Primary coenzyme Q10 deficiency is a disorder that can affect many parts of the body, especially the brain, muscles, and kidneys. As its name suggests, the disorder involves a shortage (deficiency) of a substance called coenzyme Q10.

The severity, combination of signs and symptoms, and age of onset of primary coenzyme Q10 deficiency vary widely. In the most severe cases, the condition becomes apparent in infancy and causes severe brain dysfunction combined with muscle weakness (encephalomyopathy) and the failure of other body systems. These problems can be life-threatening. The mildest cases of primary coenzyme Q10 deficiency can begin as late as a person's sixties and often cause cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Other neurological abnormalities that can occur in primary coenzyme Q10 deficiency include seizures, intellectual disability, poor muscle tone (hypotonia), involuntary muscle contractions (dystonia), progressive muscle stiffness (spasticity), abnormal eye movements (nystagmus), vision loss caused by degeneration (atrophy) of the optic nerves or breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and sensorineural hearing loss (which is caused by abnormalities in the inner ear). The neurological problems gradually get worse unless treated with coenzyme Q10 supplementation.

A type of kidney dysfunction called nephrotic syndrome is another common feature of primary coenzyme Q10 deficiency. It can occur with or without neurological abnormalities. Nephrotic syndrome occurs when damage to the kidneys impairs their function, which allows protein from the blood to pass into the urine (proteinuria). Other signs and symptoms of nephrotic syndrome include increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells in the body (anemia), abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with nephrotic syndrome. If not treated with coenzyme Q10 supplementation, affected individuals eventually develop irreversible kidney failure (end-stage renal disease).

A type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy) can also occur in primary coenzyme Q10 deficiency.

Primary coenzyme Q10 deficiency is caused by mutations in genes that provide instructions for making proteins involved in the production (synthesis) of a molecule called coenzyme Q10. Collectively, they are called the COQ genes. Most of the identified mutations have occurred in the COQ2, COQ4, COQ6, COQ8A, and COQ8B genes. Smaller numbers of mutations in other COQ genes have also been found to cause primary coenzyme Q10 deficiency.

The coenzyme Q10 molecule has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Some mutations in the COQ genes greatly reduce or eliminate the production of the corresponding proteins; others change the structure of a protein, impairing its function. A lack of functional protein produced from any one of the COQ genes decreases the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Coenzyme Q10 deficiency can also be caused by mutations in genes that are not directly related to the synthesis of coenzyme Q10. In these cases, the condition is referred to as secondary coenzyme Q10 deficiency. Secondary coenzyme Q10 deficiency is a common feature of certain other genetic conditions.

Normal Function

The COQ2 gene provides instructions for making an enzyme that carries out one step in the production of a molecule called coenzyme Q10, which has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Multiple system atrophy

Several variations in the COQ2 gene have been suggested to increase the risk of multiple system atrophy, a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure.

The identified variations alter single protein building blocks (amino acids) in the COQ2 enzyme. Most of the variations are very rare, but a genetic change that replaces the amino acid valine with the amino acid alanine at position 393 (written as Val393Ala or V393A) is relatively common. Studies suggest that these variations, including V393A, are associated with an increased risk of developing multiple system atrophy in the Japanese population. However, studies have not found a correlation between COQ2 gene variations and multiple system atrophy in other populations, including Koreans, Europeans, and North Americans. It remains unclear whether COQ2 gene variations represent a significant risk factor for this disease.

Researchers speculate that changes in the COQ2 gene could impair the activity of the COQ2 enzyme, which would affect the production of coenzyme Q10. Levels of coenzyme Q10 are reduced in the brains of people with multiple system atrophy. However, the COQ2 gene variations associated with an increased risk of this disorder are thought to affect coenzyme Q10 levels less severely than the COQ2 gene mutations that cause primary coenzyme Q10 deficiency (described below). A reduction in the amount of coenzyme Q10 may impair cellular energy production from oxidative phosphorylation and increase the vulnerability of cells to damage from free radicals. However, it is unknown how these changes are related to the specific features of multiple system atrophy.

Primary coenzyme Q10 deficiency

At least nine mutations in the COQ2 gene have been found to cause a disorder known as primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys. The COQ2 gene mutations associated with this disorder greatly reduce or eliminate the production of the COQ2 enzyme, which prevents the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Other Names for This Gene

• 4-HB polyprenyltransferase
• 4-hydroxybenzoate decaprenyltransferase
• 4-hydroxybenzoate polyprenyltransferase, mitochondrial
• CL640
• coenzyme Q2 4-hydroxybenzoate polyprenyltransferase
• coenzyme Q2 homolog, prenyltransferase
• COQ10D1
• FLJ26072
• MSA1
• para-hydroxybenzoate-polyprenyltransferase, mitochondrial
• PHB:polyprenyltransferase
• PHB:PPT

Genomic Location

Normal Function

The COQ4 gene provides instructions for making a protein that is involved in the production of a molecule called coenzyme Q10, although its specific role in this process is unknown. Research suggests that the COQ4 protein may help organize other proteins involved in coenzyme Q10 production into a stable functional group (a protein complex).

Coenzyme Q10 has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Primary coenzyme Q10 deficiency

At least 12 mutations in the COQ4 gene have been found to cause a disorder known as primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys. The COQ4 gene mutations associated with this disorder greatly reduce or eliminate the production of the COQ4 protein, which prevents the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Other Names for This Gene

• CGI-92
• coenzyme Q biosynthesis protein 4 homolog
• coenzyme Q4 homolog
• COQ10D7
• ubiquinone biosynthesis protein COQ4 homolog, mitochondrial isoform 1 precursor
• ubiquinone biosynthesis protein COQ4 homolog, mitochondrial isoform 2 precursor

Genomic Location

Normal Function

The COQ6 gene provides instructions for making an enzyme that carries out one step in the production of a molecule called coenzyme Q10. Coenzyme Q10 has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Primary coenzyme Q10 deficiency

At least seven mutations in the COQ6 gene have been found to cause a disorder known as primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys. The COQ6 gene mutations associated with this disorder result in a COQ6 enzyme with an abnormal structure that likely impairs its function, leading to reduced production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Other Names for This Gene

• CGI-10
• CGI10
• coenzyme Q10 monooxygenase 6
• coenzyme Q6 homolog, monooxygenase
• COQ10D6
• ubiquinone biosynthesis monooxygenase COQ6, mitochondrial isoform a
• ubiquinone biosynthesis monooxygenase COQ6, mitochondrial isoform b

Genomic Location

Normal Function

The COQ8A gene provides instructions for making a protein that is involved in the production of a molecule called coenzyme Q10, which has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Primary coenzyme Q10 deficiency

At least 36 mutations in the COQ8A gene have been found to cause a disorder known as primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys. The COQ8A gene mutations associated with this disorder change the structure of the COQ8A protein or prevent its production, which impairs the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Other Names for This Gene

• aarF domain-containing protein kinase 3
• ADCK3
• ARCA2
• atypical kinase COQ8A, mitochondrial
• CABC1
• chaperone activity of bc1 complex-like, mitochondrial
• chaperone, ABC1 activity of bc1 complex homolog
• coenzyme Q protein 8A
• coenzyme Q8 homolog
• COQ10D4
• COQ8
• SCAR9

Genomic Location

Normal Function

The COQ8B gene provides instructions for making a protein that is involved in the production of a molecule called coenzyme Q10, which has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Primary coenzyme Q10 deficiency

At least 11 mutations in the COQ8B gene have been found to cause a disorder known as primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys. The COQ8B gene mutations associated with this disorder greatly reduce or eliminate the function of the COQ8B protein, which prevents the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

Other Names for This Gene

• aarF domain containing kinase 4
• aarF domain-containing protein kinase 4
• ADCK4
• atypical kinase COQ8B, mitochondrial isoform a
• atypical kinase COQ8B, mitochondrial isoform b
• coenzyme Q protein 8B
• COQ8
• FLJ12229
• NPHS9

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The prevalence of primary coenzyme Q10 deficiency is thought to be less than 1 in 100,000 people.