Molybdenum cofactor deficiency is a rare human disease in which the absence of

molybdopterin Molybdopterins are a class of cofactors found in most molybdenum-containing and all tungsten-containing enzymes. Synonyms for molybdopterin are: MPT and pyranopterin-dithiolate. The nomenclature for this biomolecule can be confusing: Molybdopteri ...

– and consequently its

molybdenum Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with le ...

complex, commonly called molybdenum cofactor – leads to accumulation of toxic levels of sulphite and neurological damage. Usually this leads 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 enzyme activity of

xanthine dehydrogenase Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the ''XDH'' gene. Function Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purine ...

oxidase In biochemistry, an oxidase is an enzyme that catalyzes oxidation-reduction reactions, especially one involving dioxygen (O2) as the electron acceptor. In reactions involving donation of a hydrogen atom, oxygen is reduced to water (H2O) or hydrogen ...

and aldehyde oxidase.

Cause

When caused by a mutation in the

MOCS1 Molybdenum cofactor biosynthesis protein 1 is a protein that in humans and other animals, fungi, and cellular slime molds, is encoded by the ''MOCS1'' gene. Both copies of this gene are defective in patients with molybdenum cofactor deficiency, ...

gene it is the type A variant. It can also be caused by a mutation in the MOCS2 gene or the

GEPH Gephyrin is a protein that in humans is encoded by the ''GPHN'' gene. This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subun ...

gene. As of 2010, there had been approximately 132 reported cases. It should not be confused with

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 does not occur in natural settings. However, it c ...

Diagnosis

Diagnosis of molybdenum cofactor deficiency includes early seizures, low blood levels of

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 a product of the metabolic breakdown ...

, and high levels of sulphite,

xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, ...

, and

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

. Additionally, the disease produces characteristic MRI images that can aid in diagnosis.

Treatment

Trials of an experimental treatment are going on at several sites in the US. https://www.centerwatch.com/clinical-trials/listings/84057/molybdenum-cofactor-deficiency-type-a-study-alxn1101-neonates-molybdenum/ On 26 February 2021, the U.S. Food and Drug Administration approved

fosdenopterin Fosdenopterin (or cyclic pyranopterin monophosphate, cPMP), sold under the brand name Nulibry, is a medication used to reduce the risk of death due to a rare genetic disease known as molybdenum cofactor deficiency type A. The most common sid ...

(Nulibry) for intravenous injection to reduce the risk of death due to Molybdenum Cofactor Deficiency Type A. Fosdenopterin replaces the missing cyclic pyranopterin monophosphate (cPMP).

Prevalence

The prevalence of molybdenum co-factor deficiency is estimated as being between 1 in 100 000 and 1 in 200 000. To date more than 100 cases have been reported. However, this may significantly under represent cases.

Research

In 2009,

Monash Children's Hospital Monash Children's Hospital is a major children's hospital in Melbourne, Australia. Monash Children's Hospital is part of Monash Health, Victoria's largest healthcare service and one of only four accredited Academic Health Science Centres in Au ...

at Southern Health in Melbourne, Australia reported that a patient known as Baby Z became the first person to be successfully treated for molybdenum cofactor deficiency type A. The patient was treated with cPMP, a precursor of molybdopterin. Baby Z will require daily injections of

cyclic pyranopterin monophosphate Fosdenopterin (or cyclic pyranopterin monophosphate, cPMP), sold under the brand name Nulibry, is a medication used to reduce the risk of death due to a rare genetic disease known as molybdenum cofactor deficiency type A. The most common sid ...

(cPMP) for the rest of her life.

References

External links

{{Metabolic disorders of vitamins, coenzymes, and cofactors Vitamin, coenzyme, and cofactor metabolism disorders