Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study

  title={Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study},
  author={Bernd C Schwahn and Francjan J. van Spronsen and Abdelhak Belaidi and Stephen Bowhay and John Christodoulou and Terry G. J. Derks and Julia B. Hennermann and Elisabeth A. Jameson and Kai K{\"o}nig and Tracy L. McGregor and Esperanza Font-Montgomery and José Angel Santamaria-Araujo and Saikat Santra and Mamta Vaidya and Anne Vierzig and Evangeline Wassmer and Ilona Weis and Flora Y. Wong and Alex Veldman and Gunter Schwarz},
  journal={The Lancet},

Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system

It is suggested that to achieve optimal reductions in morbidity and mortality, rWGS must be implemented within a comprehensive rapid precision medicine system (CRPM).

Rare cause of xanthinuria: a pediatric case of molybdenum cofactor deficiency B

Molybdenum cofactor deficiencies should be considered in neonates with early-onset seizures, hypotonia, and feeding difficulties, and Screening with serum uric acid levels and empiric treatment may be considered while awaiting genetic results.

A neonate with molybdenum cofactor deficiency type B

The patients with MOCS2 who onset in neonatal period often shows uncontrolled seizure, feeding difficulties, hypotonia and early death, and the MRI of them shows severe encephalomalacia.

Molybdenum Cofactor Deficiency in Humans

In the absence of a specific treatment for MoCD type B/C and SOX deficiency, recent progress is summarized in the understanding of the underlying metabolic changes in cysteine homeostasis and proposed novel therapeutic interventions to circumvent those pathological changes.

Critical appraisal of genotype assessment in molybdenum cofactor deficiency

The severity of the genotype assessed by in silico prediction and further classification explained survival in molybdenum cofactor deficiency may therefore be considered a confounder for the outcome of therapeutic clinical trials requiring adjustment in the clinical trial design or analysis.

Expanding the Phenotype of Molybdenum Cofactor Deficiency in Neonates: Report of Two Cases

Molybdenum cofactor deficiency presenting as hypoxic-ischemic encephalopathy and cerebral palsy are well described, but its presentation in preterm with “sepsis-like features with drug-responsive seizures” in the early newborn period is not described and can also cause unnecessary delay in the diagnosis.

Molybdenum cofactor deficiency: A natural history

Delineation of MoCD natural history supports evaluations of emerging replacement therapy with cPMP for MoCD‐A, which may modify disease course for affected individuals.

Molybdenum cofactor deficiency.

A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation

A patient with an unusual late disease onset and mild phenotype is reported, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder, which demonstrates an unusual mechanism of translation re-initiation in the MOCS1 transcript being sufficient to partially protect the patient from the most severe symptoms of MoCD.



Successful Treatment of Molybdenum Cofactor Deficiency Type A With cPMP

Substitution of cPMP represents the first causative therapy available for patients with molybdenum cofactor cofactor–dependent enzyme activities, and it is demonstrated efficient uptake of c PMP and restoration of molyBdenum Cofactor– dependent enzyme activities are demonstrated.

Favorable Outcome in a Newborn With Molybdenum Cofactor Type A Deficiency Treated With cPMP

It is demonstrated that a daily cPMP dose of even 80 μg/kg in the first 12 days reduced the effects of neurodegenerative damage even when seizures and cramped-synchronized GMs were already present.

Molybdenum cofactor deficiency: a new HPLC method for fast quantification of s-sulfocysteine in urine and serum.

A fast and sensitive method for the analysis of SSC in human urine samples using high performance liquid chromatography (HPLC) that represents a cost-effective technique for routine diagnosis of MoCD and SOD, and can be used also to monitor treatment efficiency in those sulfite toxicity disorders on a daily basis.

Defective molybdopterin biosynthesis: clinical heterogeneity associated with molybdenum cofactor deficiency

Data indicate a functionally inadequate terminal enzyme for converting precursor Z to active molybdopterin (complementation group B of general molybdenum cofactor deficiency) and the patient has survived into the third decade with a less severe clinical spectrum than has generally been associated with this disease.

Timing of Cerebral Developmental Disruption in Molybdenum Cofactor Deficiency

Given the dramatic acceleration of decay of the subcortical white matter after the cord is clamped, the rapid onset of clinical symptoms after birth and the fast clinical deterioration after birth, it is postulate that maternal-placental clearance of sulfite is quite effective until late pregnancy in the majority of cases.

Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.

Findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.

Molybdenum cofactor biosynthesis and deficiency

  • G. Schwarz
  • Chemistry, Biology
    Cellular and Molecular Life Sciences CMLS
  • 2005
Human Moco deficiency is a hereditary metabolic disorder characterized by severe neurodegeneration resulting inEarly childhood death resulting in early childhood death and a first substitution therapy was established.

Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2

All molybdenum‐containing enzymes other than the bacterial nitrogenase share an identical molybdenum cofactor (MoCo), which is synthesized via a conserved pathway in all organisms and therefore also

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

All patients with identified mutations are either homozygous or compound heterozygous for mutations in either of the two open reading frames corresponding to MOCS1 A and M OCS1 B, respectively, suggesting the existence of more than the two previously described complementation groups in MoCo biosynthesis.