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

• Infantile Hypertrophic Cardiomyopathy due to MRPL44 Deficiency
• Combined Oxidative Phosphorylation Defect Type 16 Disorder
• COXPD16 Disorder

What is Combined Oxidative Phosphorylation Deficiency 16 Disorder? (Definition/Background Information)

• Combined Oxidative Phosphorylation Deficiency 16 (COXPD16) Disorder, also known as Infantile Hypertrophic Cardiomyopathy, is characterized by decreased levels of mitochondrial complexes
• It is caused by mutations in the MRPL44 gene, which results in mitochondrial dysfunction. The cases described seem to be inherited in an autosomal recessive pattern
• The symptoms and signs described include an enlarged heart muscle (hypertrophic cardiomyopathy) and fatty liver (hepatic steatosis), as well as eye problems, headache, paralysis of one side of the body, Leigh-like lesions on brain magnetic resonance imaging (MRI), kidney insufficiency and neurological disease
• The treatment for Combined Oxidative Phosphorylation Deficiency 16 Disorder is supportive

(Source: Combined Oxidative Phosphorylation Deficiency 16; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Combined Oxidative Phosphorylation Deficiency 16 Disorder? (Age and Sex Distribution)

• Combined Oxidative Phosphorylation Deficiency 16 Disorder is a rare congenital disorder. The presentation of symptoms may occur in infancy
• 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 16 Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Combined Oxidative Phosphorylation Deficiency 16 Disorder can be inherited
• Currently, no other risk factors have been clearly identified for COXPD16 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 16 Disorder? (Etiology)

• Combined Oxidative Phosphorylation Deficiency 16 Disorder is caused by mutation(s) in the MRPL44 gene
• This gene codes for the mitochondrial ribosomal protein L44, which is essential for proper functioning of the mitochondria
• MRPL44 gene mutations are 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).

What are the Signs and Symptoms of Combined Oxidative Phosphorylation Deficiency 16 Disorder?

The signs and symptoms of Combined Oxidative Phosphorylation Deficiency 16 Disorder may include the following:

• Elevated hepatic transaminases
• Hypertrophic cardiomyopathy
• Increased serum lactate
• Microvesicular hepatic steatosis
• Eye problems
• Headaches
• Paralysis of one side of the body
• Leigh-like lesions on brain magnetic resonance imaging (MRI)
• Kidney insufficiency 
• Neurological disease

(Source: Combined Oxidative Phosphorylation Deficiency 16; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Combined Oxidative Phosphorylation Deficiency 16 Disorder Diagnosed?

Combined Oxidative Phosphorylation Deficiency 16 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, such as magnetic resonance imaging (MRI)
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm MRPL44 gene mutations

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 16 Disorder?

The complications of Combined Oxidative Phosphorylation Deficiency 16 Disorder may include:

• Kidney failure
• Cardiac failure

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

How is Combined Oxidative Phosphorylation Deficiency 16 Disorder Treated?

• There is no cure for Combined Oxidative Phosphorylation Deficiency 16 Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops
• Beta blockers, such as atenolol, may be prescribed to reduce the risk of death following a cardiac failure

How can Combined Oxidative Phosphorylation Deficiency 16 Disorder be Prevented?

Combined Oxidative Phosphorylation Deficiency 16 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) 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 16 Disorder? (Outcomes/Resolutions)

• The prognosis of Combined Oxidative Phosphorylation Deficiency 16 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 16 Disorder:

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

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