What are the other Names for this Condition? (Also known as/Synonyms)

• Metabolic Myopathy Associated with Chronic Lactic Acidemia, Growth Failure, and Nerve Deafness
• Mitochondrial Myopathy-Lactic Acidosis-Deafness Syndrome
• MMLA (Mitochondrial Myopathy with Lactic Acidosis)

What is Mitochondrial Myopathy with Lactic Acidosis? (Definition/Background Information)

• Mitochondrial Myopathy with Lactic Acidosis (MMLA) or Mitochondrial Myopathy-Lactic Acidosis-Deafness is a type of metabolic myopathy described only in two sisters to date, presenting during childhood
• It is characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria
• There have been no further descriptions in the literature since 1973

(Source: Mitochondrial myopathy-lactic acidosis-deafness syndrome Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Mitochondrial Myopathy with Lactic Acidosis? (Age and Sex Distribution)

• Mitochondrial Myopathy with Lactic Acidosis is an extremely rare congenital disorder. It has only been described in 2 sisters, in the medical literature
• The presentation of symptoms may occur in childhood
• Both males and females may be affected

What are the Risk Factors for Mitochondrial Myopathy with Lactic Acidosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Mitochondrial Myopathy with Lactic Acidosis can be inherited
• Currently, no other risk factors have been clearly identified for MMLA

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mitochondrial Myopathy with Lactic Acidosis? (Etiology)

• Mitochondrial Myopathy with Lactic Acidosis may be caused by compound heterozygous mutation(s) in the PNPL8 gene
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

Compound heterozygous mutations are those where each copy of a gene in all cells of an individual carries a recessive mutation, and the combination of these mutations causes the condition

What are the Signs and Symptoms of Mitochondrial Myopathy with Lactic Acidosis?

The signs and symptoms of Mitochondrial Myopathy with Lactic Acidosis may vary in type and severity among affected individuals, and include:

• Dysarthria
• Dysmetria
• Dystonia
• Episodic vomiting
• Focal seizures with impairment of consciousness or awareness
• Generalized hypotonia
• Gowers sign
• Hemiparesis
• Increased serum lactate
• Increased serum pyruvate
• Infantile onset
• Lactic acidosis
• Moderate sensorineural hearing impairment
• Muscle weakness
• Postnatal growth retardation
• Spasticity
• Toe walking

Very frequently present symptoms in 80-99% of the cases:

• EMG abnormality
• Hyperalaninemia
• Metabolic acidosis
• Mitochondrial myopathy
• Myopathy
• Sensorineural hearing impairment
• Skeletal muscle atrophy
• Vaginal fistula

Frequently present symptoms in 30-79% of the cases may include seizures.

(Source: Mitochondrial Myopathy with Lactic Acidosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Mitochondrial Myopathy with Lactic Acidosis Diagnosed?

Mitochondrial Myopathy with Lactic Acidosis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mitochondrial Myopathy with Lactic Acidosis?

The complications of Mitochondrial Myopathy with Lactic Acidosis may include:

• Problems with movement
• Severe speech impediment
• Risk of falls and injury due to seizures
• Severe fatigue

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Mitochondrial Myopathy with Lactic Acidosis Treated?

There is no cure for Mitochondrial Myopathy with Lactic Acidosis, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Mitochondrial Myopathy with Lactic Acidosis be Prevented?

Currently, Mitochondrial Myopathy with Lactic Acidosis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Mitochondrial Myopathy with Lactic Acidosis? (Outcomes/Resolutions)

• The prognosis of Mitochondrial Myopathy with Lactic Acidosis is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Mitochondrial Myopathy with Lactic Acidosis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/