Molybdenum cofactor deficiency
Encyclopedia
Molybdenum cofactor deficiency is a human disease. Absence of molybdenum cofactor
leads to accumulation of toxic levels of sulphite and neurological damage usually leading to death within months of birth, due to the lack of active sulfite oxidase
. Furthermore a mutational block in molybdenum cofactor
biosynthesis causes absence of enyzme activity of xanthine dehydrogenase/oxidase and aldehyde oxidase
.
When caused by a mutation in the MOCS1
gene it is the type A variant.
It can also be caused by a mutation in the MOCS2
gene, and in the GEPH gene.
It should not be confused with molybdenum deficiency
.
As of 2010, there had been approximately 132 reported cases.
, and high levels of sulphite, xanthine
and uric acid
in urine
. Characteristic MRI images of brain.
, a precursor of the molybdenum cofactor
. Baby Z will require daily injections of cyclic pyranopterin monophosphate
(cPMP) for the rest of her life.
Molybdenum cofactor
Molybdenum cofactor is a cofactor required for the activity of enzymes such as sulfite oxidase, xanthine oxidoreductase, and aldehyde oxidase. It is a coordination complex formed between molybdopterin and an oxide of molybdenum.Molybdopterins, in turn, are synthesized from guanosine triphosphate...
leads to accumulation of toxic levels of sulphite and neurological damage usually leading to death within months of birth, due to the lack of active sulfite oxidase
Sulfite oxidase
Sulfite oxidase is an enzyme in the mitochondria of all eukaryotes. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation...
. Furthermore a mutational block in molybdenum cofactor
Molybdenum cofactor
Molybdenum cofactor is a cofactor required for the activity of enzymes such as sulfite oxidase, xanthine oxidoreductase, and aldehyde oxidase. It is a coordination complex formed between molybdopterin and an oxide of molybdenum.Molybdopterins, in turn, are synthesized from guanosine triphosphate...
biosynthesis causes absence of enyzme activity of xanthine dehydrogenase/oxidase and aldehyde oxidase
Aldehyde oxidase
Aldehyde oxidase is an enzyme which generates carboxylic acids from aldehydes. It catalyzes the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide.* an aldehyde + H2O + O2 a carboxylate + H2O2 + H+...
.
When caused by a mutation in the MOCS1
MOCS1
Molybdenum cofactor biosynthesis protein 1 is a protein that in humans is encoded by the MOCS1 gene.Both copies of this gene are defective in patients with molybdenum cofactor deficiency, type A.-Further reading:...
gene it is the type A variant.
It can also be caused by a mutation in the MOCS2
MOCS2
Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene...
gene, and in the GEPH gene.
It should not be confused with molybdenum deficiency
Molybdenum deficiency
Molybdenum deficiency refers to the clinical consequences of inadequate supplies of molybdenum in the diet.The amount of molybdenum required is relatively small, and molybdenum deficiency usually doesn't occur in natural settings. However, it can occur in individuals receiving parenteral nutrition....
.
As of 2010, there had been approximately 132 reported cases.
Diagnosis
Early seizures, low blood levels of uric acidUric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, and high levels of sulphite, xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
and uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
in urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. Characteristic MRI images of brain.
Breakthrough
In 2009, the first person to be cured of molybdenum cofactor deficiency type A, Baby Z has made world medical and legal history for Monash Children's at Southern Health in Melbourne, Australia. The patient was treated with cPMPCyclic pyranopterin monophosphate
Cyclic pyranopterin monophosphate is an experimental treatment for molybdenum cofactor deficiency type A, which was developed by the pioneering work of Jose Santamaría-Araujo, PhD and Prof.Dr...
, a precursor of the molybdenum cofactor
Molybdenum cofactor
Molybdenum cofactor is a cofactor required for the activity of enzymes such as sulfite oxidase, xanthine oxidoreductase, and aldehyde oxidase. It is a coordination complex formed between molybdopterin and an oxide of molybdenum.Molybdopterins, in turn, are synthesized from guanosine triphosphate...
. Baby Z will require daily injections of cyclic pyranopterin monophosphate
Cyclic pyranopterin monophosphate
Cyclic pyranopterin monophosphate is an experimental treatment for molybdenum cofactor deficiency type A, which was developed by the pioneering work of Jose Santamaría-Araujo, PhD and Prof.Dr...
(cPMP) for the rest of her life.