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

• Combined Oxidative Phosphorylation Deficiency Disease
• COXPD Disorder

What is Combined Oxidative Phosphorylation Deficiency Disorder? (Definition/Background Information)

• Combined Oxidative Phosphorylation Deficiency (COXPD) Disorder is a disease that affects many parts of the body
• There are many subtypes, caused by many different gene mutations. It is inherited in an autosomal recessive pattern
• Onset occurs at or soon after birth in most cases, and features can include growth retardation, small head (microcephaly), increased muscle tone, floppiness of the trunk and head, brain disease (encephalopathy), enlarged heart muscle (cardiomyopathy), and liver dysfunction
• The treatment for Combined Oxidative Phosphorylation Deficiency Disorder is supportive

(Source: Combined Oxidative Phosphorylation Deficiency; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Combined Oxidative Phosphorylation Deficiency Disorder? (Age and Sex Distribution)

• Combined Oxidative Phosphorylation Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Combined Oxidative Phosphorylation Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Combined Oxidative Phosphorylation Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for COXPD Disorder

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 Combined Oxidative Phosphorylation Deficiency Disorder? (Etiology)

• Combined Oxidative Phosphorylation Deficiency Disorder is caused by mutation(s) in different genes, leading to different subtypes of the disorder. Thus,
  • COXPD1 is caused by mutations in the GFM1 gene
  • COXPD11 is caused by mutations in the RMND1 gene
  • COXPD14 results from mutations in the FARS2 gene
  • COXPD15 is caused by mutations in the MTFMT gene
  • COXPD16 is caused by MRPL44 gene mutations
• COXPD Disorder is inherited in an autosomal recessive manner

Autosomal recessive pattern of 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).

What are the Signs and Symptoms of Combined Oxidative Phosphorylation Deficiency Disorder?

The signs and symptoms of Combined Oxidative Phosphorylation Deficiency Disorder may vary, depending on the specific type of disorder an individual is afflicted with. The following are some signs and symptoms of COXPD Disorder:

• Developmental delay
• Muscle stiffness
• Floppiness of head and trunk
• Abnormalities in the liver
• Enlarged heart
• Small head (microcephaly)
• Encephalopathy

How is Combined Oxidative Phosphorylation Deficiency Disorder Diagnosed?

Combined Oxidative Phosphorylation Deficiency Disorder 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
• Molecular genetic testing for known gene mutations that cause specific COXPD Disorder types

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 Combined Oxidative Phosphorylation Deficiency Disorder?

The complications of Combined Oxidative Phosphorylation Deficiency Disorder may include:

• Liver dysfunction
• Heart failure
• Paralysis
• Coma

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

How is Combined Oxidative Phosphorylation Deficiency Disorder Treated?

There is no cure for Combined Oxidative Phosphorylation Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Combined Oxidative Phosphorylation Deficiency Disorder be Prevented?

Combined Oxidative Phosphorylation Deficiency Disorder 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), if available, 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 Combined Oxidative Phosphorylation Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Combined Oxidative Phosphorylation Deficiency Disorder 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 Combined Oxidative Phosphorylation Deficiency Disorder:

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

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