The majority of mitochondrial disorders do not fit well within any characterized syndrome. Some of the better characterized mitochondrial disorders are:
Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)
MELAS is a progressive disease that usually begins in childhood or adolescence. It affects many body systems and progresses with age. Early symptoms include muscle weakness, headaches, seizures and recurrent vomiting. Lactic acidosis can cause vomiting, fatigue, muscle weakness and pain. Most patients with MELAS will have a stroke-like episode by age 40. Stroke-like episodes can involve seizures, loss of vision, temporary muscle weakness and severe headaches. Over time, many stroke-like episodes can cause brain damage and impair cognitive function. Other symptoms can include ataxia, heart disease and diabetes.
Myoclonic Epilepsy and Ragged-Red Fibers (MERRF)
MERRF is a progressive disease that affects multiple systems of the body. In most cases, signs of MERRF appear during childhood or adolescence. Most patients with MERRF have myoclonus. Epileptic seizures, ataxia and peripheral neuropathy are common features. Hearing loss and heart abnormalities sometimes occur. When muscle cells from an affected individual are stained and examined under a microscope, they appear as “ragged-red fibers.”
Leber’s Hereditary Optic Neuropathy (LHON)
LHON usually affects people in their early 20s, and it is in more common in males than females. LHON causes sudden, painless loss of central vision in both eyes. In most cases, vision loss is permanent, although some people will have gradual improvement in their vision over time. LHON is often caused by homoplasmic mutations in electron transport chain complex I genes and is inherited in a maternal pattern.
Leigh syndrome is characterized by progressive degeneration of the lower brainstem. Children with this condition develop respiratory abnormalities around 1 to 2 years of age. They may also have ophthalmoplegia, ataxia, peripheral neuropathy, hypotonia and psychomotor regression.
Barth syndrome is a mitochondrial condition that follows X-linked inheritance and primarily affects boys. Symptoms may include dilated cardiomyopathy, skeletal myopathy, short stature, and recurrent infections due to neutropenia.
Chronic Progressive External Ophthalmoplegia (CPEO)
CPEO is characterized by weakness of the muscles that move the eye. The first signs of this condition often begin in early adulthood and may include ptosis, ophthalmoplegia, myopathy of the arms and legs, and dysphagia. Other symptoms can include hearing loss and ataxia.
Kearns-Sayre Syndrome (KSS)
Individuals with Kearns-Sayre syndrome have chronic external ophthalmoplegia and pigmentary retinopathy, which can cause loss of vision. Other symptoms of KSS can include cardiac conduction defects, ataxia, elevated protein levels in cerebral spinal fluid, hearing loss, kidney disease, diabetes or slow growth. Some patients with KSS develop dementia. KSS usually affects people under the age of 20.
Mitochondrial Associated Hearing Loss
Patients with this 1555A>G mutation in the 12S rRNA gene can develop pre-lingual or post-lingual hearing loss. If infants with this genotype are treated with aminoglycoside antibiotics, hearing loss develops early in life. Individuals without aminoglycoside exposure may develop hearing loss in adulthood.
Mitochondrial Depletion Syndrome
Mitochondrial depletion syndrome is caused by a drastic reduction in the amount of mtDNA in the cell. Most cases present in childhood with organ malfunction due to lactic acidosis. The presentation of mitochondrial depletion syndrome can be very different among individuals. Organs that may be affected include the muscles, heart, liver, kidneys and brain.
Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE)
MNGIE mostly affects the nervous system and digestive system. Symptoms usually begin before age 20. Gastrointestinal dysmotility prevents food from moving through the digestive tract effectively. Gastrointestinal dysmotility can result in symptoms such as feeling full easily, trouble swallowing, nausea and intestinal blockage. Leukoencephalopathy is a hallmark of this condition. Other features of MNGIE can include numbness and weakness of the limbs, weakness of eye muscles and hearing loss.
Neurogenic Muscle Weakness, Ataxia and Retinitis Pigmentosa (NARP)
Patients with this condition may have numbness or tingling in the extremities, muscle weakness, balance problems, hearing loss and vision loss caused by retinitis pigmentosa. Developmental delay and learning disabilities are also seen.
Pearson syndrome is a condition that presents in early childhood. The main features of Pearson syndrome are bone marrow dysfunction and pancreatic insufficiency. Muscle weakness and neurological impairment also may occur. Pearson syndrome is usually fatal, but those who survive often develop symptoms of Kearns-Sayre syndrome.
Pyruvate Carboxylase Deficiency
Symptoms of pyruvate carboxylase deficiency include seizures, lactic acidosis, low blood sugar, failure to thrive, growth retardation and developmental delay.
Pyruvate Dehydrogenase Deficiency
Patients with pyruvate dehydrogenase deficiency have different symptoms depending on disease onset. Early onset disease results in lactic acidosis (buildup of lactic acid in the body) and brain and kidney abnormalities. Later onset forms result in balance and coordination problems when walking and cognitive decline. Growth delay, low muscle tone, tingling in the extremities and other birth defects can also occur.
POLG1 encodes gamma polymerase for mtDNA synthesis. There are six major clinical disorders which can be caused by mutations in POLG1: Alpers-Huttenlocher syndrome (AHS); childhood myocerebrohepatopathy spectrum (MCHS); myoclonic epilepsy, myopathy and sensory ataxia (MEMSA); ataxia neuropathy spectrum (ANS); autosomal recessive progressive external ophthalmoplegia (arPEO); and autosomal dominant progressive external ophthalmoplegia (adPEO). Mutations in POLG1 have also been associated with MNGIE-like syndrome, MELAS, Parkinson's disease and premature menopause. Individuals with POLG1 mutations are also at significant risk of drug-induced liver failure.