
doi: 10.1007/s11910-010-0096-4
PMCID: PMC2872126
A Diagnostic Algorithm for Metabolic Myopathies
Andres Berardo, Salvatore DiMauro, and Michio Hiranocorresponding author
Department of Neurology, Columbia University Medical Center, 630 West 168th Street, P&S 4-423, New York, NY 10032, USA
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).


From a clinical point of view, metabolic myopathies can be categorized into two different groups: 1) those that show symptoms and signs related to exercise (exercise intolerance, cramps, myalgias, myoglobinuria) with normal interictal examination and 2) those with fixed symptoms, such as muscle weakness, often associated with systemic involvement (eg, endocrinopathies or encephalopathies). When evaluating a patient with exercise-related symptoms, we should ask two questions: 1) What type of exercise provokes symptoms? 2) Are there associated triggering factors? If short bursts of high-intensity exercise trigger muscle cramps or pigmenturia, the patient may have a defect of glycogen metabolism [3]. Examples of this type of activity include weight lifting and sprinting. In the United States and other countries where baseball is popular, the “home run” (Haller) sign—that is, the inability to sprint around the bases because of exercise-induced muscle spasms—is a typical complaint in young patients with glycogenoses, such as McArdle disease (Dr. Ronald Haller, personal communication). In contrast, if the patient reports that prolonged exercise (eg, hiking or playing soccer) triggers myalgias, fatigue, and pigmenturia without acute contractures, he or she likely has a defect of fatty acid oxidation. The symptoms often occur when the patient is fasting. A prototypical example is a young adult with CPT II deficiency who enlists in military service and has difficulty completing long marches because of fatigue and myalgias followed by pigmenturia. Some patients with glycolytic or lipid disorders may develop progressive myopathy and persistent weakness. Patients with mitochondrial diseases may show a wide range of manifestations that are exercise induced, fixed, or both, but exercise intolerance is particularly common and manifests as the inability to perform activities because of premature fatigue out of proportion to weakness. This article briefly goes through general clinical aspects of these metabolic myopathies, emphasizing the more common forms (Table 1), and provides an algorithm for diagnosing these diverse conditions (Fig. 1).

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Re: A Diagnostic Algorithm for Metabolic Myopathies

Postby RitaA » Sat 29 Aug 2015 18:26

Thanks for posting, dlf!

From the full article:

Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome is characterized clinically by strokes that are atypical in that they usually occur in people less than 40 years old and generally do not conform to large vessel distribution [39]. Although MELAS is a maternally inherited condition, the proband often is the only family member with the full MELAS syndrome, whereas oligosymptomatic matrilineal relatives may manifest milder signs (eg, diabetes, deafness, migraine-like headaches) and some mutation carriers are asymptomatic. The diagnosis of MELAS can be confirmed by detection of the pathogenic mtDNA point mutation in blood. About 80% of MELAS patients harbor the m.3243A>G mutation in the tRNALeu(UUR) gene [40, 41], but at least 20 additional mtDNA mutations have been reported to cause this disorder.

Since two members of my extended family in Finland had been diagnosed with MELAS, it’s one of many genetic disorders I was tested for once I started experiencing stroke-like episodes and other neurological signs and symptoms. Lucky for me, I tested negative for MELAS, and the stroke-like episodes (which were initially diagnosed as complicated migraine and/or TIA) stopped once I was treated for Lyme disease.

Unfortunately, my third cousin died last December despite receiving the best of care from one of the world’s leading MELAS experts in Tampere, Finland. I have since discovered that MELAS isn’t all that rare, and that some people who are carriers of the gene mutation may experience relatively few (and sometimes even no) symptoms. As an example, my mother's cousin experienced only hearing loss, whereas her son was dependent on a wheelchair for many years.

http://ghr.nlm.nih.gov/condition/mitoch ... e-episodes

What is MELAS?

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).

Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, and hormonal imbalances.

How common is MELAS?

The exact incidence of MELAS is unknown. It is one of the more common conditions in a group known as mitochondrial diseases. Together, mitochondrial diseases occur in about 1 in 4,000 people.

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