Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. Molybdenum cofactor deficiency mocd is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, 1 of 4 molybdenum. Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are serious and often fatal diseases for which no effective therapy is generally available. Molybdenum cofactor deficiency is a rare autosomal recessive disorder with devastating neurological manifestations, characterised. Furthermore, a mutational block in molybdenum cofactor. Maintenance of diseaserelevant biomarker improvement in patients.
Hartmut koch1 reports a case of molybdenum cofactor deficiency in which the diagnosis was delayed because of a falsenegative urine sulphite test. Molybdenum compounds appear to have a low toxicity in 3 humans. This disorder prevents the body from using molybdenum. Molybdenum is a cofactor required for the functions of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase enzymes for humans. Substrate substitution therapy has successfully been performed in single cases of mocd type a and. One type of scaffold is the ubiquitous pterinbased molybdenum cofactor. Several mutations have been observed in genes encoding for molybdopterin. Feb 18, 2019 molybdenum cofactor deficiency and isolated sulfite oxidase deficiency.
A mutation in the gene for the neurotransmitter receptorclustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Molybdopterin, the organophosphatedithiolate ligand that binds mo and w in most molybdenum. To evaluate molybdenum cofactor deficiency mocd disease biomarkers in urine and plasma in patients with mocd type a treated with synthetic. Sulfite oxidase deficiency and molybdenum cofactor deficiency. Click here to buy this book in print or download it as a free pdf. Deficiencies nutritional deficiency induced by low dietary molybdenum has never been observed in humans to our knowledge. Molybdenum is a structural constituent of molybdopterin, a cofactor. Human moco deficiency mocd results in the complete loss of sulphite oxidase, xanthine. Mass spectrometric analysis verified and quantitated ssulphocysteine. Pdf spherophakia associated with molybdenum cofactor.
Usually this leads to death within months of birth, due to the lack of active sulfite oxidase. Abstract the clinical, biochemical, and neuropathological findings in two neonates with molybdenum cofactor deficiency presenting with convulsions are reported from the academic medical center, amsterdam, the netherlands. The pharmaceutical challenges of cyclic pyranopterin monophosphate cpmp aims to provide a brief overview of the disease, molybdenum cofactor deficiency mocd and its prognosis. Molybdenum cofactor moco deficiency mim 252150 in human results in untreatable neonatal seizures and other neurological symptoms identical to those of sulfite oxidase deficiency. Mocd results in deficiency of the molybdenum cofactor dependent enzymes. Molybdenum cofactor deficiency phenotypic variability in a family with a lateonset variant. Molybdenum deficiency symptoms are more likely to occur because of a rare genetic disorder in the production of molybdopterin. Molybdenum cofactor deficiency genetic and rare diseases nih. A deficiency of the cofactor in humans dimimishes the ability to synthesise those enzymes of which the cofactor. In this report, we describe a threemonthold infant.
Restoration of molybdenum cofactor dependent enzyme activities results in a greatly improved. A case of molybdenum cofact or deficiency sri lanka jou rnal of child health, 2017. Molybdenum cofactor deficiency is an autosomal recessive disorder characterized by lack of activity of the enzymes sulfite oxidase, aldehyde oxidase, and xanthine dehydrogenase or oxidase. We examined the clinical, brain mri, biochemical, genetic, and electroencephalographic features and outcome in 8 children with a diagnosis of molybdenum cofactor deficiency observed in our institution over 10 years. The absence of active sulfite oxidasea molybdenum cofactordependent enzymeresults in neonatal seizures and early childhood death. Molybdenum cofactor deficiency synonyms, molybdenum cofactor. Combined deficiency of sulfite oxidase, xanthine dehydrogenase, and. Molybdenum cofactor deficiency in a malaysian child singapore. Clinical features of molybdenum cofactor deficiency, e. Molybdenum cofactordeficient mice resemble the phenotype.
Surprisingly, molybdenum itself is catalytically inactive in biological systems until it is complexed by a special scaffold. Abstract we report a case of genetically confirmed molybdenum cofactor deficiency. Pdf a case of molybdenum cofactor deficiency researchgate. It can cause seizures and severe brain damage that usually leads to death within days after birth. Molybdenum deficiency an overview sciencedirect topics. Molybdenum cofactor deficiency is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, one of four molybdenum. The transition element molybdenum is an essential micronutrient for microorganisms, plants, and animals. Molybdenum cofactor deficiency predominantly affects the central nervous system. Molybdenum cofactor deficiency mocd is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor retardation, dysmorphic. There are limited toxicity data for molybdenum in humans.
A retrospective, observational, noninterventional data. Effect of sulfite on cognitive functions in normal and sulfite oxidase deficient rats. Nyhan and others published molybdenum cofactor deficiency find, read and cite all the research you need on researchgate. A retrospective, observational, noninterventional data collection study for patients with molybdenum cofactor deficiency who have been previously treated with cyclic pyranopterin monophosphate cpmp the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. May 10, 20 the transition element molybdenum needs to be complexed by a special cofactor to gain catalytic activity. Naturally occurring cpmp is present in the body of all healthy normal individuals. The transition element molybdenum needs to be complexed by a special cofactor to gain catalytic activity.
This condition is called molybdenum cofactor deficiency. Molybdenum cofactor moco deficiency leads to a combined deficiency of the molybdo. Without the activity of one or both of these proteins, molybdenum cofactor biosynthesis is impaired. Ssulfocysteinenmda receptordependent signaling underlies neurodegeneration in molybdenum cofactor deficiency avadh kumar, guenter schwarz, abdel ali belaidi published december 1, 2017. Molybdenum cofactor deficiency mocd is a rare metabolic disorder 1, 2 characterized by severe neurological abnormalities including intractable neonatal seizures, feeding difficulties, developmental delay, ocular lens dislocation, and death in early childhood. Molybdenum cofactor deficiency molybdenum cofactor deficiency mocd is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor retardation. Methods mocd is an inherited metabolic disease in which the molybdenum dependant. Investigation of molybdenum cofactor deficiency due. Two years experience of the treatment of molybdenum.
Molybdenum cofactor deficiency mocd is a rare metabolic disorder 1, 2 characterized by severe neurological abnormalities including intractable neonatal seizures, feeding difficulties, developmental. Synonyms for molybdenum cofactor deficiency in free thesaurus. Molybdenum cofactor deficiency mocd is a severe auto somal recessive neonatal metabolic disease that causes seizures. Without the activity of one or both of these proteins, molybdenum cofactor. Molybdenum cofactor deficiency is a rare condition that is estimated to occur in 1 in 100,000 to 200,000 newborns worldwide.
To share the experiences and challenges in the sourcing, storage, manipulation, supply and administration of the novel product cpmp. Efficacy and safety of cyclic pyranopterin monophosphate. The resultant accumulation of sulfite, taurine, ssulfocysteine and thiosulfate contributes to the severe neurological impairment. If you have problems viewing pdf files, download the latest version of adobe reader. Critical appraisal of genotype assessment in molybdenum. Johnson jl, wadman sk 1989 molybdenum cofactor deficiency. Molybdenum cofactor deficiency is a rare metabolic disorder manifesting with early onset seizures, developmental delay, microcephaly, and spasticity. Click on the link to view a sample search on this topic. Molybdenum cofactor an overview sciencedirect topics.
Molybdenum cofactor deficiency mimics cerebral palsy. Molybdenum cofactor deficiency mocd is an ultraorphan, lifethreatening disease. A molybdenum cofactor is a biochemical cofactor that contains molybdenum examples include. No therapy is known for this rare disease, which results in neonatal seizures and other neurological symptoms identical to sulphite oxidase deficiency. Molybdenum is bound to a unique pterin, thus forming the molybdenum cofactor moco, which, in different variants, is the active compound at the catalytic site of all molybdenum containing enzymes in nature, except bacterial molybdenum. A congenital molybdenum cofactor deficiency disease, seen in infants, results in interference with the ability of the body to use molybdenum in enzymes. Enable javascript to view the expandcollapse boxes. Molybdenum cofactor deficiency and isolated sulfite. Two years experience of the treatment of molybdenum cofactor.
Until recently, no effective therapy was available, and early fatality was the usual outcome. There are limited data on longterm outcome or brain magnetic resonance imaging mri features. Study of cpmp precusor z to treat molybdenum cofactor. Molybdenum cofactor deficiency definition of molybdenum.
Few infants with this defect survive the first days of life, and those who do have severe neurological and other abnormalities. Some patients, especially those with milder forms of isolated sulfite oxidase deficiency. It is processed to molybdopterin, which is further processed to molybdenum cofactor. Although more than 100 genetically characterized patients have been reported, this number is discrepant with the actual. Molybdenum is bound to a unique pterin, thus forming the molybdenum cofactor moco, which, in different variants, is the active compound at the. One type of scaffold is the ubiquitous pterinbased molybdenum cofactor moco, 2 which, in different variants, forms part of the active centers of. Hartmut koch dec 5, p 18241 rightly draws attention to two points about correct diagnosis of molybdenum cofactor deficiency. Molybdenum cofactor deficiency type a mocd is a very rare autosomal recessive disorder that is essentially fatal early in life. Clinical neuroimaging features and outcome in molybdenum.
Diagnosis of molybdenum cofactor deficiency the lancet. If you have problems viewing pdf files, download the latest version of adobe. Molybdenum cofactordeficient mice resemble the phenotype of. The metabolic and molecular bases of inherited disease. A rare meta bolic defect called molybdenum cofactor deficiency results from the deficiency of molybdoenzymes. Prenatal diagnosis of molybdenum cofactor deficiency and. Human molybdenum cofactor deficiency is a rare and devastating autosomalrecessive disease for which no therapy is known. First published november 6, 2017 citation information. From studies of cocultured fibroblasts from affected individuals, johnson et al.
We describe a new case of molybdenum cofactor deficiency, an. We support his call for measurement of serum uric acid during investigation of neonatal seizures, since hypouricaemia is the most consistent biochemical feature of this unusual disorder. Molybdenum is bound to a unique pterin, thus forming the molybdenum cofactor moco, which, in different variants, is the active compound at the catalytic site of all molybdenum containing enzymes in nature, except bacterial molybdenum nitrogenase. Molybdenum is an essential trace element that is naturally present in many foods and is also available as a dietary supplement. More than 100 cases have been reported in the medical literature, although it is. Molybdenum deficiency has been produced in goats when on a diet with a molybdenum content of only 24. The form of molybdenum cofactor deficiency caused by mutation in mocs1 is called here complementation group a not type a.
Aug 12, 2009 molybdenum cofactors, enzymes and pathways. In molybdenum deficiency, activities of these 3 enzymes decrease. Information specialists for molybdenum cofactor deficiency. Aug 12, 2009 molybdenum cofactor deficiency type a mocd is a very rare autosomal recessive disorder that is essentially fatal early in life. The molybdenum cofactor deficiency is an autosomal recessive disease, characterized by rapidly progressive and severe neurological damage that mimics a hypoxicischemic encephalopathy due to the accumulation of toxic metabolites that cause rapid neurodegeneration after the delivery. The journal of tepecik education and research hospital. A mild case of molybdenum cofactor deficiency defines an alternative route of mocs1 protein maturation.
It has been induced in chicks and rats, but only after tungsten was added at a ratio of. Molybdenum cofactor deficiency mocd is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor retardation, dysmorphic facies, and dislocated ocular lenses. It happens only in people with a very rare genetic disorder called molybdenum cofactor deficiency. For language access assistance, contact the ncats public information officer. Molybdenum cofactor deficiency type a molybdenum cofactor deficiency mocd is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, 1 of 4 molybdenum dependent enzymes. A rare and usually fatal metabolic defect called molybdenum cofactor deficiency results from the deficiency of molybdoenzymes.
Our patient, a 2yearold boy, presented with spastic quadriplegia and mental retardation. Until recently the disorder always was fatal early in life. May 01, 2020 pubmed is a searchable database of medical literature and lists journal articles that discuss molybdenum cofactor deficiency. Molybdenum cofactor deficiency article about molybdenum. Jci ssulfocysteinenmda receptordependent signaling. Mohamed, elamin ahmed department of pediatrics, division of child neurology, sheikh khalifa medical city, abu dhabi, u. 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.
Molybdenum cofactor deficiency mocd is a severe autosomal recessive inborn error of metabolism first described in 1978. Mocd results in deficiency of the molybdenum cofactor dependent enzymes sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase and mitochondrial amidoxime reducing component. Journal of evidencebased molybdenum nutriture in humans. Femoco, a metal cluster that contains fe, mo, and s that is found in some nitrogenases. Molybdenum cofactor deficiency genetic and rare diseases. The association of molybdenum cofactor deficiency and pyloric. We describe an infant with molybdenum cofactor deficiency, initially diagnosed as cerebral palsy.
Molybdenum cofactor deficiency genetics home reference nih. Four genes mocs1, mocs2, mocs3, and geph are needed for the production pathway of molybdenum cofactor. All molybdenum mocontaining enzymes in man, animals, plants, archaea and bacteriawith the sole exception of the prokaryotic nitrogenaserequire a cofactor consisting of an organic moiety, called molybdopterin mpt, and mo. Mar 12, 2015 molybdenum cofactor deficiency has its onset during the neonatal period and infancy. Report of three cases presenting as hypoxic ischemic encephalopathy meral topcu, md, turgay coskun, md, goknur haliloglu, md, and isil saatci, md journal of child neurology 2016 16. Molybdopterin, the organophosphatedithiolate ligand that binds mo and w in most molybdenum except nitrogenases and all tungstencontaining proteins. It is much more common than molybdenum cofactor deficiency but is not a lethal defect.
Johnson and rajagopalan 1982 showed that urothione, a sulfurcontaining pterin, is the normal metabolic degradation product of the molybdenum cofactor that is deficient in this disorder. Pubmed is a searchable database of medical literature and lists journal articles that discuss molybdenum cofactor deficiency. A molybdenum cofactor is a biochemical cofactor that contains molybdenum. Molybdenum cofactor deficiency is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, one of four molybdenum dependent enzymes. Rescue of lethal molybdenum cofactor deficiency by a. Molybdenum cofactor deficiency is a rare human disease in which the absence of molybdenum cofactor leads to accumulation of toxic levels of sulphite and neurological damage. Scriver cr, beaudet al, sly ws, valle dl eds metabolic basis of inherited disease, 6th edn. Molybdenum cofactor deficiency type a disease page.