Mitochondrial disease is a complex group of conditions in which the cell mitochondria have reduced function in due to genetic mutations. Mitochondrial diseases are considered among the most common hereditary metabolic (metabolic-related) diseases. The mitochondria are "the cell's power plant" and disease here can cause impaired function especially in the muscles, central nervous system (the brain) and other organs in different combinations, depending on the disease subgroup (different genetic defects, see below). The mitochondria are probably important also in the development of diseases that initially have other causes, such as Systemic connective tissue diseases:, Vasculitis and other Autoimmune conditions (reference: White ME, 2010). Often, the disease starts early in adolescence, but some forms begin in adulthood. Mitochondrial disease can cause signs of unusually severe muscle damage (rhabdomyolysis) after physical exercise.
Genetic mutations (Change in heredity) is present. These may be congenital or acquired. Infections and medications can probably cause the mutations.
It is estimated that 1: 10.000 children in Sweden develop mitochondrial disease before school age (reference: Darin N, 2001).
- Low body height
- Muscle Disease (Without Other Symptoms)
- Stroke, cramps, ataxia, dementia
- Combined brain (CNS) and muscle disease from childhood
- Multi-organ disease with muscular disease
- Eye: Vision with pigmented retinopathy, optic atrophy, cataracts
- Diabetes mellitus (pancreas) and hypo-parathyroidism
- Kidney: Progressive renal failure
- Skin: Multiple lipomes (many fat knots)
Symptoms and severity vary between the different forms and from person to person. Loss of muscle strength, disturbed vision, hearing, heart, lung, liver, kidney and / or bowel function occurs. Some get learning difficulties and serious neurological and / or mental symptoms.
Isolated muscle disease occurs. Typically, reduced tolerance for exercise and exercise is then achieved. Fatigue, muscle weakness, muscle pain and subsequent increase in the enzyme CK (creatine kinase) in blood samples.
Suspicion of the disease should be aroused when clear symptoms of the brain (CNS), peripheral nerves, endocrinological, heart, eyes, intestines, skin and bone marrow are present. Reduced exercise tolerance and elevated blood creatine kinase (CK) are common.
- Clinical disease picture and medical history (debut age, manifestations)
- Heritage: Some cases: Women may be "carriers" and boys / men get symptoms. Check medical history over three generations
- Blood samples (count of blood cells, CK, LD, creatinine, blood sugar, uric acid, albumin, alanine (amino acid), acyl carnitine
- Spinal fluid in brain (CNS) symptoms: lactate, pyruvate, amino acids, 5-methyltetrahydrofolate
- EMG (Electro-myography)
- MRI if symptoms from the brain
- Eyelid examination
- Muscle tests during / after exercise
- Genetic tests for (when possible) detecting genetic mutation
- Sequencing of mitochondrial DNA
- Testing of diseased tissue (biopsy)
- Biopsy (tissue sample), most often from thigh muscle (vastus lateralis musculus)
- «Ragged Fiber»
- Histochemical investigations
- Electron microscopy
- Diabetes mellitus with deafness (DAD)
- The condition may also have other causes
- Leber`s hereditary optic neuropathyi (LHON)
- Visual loss that begins in early adulthood, most often among men
- Leigh syndrome, Subacute sclerosing encephalopathy
- Beginning most often at the end of the first year of life, but disease start is also seen among adults
- Neuropathy, ataxia, retinitis pigmentosa and ptosis (NARP)
- Mitochondrial myopathy
- Myo-neurogenic gastrointestinal encephalopathy (MNGIE)
- Gastrointestinal pseudo obstruction
- Myoclonic Epilepsy with Ragged Red Fibers»(MERRF)
- "Ragged Red Fibers" are clumsy, diseased mitochondria in tissue sample (biopsy)
- Low body height, hearing loss, lactate acidosis, intolerance to physical exercise
- Mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptoms (MELAS)
Incorrect diagnosis (Similar conditions, differential diagnoses)
- Creatine kinase (CK) is usually higher and ANA (with subgroups) are present in blood sample, MRI, EMG, biopsy
- Muscular Dystrophy
- CK in blood test, EMG, Biopsy
- Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS) and other neurological, progressive diseases
- Antiphospholipid syndrome and other conditions that can cause strokes
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 evidence of the effect on such vitamin / dietary supplements is not clear.