Mitochondrial disease and Rheumatic symptoms, CPEO, KSS, MELAS, MERRF, Q10 deficiency 4.56/5 (9)

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Mitochondrial disease is a complex group of conditions in which the cells' mitochondria ("the cell's power plant") has reduced function. Disease in the mitochondria can therefore lead to reduced strength in muscles, but also go beyond CNS (the brain) and other organs. There are several different types of mitochondrial diseases. Primary mitochondrial myopathy (muscle disease) is mentioned here in particular. Mitochondrial function is probably also important in the development of diseases that initially have other causes, such as some nerve diseases, neuromuscular diseases such as Duchenne muscular dystrophy og inclusion body myositis, Systemic connective tissue diseases:, Vasculitis and other Autoimmune conditions (reference: White ME, 2010; Russell J, 2016). In contrast to these, primary mitochondrial myopathy often starts early in childhood, but some forms are only detected in adulthood. A characteristic of mild disease is that one develops unusually severe muscle damage (rhabdomyolysis) after moderate physical exercise (reference; Nance JR, 2015). Mitochondrial myopathy is investigated and treated by paediatricians and endocrinologists. The rheumatologist's role is particularly to contribute to the investigation in order to distinguish the condition from Myositis, Dermatomyositis, Juvenile dermatomyositis, similar rheumatic inflammations and rhabdomyolysis.

Cell. 9 = mitochondrion

Disease Cause

Genetic mutations (change in heritage facilities) exists. These can be congenital or acquired. Infections and drugs can probably cause the mutations. The consequence is reduced oxidative phosphorylation (OXPHOS) in the mitochondria and lack of energy production in the form of adenosine triphosphate (ATP), particularly in skeletal muscles (reference: Ahmed ST, 2018).


It is estimated that 1:10.000 children in Sweden develop mitochondrial disease before school age (reference: Darin N, 2001).


General symptoms. Symptoms of mitochondrial disease can be very difficult to recognize at an early stage. Muscle pain, shortness of breath, exhaustion, tiredness after exercise are not necessarily associated with illness.

Eye muscles and muscle cramps. More typical signs of the disease are convulsions, weakness in the eye muscles which causes drooping eyelids (ptosis), double vision or combinations of these as in CPEO og Kearns-Sayre syndrome.

Muscle weakness, reduced development and nerve symptoms. Some cases manifest in early childhood with conspicuously flaccid musculature ("floppy infant"), reduced nutrient absorption, eventually delayed development, growth retardation and signs of severe nerve disease with episodes of paralysis, jerky movements (ataxia) and reduced vision and hearing. In some cases, the heart muscle and breathing muscles are also attacked. Such multi-organ manifestations are most common when the disease starts in childhood, while in adults the disease is to a greater extent limited to one organ (reference: the Barcelos IP, 2020).

Mitochondrial diseases with muscle manifestations (not a complete list)

  • Chronic progressive external ophthalmoplegia (CPEO) which accounts for 2/3 of cases
    • Increasing paralysis of eye muscles on both eyes (symmetrical) with double vision and drooping eyelids (ptosis), swallowing. and speech difficulties, as well as increasing weakness in the neck, shoulder and hip muscles are typical.
  • Kearns-Sayre syndrome (KSS)
    • The triad of pigmented retinopathy (eye disease), CPEO with ptosis and heart rhythm disturbances is characteristic. Weakness in muscles (shoulders, neck, hips) varies. The disease begins before the age of 20.
  • Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS)
    • The brain is attacked, so that headaches, convulsions and stroke-like episodes occur before the age of 40. Later increasing disease with hearing loss, gastrointestinal symptoms and dementia.
  • Myoclonic epilepsy with ragged red fibers (MERRF)
    • Infants with muscle spasms, later epilepsy and irregular movements (ataxia), weakness and dementia.
  • Primary coenzyme Q10 (CoQ10) deficiency
    • Several possible courses. The brain is attacked, so that convulsions, irregular movements (ataxia) and tight muscles (spasticity) occur. Kidney disease in the form of nephrotic syndrome that does not respond to steroid treatment. Muscular weakness and intolerance to exercise.
  • Isolated mitochondrial complex III deficiency
    • sporadic muscle disease with reduced tolerance for exercise, with or without myoglobin excretion in the urine.
  • TK2 deficiency / Mitochondrial DNA loss Syndrome 2
    • Three main forms: 1) infant onset with muscle failure and early death due to failure of breathing muscles. 2) Start in childhood between 1 and 12 years of age with weakness in the shoulders, neck and hips, but also increasing breathing difficulties. 3) Start after 12 years of age with swallowing and speech difficulties and general muscle weakness.


Abnormalities on skeletal muscle biopsy in mitochondrial myopathy. Serial sections through vastus lateralis in a patient with mitochondrial myopathy showing: (A) haematoxylin and eosin, (B) cytochrome c oxidase histochemistry (COX) (note the COX deficient fibers), (C) succinate dehydrogenase histochemistry (SDH) (note the sub-sarcolemmal accumulation of mitochondria analogous to a ragged red fiber), and (D) sequential COX-SDH histochemistry showing a mosaic COX defect seen in patients with mtDNA disorders.
Mitochondrial myopathy. Pfeffer G, 2011. CC BY NC 3.0

Medical history charts the time of first relevant symptoms (see above) and the development thereafter. Heredity: Some cases: Women can be "carriers" and boys/men get symptoms. Check medical history over three generations

Clinical examination aims to assess the strength and size of the muscles, but also rule out joint inflammation (arthritis), as well as assess the skin, nervous system and internal organs.

Eyelid examination to assess eye muscles and retinas.

Physical therapist: Muscle tests during and after training

Laboratory tests rarely shows special findings apart from increased creatine kinase (CK) in some, but is taken to rule out similar conditions. Inflammation tests (lowering reaction, CRP), cell counts (hemoglobin, white blood cells with differential count, platelets), liver, kidney and metabolic function tests, creatine kinase (CK), lactate, blood sugar, uric acid, albumin, alanine (amino acid), acyl- carnitinANA, anti-DNA and myositis-specific antibody. Urine sting. Genetic tests can be done in urine

Saliva and mucus from the inside of the cheek can be taken via sponge for genetic examinations. Sequencing of mitochondrial DNA.

Imaging may include MRI of muscles, most often thigh muscles and CT of lungs. MRI of the brain, MR spectroscopy

Spinal Fluid in brain (CNS) symptoms: lactate, pyruvate, amino acids, 5-methyltetrahydrofolate.

ECG to assess heart rhythm

Tissue sample (biopsy) from musculature, most often the thigh muscle is often necessary. Electron microscopy. One sees 1) "ragged-red fibers (RRF)", 2) Increased number of mitochondria is seen when staining the tissue with succinate dehydrogenase (SDH or complex II), often described as "ragged-blue fibres", 3) cytochrome c oxidase (COX or complex IV) deficiency or absence, 4) ultrastructurally abnormal mitochondria, often with paracrystalline inclusions. Gene tests in muscle can be performed. (reference: the Barcelos IP, 2020).

Similar conditions, differential diagnoses


Symptoms (muscle pain, cramps, diabetes, heart failure, hearing loss) are important. Custom physical exercise / exercises may be useful. Combination of high doses coenzyme Q10, in combination with creatine and L-carnitine can be tried, but documentation of the effect on such vitamin/dietary supplements is not clear. Newer drugs are elemipretide for myopathy in general and deoxycytidine (dC) + deoxythymidine (dT) against TK2 stomach. Gene therapy is promising for the future (reference; the Barcelos IP, 2020)


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