Mitochondrial Myopathy and/or Encephalomyopathy

Examples include:

Barth syndrome

• Onset: Present at birth (symptoms apparent at childhood)
• Symptoms: weakened heart muscle  (cardiomyopathy),  arrhythmias , heart failure, low white blood cells (neutropenia), and underdeveloped skeletal muscle which leads to weakness and growth delays. Distinct facial features, including prominent ears, cheekbones, and deep-set eyes.
• Almost always exclusively diagnosed in male infants.

Cytochrome C Oxidase deficiency

• Age: Birth onwards
• Symptoms: high levels of lactic acid in the blood (lactic acidosis), muscle weakness and kidney problems , excessive thirst and dehydration.

Kearns-Sayre syndrome

• Onset: Before age 20
• Symptoms: This disorder is defined by PEO and pigmentary retinopathy, a “salt-and-pepper” pigmentation in the retina that can affect vision, but often leaves it intact. Other common symptoms include conduction block (in the heart) and ataxia. Less typical symptoms are mental retardation or deterioration, delayed sexual maturation and short stature.

Leigh syndrome and maternally inherited Leigh syndrome

• Onset: Infancy
• Symptoms: Leigh syndrome causes brain abnormalities that can result in ataxia, seizures, impaired vision and hearing, developmental delays and altered control over breathing. It also causes muscle weakness, with prominent effects on swallowing, speech and eye movements.

Mitochondrial DNA depletion syndrome

• Onset: Infancy
• Symptoms: This disorder typically causes muscle weakness and/or liver failure, and more rarely, brain abnormalities. “Floppiness,” feeding difficulties and developmental delays are common symptoms; PEO and seizures are less common.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

• Onset: Childhood to early adulthood
• Symptoms: MELAS causes recurrent stroke like episodes in the brain, migraine-type headaches, vomiting and seizures, and can lead to permanent brain damage. Other common symptoms include PEO, general muscle weakness, exercise intolerance, hearing loss, diabetes and short stature.

Mitochondrial neurogastrointestinal encephalomyopathy

• Onset: Usually before age 20
• Symptoms: This disorder causes PEO, ptosis (droopy eyelids), limb weakness and gastrointestinal (digestive) problems, including chronic (long term) diarrhoea and abdominal pain. Another common symptom is peripheral neuropathy (a malfunction of the nerves that can lead to sensory impairment and muscle weakness).

Myoclonus epilepsy with ragged red fibers (MERRF)

• Onset: Late childhood to adolescence
• Symptoms: The most prominent symptoms are myoclonus (muscle jerks), seizures, ataxia and muscle weakness. The disease also can cause hearing impairment and short stature.

Neuropathy, ataxia and retinitis pigmentosa (NARP)

• Onset: Infancy to adulthood
• Symptoms: NARP causes neuropathy (a malfunction of the nerves that can lead to sensory impairment and muscle weakness), ataxia and retinitis pigmentosa (degeneration of the retina in the eye, with resulting loss of vision). It also can cause developmental delay, seizures and dementia.

Pearson syndrome

• Onset: Infancy
• Symptoms: This syndrome causes severe anaemia and malfunction of the pancreas. Children who survive the disease usually go on to develop Kearns-Sayre syndrome.

Progressive external ophthalmoplegia (PEO)

• Onset: Usually in adolescence or early adulthood
• Symptoms: PEO — the gradual paralysis of eye movements — is often a symptom of mitochondrial disease, but sometimes it stands out as a distinct syndrome. It’s frequently associated with exercise intolerance.

www.mda.org

Thymidine kinase 2 deficiency

Infantile-Onset:

• Typically begin before one year of age, early development and growth are normal.
•  Symptoms include: low muscle tone (hypotonia) and muscle weakness of the arms and legs. Other early signs include feeding problems and difficulty breathing.
• Some patients with infantile-onset TK2D also have a brain disease known as encephalopathy. This can lead to developmental and cognitive problems, hearing loss and seizures.

Childhood-Onset

• Symptoms of childhood-onset TK2D appear between the ages of 1 and 12 years.
• The first signs are typically muscle weakness of the arms and legs.
• The facial muscles are also often involved leading to facial paralysis and droopy eyelids (ptosis).
• The muscles of the eyeballs may also be affected, leading to difficulties in moving the eyeballs (progressive external ophthalmoparesis or PEO).

Late-Onset

• Symptoms of the late-onset type of TK2D begin after age 12.
• The muscles of the limbs become weak, particularly shoulders, arms, hips and thighs (proximal muscle weakness).
• One of the first symptoms may be weakness of the shoulder muscles causing the shoulder blade to stick out (scapular winging).
• Facial muscle weakness can cause droopy eyelids (ptosis) and weakness of the muscles that move the eye (progressive external ophthalmoplegia or PEO). Other symptoms include difficulty swallowing and talking.

NORD