Primary Mitochondrial Disease

Primary Mitochondrial Disease (PMD) is genetically inherited and diagnosed by identifying mutations on mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) that result in mitochondrial dysfunction. PMDs can occur due to germline mutations mtDNA and/or nDNA genes encoding ETC proteins. Point mutations can occur in any of the mtDNA’s 37 genes encoding 13 proteins or the 1,000 nDNA genes, which are essential for optimal ETC function. Some common primary mitochondrial diseases include:



  • Progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease

  • Affects both genders equally

  • Affects fewer than 1 in 200,000


Signs and Symptoms

  • Increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia)

  • Usually indicated by seizures at any age between 3 months and 5 years

  • Lack of coordination

  • Partial paralysis

  • Limbs appear to be stiff



  • Characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small number of white blood cells (neutropenia) and short stature

  • Occurs almost exclusively in males

  • Most often present at birth or develops in the first months of life

  • Affects 1 in 300,000 to 400,000 individuals worldwide – more than 150 cases have been described in scientific literature


Signs and Symptoms

  • May have elastic fibers in place of muscle fibers in some areas of the heart muscle

  • Skeletal myopathy is usually noticeable from birth and causes low muscle tone

  • Muscle weakness often causes delay of motor skills such as crawling and walking

  • Extreme tiredness

  • Neutropenia – low levels of white blood cells – makes it more difficult for the body to fight off foreign invaders

  • Newborns are often smaller than normal

  • Distinctive facial features

    • Prominent cheeks

  • Normal intelligence but often have difficulty performing tasks involving math or visual-spatial skills such as puzzles



  • Condition characterized mainly by a loss of the muscle functions involved in eye and eyelid movements


Signs and Symptoms

  • Tend to begin in early adulthood (18-40) and most commonly include weakness or paralysis of the muscles that move the eye and drooping of the eyelids

  • General weakness of the skeletal muscles

  • Difficulty swallowing



  • Genetic condition that affects the nervous system and causes movement problems

  • Develop impaired muscle coordination that worsens over time

  • Most people begin experiencing signs and symptoms between 5 and 15

  • Affects 1 in 40,000 people in the US.

  • This condition is found in people with European, Middle Eastern or North African ancestry. It is rarelyidentified in other ethnic groups.


Signs and Symptoms

  • Gradual loss of strength and sensation in the arms and legs, muscle stiffness (spasticity), impaired speech, hearing and vision

  • Often have a form of heart disease called hypertrophic cardiomyopathy

  • Some individuals develop diabetes or an abnormal curvature of the spine (scoliosis)

  • Poor coordination and balance

  • 25% of people have an atypical form in which signs and symptoms begin after age 25

  • Affected individuals usually require a wheelchair about 10 years after signs and symptoms appear



  • A form of metabolic acidiosis that begins in the kidneys

  • Kidneys are unable to remove excess acid from their body

  • Most forms of lactic acidosis are caused by too much L-lactate


Signs and Symptoms

  • Some symptoms represent a medical emergency: Fruity-smelling breath, confusion, jaundice, trouble breathing or shallow, rapid breathing

  • Exhaustion or extreme fatigue, muscle cramps or pain, body weakness, overall feelings of physical discomfort, diarrhea, decrease in appetite, headache, rapid heart rate



  • Rare genetic disorder of fatty acid metabolism that is transmitted as an autosomal recessive trail

  • Occurs when an enzyme needed to break down certain very long-chain fatty acids is missing or not working properly

  • Severe form – which undiagnosed can lead to extreme weakness of the heart muscles and may be life-threatening (Early-onset)

  • Milder form – repeated bouts of low blood sugar (Later-onset)

  • 1 in 40,000 babies


Signs and Symptoms

  • Early-onset symptoms are apparent within days or weeks of birth

  • Low blood sugar, irritability, listlessness

  • Thickening of the heart muscles, abnormal hearth rhythms, cardiorespiratory failure

  • Later-onset

    • Recurrent episodes of lethargy and even coma associated with low blood sugar during infancy and a noticeably enlarged liver during childhood

    • Periodic attacks of muscle pain and breakdown

  • Recurrent increased acid levels in blood and body tissues, sudden cessation of breathing and even cardiac arrest

  • Fat deposits and abnormal enlargement of the liver, poor muscle tone, cardiomyopathy




  • Sever neurological disorder that usually becomes apparent in the first year of life

  • Characterized by progressive loss of mental and movement abilities

  • Typically results in death within two or to three years

  • Affects 1 in 40,000 people

    • 1 in 2,000 in Saguenay Lac-Saint-Jean region or Quebec

    • 1 in 1,700 on the Faroe Islands

Signs and symptoms are caused in part by patches of damaged tissue that develop in the brains of people with these conditions


Signs and Symptoms

  • Vomiting, diarrhea, difficulty swallowing (dysphagia) which disrupts eating

  • These problems often result in an inability to grow or gain weight at the expected rate

  • Severe muscle and movement problems

  • Weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia)

  • Loss of sensation and weakness in the limbs (peripheral neuropathy)

  • Weakness or paralysis of the muscles that move the eyes (ophthalmoparesis), rapid involuntary eye movements (nystagmus), degermation of the nerves that carry information from the eyes to the brain

  • Severe breathing problems

  • Hypertrophic cardiomyopathy





  • An inherited form of vision loss

  • Usually begins in a person’s teens or twenties, rare cases may appear in early childhood or later adulthood

  • Males are affected much more than females

  • Prevalence in most populations is unknown. It affects 1 in 30,000 to 50,000 people in northeast England and Finland


Signs and Symptoms

  • Blurring and clouding of vision are usually the first symptoms (either in one eye or both)

  • Overtime there is a severe loss of sharpness (visual actuity) and colour vision

  • Mainly affects central vision

  • Vision is typically the only symptom, if there are additional symptoms this is considered


Signs and Symptoms

  • In addition to vision loss, symptoms include:

    • Movement disorders, tremors, abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects)



  • Characterized clinically by hypermetabolism and consequent abnormal transpiration (fast metabolism and sweat more than usual)

  • Defect in mitochondrial energy metabolism

  • Rarest form

  • Only two cases reported (1959 and 1970)


Signs and Symptoms

  • Muscle weakness

  • Excessive perspiration

  • Hypermetabolism

  • Increased fluid intake without polyuria

  • High-caloric intake without increase in body weight




  • Condition that prevents the body from converting certain fats to energy

  • 1 in 17,000 in the US.


Signs and Symptoms

  • Vomiting, lack of energy, low blood sugar

  • At risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, sudden death

  • Can be triggered by periods of fasting or illnesses







  • Affects many of the body’s systems, particularly the brain and nervous system and muscles

  • Most people with MELAS have a buildup of lactic acid in their body

  • One of the more common conditions in a group known as mitochondrial diseases


Signs and Symptoms

  • Most often appear in childhood following a period of normal development

  • Early symptoms: muscle weakness and pain, recurrent headaches, loss of appetite, vomiting and seizures

  • Most affected individuals experience stroke-like episodes before 40 – temporary muscle weakness on one side of the body, altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines

  • Involuntary muscle spasms, impaired muscle coordination, hearing loss, heart and kidney problems, diabetes, and hormonal imbalances




  • Affects many parts of the body, particularly the muscles and nervous system


Signs and Symptoms

  • Most often appear during childhood or adolescence

  • Muscle twitches, weakness and progressive stiffness

  • Recurrent seqizures, difficulty coordinating movements, a loss of sensation in the extremities, slow deterioration of intellectual function

  • Hearing loss or optic atrophy – the degeneration of nerve cells that carry visual information from the eyes to the brain

  • Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy

  • Muscle cells usually appear abnormal (under a microscope)





  • Condition that affects several parts of the body, particularly the digestive system and nervous system

  • Major features can appear anytime from infancy to adulthood – most often begin by age 20

  • Medical problems associated with this disorder worsen over time

  • About 70 people with this disease have been reported


Signs and Symptoms

  • Abnormalities of the digestive system are among the most common and severe features

  • Almost all affected people have a condition known as gastrointestinal dysmotility – in which muscles and nerves of the digestive system do not move food through the digestive tract efficiently

    • The resulting problems include feelings of fullness after eating only a small amount (satiety), trouble swallowing (dysphagia), nausea and vomiting after eating, episodes of abdominal pain, diarrhea, and intestinal blockage

    • These problems can lead to extreme weight loss and reduced muscle mass (cachexia)

  • Abnormalities of the nervous system (milder than gastrointestinal problems)

  • Affected individuals experience tingling, numbness, and weakness in their limbs (peripheral neuropathy), particularly in the hands and feet.

    • Droopy eyelids (ptosis), weakness of the muscles that control the eye movement (ophthalmoplegia), and hearing loss

    • Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter is a hallmark of MNGIE disease




  • Variety of signs and symptoms affect the nervous system

  • Retinitis pigmentosa: causes the light-sensing cells of the retina to gradually deteriorate


Signs and Symptoms

  • Beginning in childhoold or early adulthood

  • Numbness, pain in the arms and legs, muscle weakness, problems with balance and coordination

  • Vision loss caused by changes in the light-sensitive tissue that lines the back of the eye

  • Learning disabilities and developmental delays

  • Loss of intellectual function (dementia)

  • Seizures, hearing loss, abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects)




  • Usually begins in infancy

  • Causes problems with the development of blood-forming (hematopoietic) cells in the bone marrow that have the potential to develop into different types of blood cells

  • Considered a bone marrow failure disorder

  • Function of the pancreas and other organs can be affected

  • About half of children die in infancy or early childhood due to severe lactic acidosis or liver failure

  • Many of those survive develop signs and symptoms of a related disorder called Kearns-Sayre syndrome


Signs and Symptoms

  • Pale skin, weakness, fatigue

  • Frequent infections, easy bruising and bleeding

  • Pancreas does not work as well as usual – leads to high levels of fats in the liver

  • Diabetes

  • Reduced ability to absorb nutrients from the diet

  • Inability to grow and gain weight at the expected rate

  • Build-up of lactic acid




  • A condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting)

  • Sometimes mistaken for Reye syndrome

  • Affects approximately 1 in 35,000 to 50,000 newborns


Signs and Symptoms

  • Vomiting, low blood sugar (hypoglycemia), a lack of energy, poor feeding, and a failure to gain weight and grow at the expected rate

  • Poor muscle tone, seizures, developmental delay, small head size

  • May be triggered by fasting or illness