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Molybdenum cofactor deficiency
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Reviewed March 2014
What is molybdenum cofactor deficiency?
Molybdenum cofactor deficiency is a rare condition characterized by brain dysfunction (encephalopathy) that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment (intractable seizures). Brain abnormalities, including deterioration (atrophy) of brain tissue, lead to severe developmental delay; affected individuals usually do not learn to sit unassisted or to speak. A small percentage of affected individuals have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises. Other features of molybdenum cofactor deficiency can include a small head size (microcephaly) and facial features that are described as "coarse."
Tests reveal that affected individuals have high levels of chemicals called sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine and low levels of a chemical called uric acid in the blood.
Because of the serious health problems caused by molybdenum cofactor deficiency, affected individuals usually do not survive past early childhood.
How common is molybdenum cofactor deficiency?
Molybdenum cofactor deficiency is a rare condition that is estimated to occur in 1 in 100,000 to 200,000 newborns worldwide. More than 100 cases have been reported in the medical literature, although it is thought that the condition is underdiagnosed, so the number of affected individuals may be higher.
What genes are related to molybdenum cofactor deficiency?
Molybdenum cofactor deficiency is caused by mutations in the MOCS1, MOCS2, or GPHN gene. There are three forms of the disorder, named types A, B, and C (or complementation groups A, B, and C). The forms have the same signs and symptoms but are distinguished by their genetic cause: MOCS1 gene mutations cause type A, MOCS2 gene mutations cause type B, and GPHN gene mutations cause type C. The proteins produced from each of these genes are involved in the formation (biosynthesis) of a molecule called molybdenum cofactor. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes. These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized.
Mutations in the MOCS1, MOCS2, or GPHN gene reduce or eliminate the function of the associated protein, which impairs molybdenum cofactor biosynthesis. Without the cofactor, the metabolic enzymes that rely on it cannot function.
The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine (which can be identified in urine), and low levels of uric acid in the blood. Sulfite, which is normally broken down by one of the molybdenum cofactor-dependent enzymes, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency.
How do people inherit molybdenum cofactor deficiency?
Molybdenum cofactor deficiency has an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. An affected individual usually inherits one altered copy of the gene from each parent. Parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition.
At least one individual with molybdenum cofactor deficiency inherited two mutated copies of the MOCS1 gene through a mechanism called uniparental isodisomy. In this case, an error occurred during the formation of egg or sperm cells, and the child received two copies of the mutated gene from one parent instead of one copy from each parent.
Where can I find information about diagnosis or management of molybdenum cofactor deficiency?
These resources address the diagnosis or management of molybdenum cofactor deficiency and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about molybdenum cofactor deficiency?
You may find the following resources about molybdenum cofactor deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for molybdenum cofactor deficiency?
What if I still have specific questions about molybdenum cofactor deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding molybdenum cofactor deficiency?
aldehyde ; atrophy ; autosomal ; autosomal recessive ; cell ; cofactor ; deficiency ; dehydrogenase ; developmental delay ; egg ; encephalopathy ; enzyme ; gene ; inheritance ; inherited ; microcephaly ; molecule ; oxidase ; pattern of inheritance ; protein ; recessive ; sperm ; tissue ; toxic ; uric acid
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (5 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.