Cytochrome c oxidase deficiency

Rare Endocrinology News

Disease Profile

US Estimated

Europe Estimated

Age of onset

-

ICD-10

E88.8

Inheritance

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Mitochondrial complex IV deficiency; Complex 4 mitochondrial respiratory chain deficiency; Deficiency of mitochondrial respiratory chain complex4;

Summary

Cytochrome C oxidase deficiency (COX deficiency) is a condition that can affect several parts of the body including the skeletal muscles, heart, brain and liver. There are four types of COX deficiency differentiated by symptoms and age of onset: benign infantile mitochondrial type, French-Canadian type, infantile mitochondrial myopathy type, and Leigh syndrome.^[1] The range and severity of signs and symptoms can vary widely among affected individuals (even within the same subtype and same family) and depend on the form of the condition present. Features in mildly affected individuals may include muscle weakness and hypotonia; in more severely affected individuals, brain dysfunction; heart problems; an enlarged liver; lactic acidosis; and/or a specific group of features known as Leigh syndrome may also be present. COX deficiency is caused by mutations in any of at least 14 genes; the inheritance pattern depends on the gene involved. The condition is frequently fatal in childhood, but mildly affected individuals may survive into adolescence or adulthood.^[2]

Symptoms

There are currently 4 known forms of COX deficiency. The range and severity of signs and symptoms can vary widely from case to case.

In one form, referred to as the benign infantile mitochondrial myopathy type, symptoms may be limited to the skeletal muscles. Episodes of lactic acidosis may occur and can cause life-threatening complications if left untreated. However, with appropriate treatment, individuals with this form of the condition may spontaneously recover within the first few years of life.^[1]

In the second form of the disorder, referred to as the infantile mitochondrial myopathy type, the skeletal muscles as well as several other tissues (such as the heart, kidney, liver, brain, and/or connective tissue) are affected. Symptoms associated with this form typically begin within the first few weeks of life and may include muscle weakness; heart problems; kidney dysfunction; failure to thrive; difficulties sucking, swallowing, and/or breathing; and/or hypotonia. Affected infants may also have episodes of lactic acidosis.^[1]

The third form of COX deficiency is thought to be a systemic form of the condition and is referred to as Leigh's disease. This form is characterized by progressive degeneration of the brain as well as dysfunction of several other organs including the heart, kidneys, muscles, and/or liver. Symptoms of this form, which predominantly involve the central nervous system, may begin between three months and two years of age and may include loss of previously acquired motor skills and/or head control; poor sucking ability; loss of appetite; vomiting; irritability; and possible seizures. Intellectual disability may also occur.^[1]

In the fourth form of COX deficiency, the French-Canadian type, the brain (as in Leigh's disease) and liver are particularly affected in addition to the skeletal muscles and connective tissues. However, in this form, the kidneys and heart appear to have near-normal enzyme activity. Individuals with this form may have developmental delay; hypotonia; slight facial abnormalities; Leigh's disease; strabismus; ataxia; liver degeneration; and/or episodes of lactic acidosis.^[1]

Although some mildly affected individuals survive into adolescence or adulthood, this condition is often fatal in childhood.^[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Aminoaciduria	High urine amino acid levels Increased levels of animo acids in urine [ more ]	0003355
Anemia	Low number of red blood cells or hemoglobin	0001903
Ataxia		0001251
Autosomal recessive inheritance		0000007
Cytochrome C oxidase-negative muscle fibers		0003688
Decreased liver function	Liver dysfunction	0001410
Exercise intolerance	Decreased ability to exercise Inability to exercise [ more ]	0003546
Exertional dyspnea		0002875
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
Glycosuria	Glucose in urine	0003076
Hepatomegaly	Enlarged liver	0002240
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hyperphosphaturia	High urine phosphate levels	0003109
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Increased CSF lactate		0002490
Increased hepatocellular lipid droplets		0006565
Increased intramyocellular lipid droplets		0012240
Increased serum lactate		0002151
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Lactic acidosis	Increased lactate in body	0003128
Leukoencephalopathy		0002352
Mitochondrial inheritance		0001427
Motor delay		0001270
Muscular hypotonia	Low or weak muscle tone	0001252
Optic atrophy		0000648
Pigmentary retinopathy		0000580
Proteinuria	High urine protein levels Protein in urine [ more ]	0000093
Ptosis	Drooping upper eyelid	0000508
Renal Fanconi syndrome		0001994
Respiratory distress	Breathing difficulties Difficulty breathing [ more ]	0002098
Respiratory insufficiency due to muscle weakness	Decreased lung function due to weak breathing muscles	0002747
Seizure		0001250
Sensorineural hearing impairment		0000407
Weakness of facial musculature	Decreased facial muscle strength Decreased strength of facial muscles Face weakness Facial muscle weakness Facial weakness Reduced facial muscle strength Weakness of face [ more ]	0030319

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Treatment

There is currently no cure for cytochrome C oxidase (COX) deficiency. Management of all forms of COX deficiency generally focuses on the specific symptoms present in the affected individual and is largely supportive. The goals of treatment are to improve symptoms and slow progression of the disease; the effectiveness of treatment varies with each individual.^[3]^[4] Treatment generally does not reverse any damage that has already occurred.^[3] Prognosis varies depending on the form of COX deficiency present.^[4] Individuals with benign infantile mitochondrial myopathy may experience spontaneous recovery (although early diagnosis and intensive treatment is still needed until this point), while there may be rapid demise in individuals with Leigh syndrome.^[4]

It is often recommended that individuals with mitochondrial disorders such as COX deficiency avoid fasting. Dehydration due to vomiting or illness may be treated with intravenous fluid if the individual is not able to take fluids orally. Seizures are typically controlled with anticonvulsants. Some affected individuals may benefit from physical, occupational, and speech therapies that are specifically tailored to their needs.^[3] Dietary supplements including certain vitamins and cofactors have shown varying degrees of benefit in individual cases.^[4]

Individuals interested in specific management recommendations for themselves or relatives should speak with their healthcare providers.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

MitoAction
PO Box 310
Novi, MI 48376
Toll-free: 888-648-6228
E-mail: info@mitoaction.org
Website: https://www.mitoaction.org/
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MedlinePlus Genetics contains information on Cytochrome c oxidase deficiency. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The United Mitochondrial Disease Foundation has an information page on Cytochrome c oxidase deficiency.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
PubMed is a searchable database of medical literature and lists journal articles that discuss Cytochrome c oxidase deficiency. Click on the link to view a sample search on this topic.

References

Cytochrome C Oxidase Deficiency. NORD. 2015; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1088/viewAbstract. Accessed 4/17/2013.
Cytochrome c oxidase deficiency. Genetics Home Reference. October 2012; https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency. Accessed 4/17/2013.
Gropman AL. Diagnosis and treatment of childhood mitochondrial diseases. Curr Neurol Neurosci Rep. March 2001; 1(2):185-194.
PATRICK F. CHINNERY. Chapter 429: Muscle Diseases. GOLDMAN'S CECIL MEDICINE, 24TH EDITION. Philadelphia, PA: Saunders; 2011;

Rare Endocrinology News

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Rare Endocrinology News

-

E88.8

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Treatment

Organizations

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

Rare Endocrinology News

Rare Endocrinology News

-

E88.8

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Treatment

Organizations

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.