Mitochondrial Diseases are a heterogeneous group of clinical syndromes sharing a common energy deficiency due to faulty mitochondrial OXPHOS metabolism. Mitochondria are involved in numerous metabolic pathways, but the definition of mitochondrial disease is restricted to syndromes resulting from OXPHOS deficiency.

Since mitochondria are present in all tissues, mitochondrial disease can affect any organ of the body. However, those most vulnerable are the skeletal muscle, the brain and, less frequently, the heart. For this reason diseases are also referred to as Mitochondrial Encephalo-myopathies or Encephalo-cardio-myopathies, but of course other tissues and organs may also be affected. Organ failure is more frequent during the first two decades of life, because of the greater need for energy during development and growth. However, later-onset syndromes are also well known.

On the clinical level, mitochondrial disease can vary greatly in regards to age of onset, type of evolution, and tissues involved.

In newborns, for example, disease can present a serious anemia and malfunction of the pancreas (Pearson's Syndrome),or severe hypertrophic cardiomyopathy and decrease of circulating white blood cells (Barth's Syndrome). Other possible presentations include the "Floppy Infant syndrome", due to severe infantile myopathies, or severe, early-onset liver failure leading to keto-acidosis and coma caused by mtDNA depletions.

In childhood clinical manifestations can include either development arrest or delay, recurrent myoglobnuria, renal insufficiency (especially proximal tubular acidosis with loss of aminoacids in the urine), endocrine malfunctions such as diabetes mellitus, diabetes insipidus, retinitis pigmentosa, optic atrophy and deafness, or a progressive encephalopathy with or without convulsions.

In adults, the most frequent symptoms are exercise intolerance and weakness, reflecting the prevalent involvement of skeletal muscle.

As a matter of fact, the most diverse syndromes have been described in mitochondrial pathology, from isolated deafness to multisystem syndromes involving different organs and apparatuses.

When is to suspect a mitochondrial disease?
As we have emphasized above, mitochondrial diseases are clinically variable and therefore difficult to diagnose. It is often necessary to seek for the collaboration of specialists in different fields: neurology, pediatrics, cardiology, biochemistry, and genetics. A mitochondrial pathology is usually suspected in patients who present an association of different symptoms, involving different organs but hallmarked by a progressive neuromuscular insufficiency.

Typical morphological abnormalities found in muscle biopsy of patients affected by mitochondrial myopathy.

Morbidic map of mtDNA.

Problems associated with mitochondrial disease
Involved Organs Possible correlated problems

Psychomotor delay, dementia, epilepsy, psychiatric problems, migraine, stroke-like episodes.

Peripheral nervous system

Localized pain, deep reflexes absent, gastrointestinal disturbances (gastro-esophageal reflux, slow gastrointestinal movements, pseudo-obstruction), faintness and syncopal episodes, abnormalities of sweating, urinary bladder control and defecation.


Hypotonia, muscle weakness with or without muscle wasting, exercise intolerance, cramps and myoglobinuria.


Proximal tubular insufficiency (loss of proteins, magnesium, phosphorus, calcium, sodium, potassium and other important ions


Conduction defects, cardiomyopathy.


Hypoglycemia, liver failure.


Visual loss, narrowing or other abnormalities of visual field.

Auditory apparatus

Syndromic or non-syndromic, usually post-lingual, sensorineural hearing loss.


Diabetes mellitus or insufficiency of exocrine pancreas leading to malabsorption.


Failure to thrive, poor growth,short stature.