RARE DISEASE
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Synonyms: Combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type A, MOCOD type A
Synonyms: Combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type A, MOCOD type A
Synonyms: Combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type A, MOCOD type A
Drug discovery
2
drugs
With orphan designations
Overview
Sulfite Oxidase Deficiency Due to Molybdenum Cofactor Deficiency Type A (MoCD-A) is a rare, autosomal recessive neurometabolic disorder caused by MOCS1 mutations, impairing molybdenum cofactor (MoCo) biosynthesis. This disrupts sulfite oxidase activity, leading to toxic sulfite accumulation. Neonates present with intractable seizures, feeding difficulties, and progressive encephalopathy within days of birth. Lens dislocation, spastic quadriplegia, and cystic brain lesions on MRI are common [1][5][8]. Early cPMP (fosdenopterin) replacement can mitigate neurological decline if initiated promptly [1][9].
Key Clinical Insights
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders
Research Papers
39 drug discovery papers about Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
39 drug discovery papers about Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-02-09 | Autism Spectrum Disorder and Long-Term Survival in Attenuated Molybdenum Cofactor Deficiency Type A: A Case Report From Saudi Arabia.
We report the case of an 18-year-old male with genetically confirmed molybdenum cofactor deficiency type A (MoCD-A) due to a homozygous pathogenic MOCS1 variant. He presented in infancy with hypotonia and developmental delay and experienced a generalized tonic seizure at 20 months of age, followed by long-term seizure remission. His clinical course was notable for preserved motor function, below-average cognitive ability, marked speech delay, autism spectrum disorder (ASD), and prominent inattentive symptoms. Metabolic testing demonstrated elevated urinary xanthine, hypoxanthine, and S-sulfocysteine levels, supporting impaired sulfite oxidase activity. Neuroimaging revealed a small, focal hypodensity in the left basal ganglia without progressive changes. This case illustrates an attenuated phenotype of MoCD-A, with survival into adulthood and detailed neuropsychiatric characterization, expanding the recognized clinical spectrum and underscoring the importance of considering metabolic etiologies in patients with overlapping developmental and behavioral features.
2025-05-05 | Perioperative Care of a Child With Molybdenum Cofactor Deficiency.
Molybdenum is a trace mineral that is a key component of several enzyme systems. In the human body, molybdenum is complexed with a pterin-based molybdenum cofactor (MOCO), to form the active center of molybdenum-based enzymes. MOCO is synthesized in a four-step process involving six proteins, iron, ATP, and copper. Defects in any of the individual genes involved in this biosynthesis can result in molybdenum cofactor deficiency (MoCD). MoCD is an autosomal recessive disorder with an estimated incidence of 1 in 100,000 - 200,000 live births. Although most patients appear normal at birth, intractable seizures typically develop within hours to days of life, along with feeding difficulties, and subsequent microcephaly, brain atrophy, and severe developmental delay. Mortality is high, with a reported median survival of 2.4 to 3 years. Given the associated end-organ involvement, anesthetic management may be required during radiologic imaging or surgery procedures. We present a 6-year-old child with MoCD type A, who required anesthetic care for a magnetic expansion control (MAGEC) rod insertion with posterior spinal instrumentation under general anesthesia. End-organ involvement of MoCD is presented, previous reports of anesthetic care reviewed, and options for perioperative management discussed.
2022-08-31 | Dietary molybdenum cofactor promotes fitness by increasing Moco content and sulfite oxidase activity in the nematode C. elegans
Abstract Molybdenum cofactor (Moco) is a prosthetic group necessary for the activity of 4 unique enzymes, including the essential sulfite oxidase (SUOX-1). Moco is required for life; humans with inactivating mutations in the genes encoding Moco-biosynthetic enzymes display Moco deficiency, a rare and lethal inborn error of metabolism. Despite its importance to human health, little is known about how Moco moves among and between cells, tissues, and organisms. The prevailing view is that cells that require Moco must synthesize Moco de novo. Although, the nematode Caenorhabditis elegans appears to be an exception to this rule and has emerged as a valuable system for understanding fundamental Moco biology. C. elegans has the seemingly unique capacity to both synthesize its own Moco as well as acquire Moco from its microbial diet. However, the relative contribution of Moco from the diet or endogenous synthesis has not been rigorously evaluated or quantified biochemically. We genetically removed dietary or endogenous Moco sources in C. elegans and biochemically determined their impact on animal Moco content and SUOX-1 activity. We demonstrate that dietary Moco deficiency dramatically reduces both animal Moco content and SUOX-1 activity. Furthermore, these biochemical deficiencies have physiological consequences; we show that dietary Moco deficiency alone causes sensitivity to sulfite, the toxic substrate of SUOX-1. This work establishes the biochemical consequences of depleting dietary Moco or endogenous Moco synthesis in C. elegans and quantifies the surprising contribution of the diet to maintaining Moco homeostasis in C. elegans.
2021-02-01 | Learning from the worm: the effectiveness of protein-bound Moco to treat Moco deficiency
Molybdenum cofactor (Moco) is synthesized endogenously in humans and is essential for human development. Supplementation of Moco or its precursors has been explored as a therapy to treat Moco-deficient patients but with significant limitations. By using the nematode C. elegans as a model, Warnhoff and colleagues (pp. 212–217) describe the beneficial impact of protein-bound Moco supplementation to treat Moco deficiency. If such an effect is conserved, this advance from basic research in worms may have significant clinical implications as a novel therapy for molybdenum cofactor deficiency.
2021-01-14 | Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans.
The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a Celegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.
small molecules
2025-09-02 | Brain Magnetic Resonance Imaging of Children With Molybdenum Cofactor Deficiency.
Molybdenum cofactor deficiency (MoCD) is a rare differential diagnosis of neonatal hypoxic ischemic encephalopathy (HIE) with considerable variation in presentation and treatment outcomes. The temporospatial evolution of brain MRI appearances has not been well described. We systematically evaluated 35 MRI brain scans of 13 patients with neonatal MoCD (7 type A, 6 type B) to characterize brain abnormalities arising from exposure to toxicity related to sulfite accumulation and to evaluate changes in response to cPMP treatment in 6 children with MoCD type A. All cases showed evidence of chronic toxicity with developmental disruption. We identified a disease-specific pattern of acute and chronic brain injury, distinct from HIE. White matter edema, as the earliest sign of sulfite-related toxicity, indicates a reversible disease stage. The presence of restricted diffusion in the context of MoCD signifies irreversible brain injury and a poor neurological prognosis, irrespective of subsequent biochemical correction upon cPMP treatment. This is the largest neuroimaging study of children with MoCD and the first longitudinal study to examine MR imaging changes in MoCD type A under cPMP substitution. Neuroimaging can identify diagnostic and prognostic features with relevance for treatment decisions and for the evaluation of the effectiveness of treatment attempts.
2025-05-07 | Metformin restores mitochondrial bioenergetics and redox homeostasis through modulation of mitochondrial biogenesis and dynamics in patient derived cultured fibroblasts and an animal model of molybdenum cofactor deficiency.
Molybdenum cofactor deficiency (MoCD) is an inborn error of sulfur metabolism caused by inactivating variants in the genes encoding enzymes of the molybdenum cofactor biosynthetic pathway. Patients present with accumulation of sulfite in the brain with secondary mitochondrial bioenergetics and severe neurological manifestations. To investigate the pathophysiology of this disorder, we evaluated mitochondrial and redox homeostasis in fibroblasts derived from a patient with MoCD type A (MOCS1 deficiency) and in an animal model based on the intracerebroventricular administration of sulfite in Wistar rats. Since treatment for MoCD is largely ineffective, we also investigated the effects of metformin, an antidiabetic drug with neuroprotective potential. Reduced basal, maximal, and ATP-linked respiration and reserve respiratory capacity were verified in MOCS1 deficient fibroblasts. The protein content of MFN1/2, OPA1, DRP1, and NRF1 was also reduced, whereas p-DRP1 (Ser 637) was increased. Superoxide levels were elevated in these cells. Metformin treatment reversed these changes. Further, the p-AMPK/T-AMPK protein ratio and the expression of PRKAA1, PPARGC1A, SIRT1, DNM1L, and mitofusin 1 were increased by metformin in the deficient cells. Sulfite administration into rat brain disturbed the antioxidant defenses, and tricarboxylic acid cycle and electron transfer chain function in the striatum, cerebral cortex and cerebellum. Metformin prevented this bioenergetic dysfunction. Our findings show that metformin elicits positive effects in the brain of sulfite-treated rats and in the MOCS1 deficient cell line by modulating mitochondrial biogenesis and fission, identifying potential therapeutic intervention opportunities in MoCD.
2025-03-26 | Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate.
Molybdenum cofactor deficiency (MoCD) Type A is an ultrarare disorder causing neurodegeneration and early death. Cyclic pyranopterin monophosphate (cPMP), a molybdenum cofactor precursor, is a therapeutic option for patients with MoCD Type A. In this study, efficacy in patients with MoCD Type A treated with recombinant cPMP (rcPMP) and/or fosdenopterin, a synthetic form of cPMP, from one retrospective and two prospective open-label studies (N = 14), was compared with a retrospective/prospective natural history study (untreated; N = 37). Safety was evaluated in treated patients. Patients treated with fosdenopterin/rcPMP had significantly reduced risk of premature/early death versus untreated patients (Cox proportional hazards 5.1; 95% CI 1.32-19.36; p = 0.01). MoCD disease biomarkers of urinary S-sulfocysteine and xanthine returned to near-normal from baseline to last visit in treated patients but remained abnormal in untreated patients. At 12 months, in treated patients, 43% could sit unassisted, 44% were ambulatory, and 57% could feed orally. Initiating fosdenopterin/rcPMP treatment ≤ 14 days after birth appeared to result in better clinical outcomes than initiating > 14 days after birth. Most patients (13/14) had a treatment-emergent adverse event; most were unrelated to fosdenopterin/rcPMP, were mild to moderate in severity, and none led to treatment discontinuation. These results demonstrate that patients with MoCD Type A who received fosdenopterin/rcPMP versus untreated patients were more likely to survive. Some treated patients were able to feed orally and achieve developmental milestones including walking. Fosdenopterin/rcPMP was generally well-tolerated. Improved outcomes in patients treated early support the importance of identifying MoCD in neonates and initiating treatment as soon as possible.
2024-11-03 | cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.
We report the first, and so far, only index patient with neonatal onset MoCD type A who was diagnosed and treated early enough with cPMP to avoid severe brain injury and disability. The child presented with hypoglycemia at the age of 10 h and was diagnosed because of the incidental finding of severely decreased L-cystine in plasma. Due to a high level of awareness and excellent co-operation between metabolic laboratory and clinical services, cPMP substitution could be initiated before severe encephalopathy set in, and the child subsequently had a normal motor development. The child has been continued on daily substitution with cPMP until today (age 7 years) and has shown a satisfying long-term developmental outcome. Long-term follow-up, however, revealed significant communication difficulties and cognitive abilities in the range of mild to moderate learning disability. The severity of the metabolic disease was confirmed by the extent of biochemical abnormalities and further functional characterisation of the underlying genetic variants. This case provides further evidence that cPMP substitution does significantly alter the disease course when applied early enough. Postnatal treatment in this case was not sufficient to enable an entirely normal cognitive development, despite sustained complete normalization of the biochemical abnormalities.
2024-08-22 | Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate.
Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice.
proteins
2026-02-09 | Autism Spectrum Disorder and Long-Term Survival in Attenuated Molybdenum Cofactor Deficiency Type A: A Case Report From Saudi Arabia.
We report the case of an 18-year-old male with genetically confirmed molybdenum cofactor deficiency type A (MoCD-A) due to a homozygous pathogenic MOCS1 variant. He presented in infancy with hypotonia and developmental delay and experienced a generalized tonic seizure at 20 months of age, followed by long-term seizure remission. His clinical course was notable for preserved motor function, below-average cognitive ability, marked speech delay, autism spectrum disorder (ASD), and prominent inattentive symptoms. Metabolic testing demonstrated elevated urinary xanthine, hypoxanthine, and S-sulfocysteine levels, supporting impaired sulfite oxidase activity. Neuroimaging revealed a small, focal hypodensity in the left basal ganglia without progressive changes. This case illustrates an attenuated phenotype of MoCD-A, with survival into adulthood and detailed neuropsychiatric characterization, expanding the recognized clinical spectrum and underscoring the importance of considering metabolic etiologies in patients with overlapping developmental and behavioral features.
2025-05-05 | Perioperative Care of a Child With Molybdenum Cofactor Deficiency.
Molybdenum is a trace mineral that is a key component of several enzyme systems. In the human body, molybdenum is complexed with a pterin-based molybdenum cofactor (MOCO), to form the active center of molybdenum-based enzymes. MOCO is synthesized in a four-step process involving six proteins, iron, ATP, and copper. Defects in any of the individual genes involved in this biosynthesis can result in molybdenum cofactor deficiency (MoCD). MoCD is an autosomal recessive disorder with an estimated incidence of 1 in 100,000 - 200,000 live births. Although most patients appear normal at birth, intractable seizures typically develop within hours to days of life, along with feeding difficulties, and subsequent microcephaly, brain atrophy, and severe developmental delay. Mortality is high, with a reported median survival of 2.4 to 3 years. Given the associated end-organ involvement, anesthetic management may be required during radiologic imaging or surgery procedures. We present a 6-year-old child with MoCD type A, who required anesthetic care for a magnetic expansion control (MAGEC) rod insertion with posterior spinal instrumentation under general anesthesia. End-organ involvement of MoCD is presented, previous reports of anesthetic care reviewed, and options for perioperative management discussed.
2022-08-31 | Dietary molybdenum cofactor promotes fitness by increasing Moco content and sulfite oxidase activity in the nematode C. elegans
Abstract Molybdenum cofactor (Moco) is a prosthetic group necessary for the activity of 4 unique enzymes, including the essential sulfite oxidase (SUOX-1). Moco is required for life; humans with inactivating mutations in the genes encoding Moco-biosynthetic enzymes display Moco deficiency, a rare and lethal inborn error of metabolism. Despite its importance to human health, little is known about how Moco moves among and between cells, tissues, and organisms. The prevailing view is that cells that require Moco must synthesize Moco de novo. Although, the nematode Caenorhabditis elegans appears to be an exception to this rule and has emerged as a valuable system for understanding fundamental Moco biology. C. elegans has the seemingly unique capacity to both synthesize its own Moco as well as acquire Moco from its microbial diet. However, the relative contribution of Moco from the diet or endogenous synthesis has not been rigorously evaluated or quantified biochemically. We genetically removed dietary or endogenous Moco sources in C. elegans and biochemically determined their impact on animal Moco content and SUOX-1 activity. We demonstrate that dietary Moco deficiency dramatically reduces both animal Moco content and SUOX-1 activity. Furthermore, these biochemical deficiencies have physiological consequences; we show that dietary Moco deficiency alone causes sensitivity to sulfite, the toxic substrate of SUOX-1. This work establishes the biochemical consequences of depleting dietary Moco or endogenous Moco synthesis in C. elegans and quantifies the surprising contribution of the diet to maintaining Moco homeostasis in C. elegans.
2021-02-01 | Learning from the worm: the effectiveness of protein-bound Moco to treat Moco deficiency
Molybdenum cofactor (Moco) is synthesized endogenously in humans and is essential for human development. Supplementation of Moco or its precursors has been explored as a therapy to treat Moco-deficient patients but with significant limitations. By using the nematode C. elegans as a model, Warnhoff and colleagues (pp. 212–217) describe the beneficial impact of protein-bound Moco supplementation to treat Moco deficiency. If such an effect is conserved, this advance from basic research in worms may have significant clinical implications as a novel therapy for molybdenum cofactor deficiency.
2021-01-14 | Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans.
The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a Celegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.
small molecules
2025-09-02 | Brain Magnetic Resonance Imaging of Children With Molybdenum Cofactor Deficiency.
Molybdenum cofactor deficiency (MoCD) is a rare differential diagnosis of neonatal hypoxic ischemic encephalopathy (HIE) with considerable variation in presentation and treatment outcomes. The temporospatial evolution of brain MRI appearances has not been well described. We systematically evaluated 35 MRI brain scans of 13 patients with neonatal MoCD (7 type A, 6 type B) to characterize brain abnormalities arising from exposure to toxicity related to sulfite accumulation and to evaluate changes in response to cPMP treatment in 6 children with MoCD type A. All cases showed evidence of chronic toxicity with developmental disruption. We identified a disease-specific pattern of acute and chronic brain injury, distinct from HIE. White matter edema, as the earliest sign of sulfite-related toxicity, indicates a reversible disease stage. The presence of restricted diffusion in the context of MoCD signifies irreversible brain injury and a poor neurological prognosis, irrespective of subsequent biochemical correction upon cPMP treatment. This is the largest neuroimaging study of children with MoCD and the first longitudinal study to examine MR imaging changes in MoCD type A under cPMP substitution. Neuroimaging can identify diagnostic and prognostic features with relevance for treatment decisions and for the evaluation of the effectiveness of treatment attempts.
2025-05-07 | Metformin restores mitochondrial bioenergetics and redox homeostasis through modulation of mitochondrial biogenesis and dynamics in patient derived cultured fibroblasts and an animal model of molybdenum cofactor deficiency.
Molybdenum cofactor deficiency (MoCD) is an inborn error of sulfur metabolism caused by inactivating variants in the genes encoding enzymes of the molybdenum cofactor biosynthetic pathway. Patients present with accumulation of sulfite in the brain with secondary mitochondrial bioenergetics and severe neurological manifestations. To investigate the pathophysiology of this disorder, we evaluated mitochondrial and redox homeostasis in fibroblasts derived from a patient with MoCD type A (MOCS1 deficiency) and in an animal model based on the intracerebroventricular administration of sulfite in Wistar rats. Since treatment for MoCD is largely ineffective, we also investigated the effects of metformin, an antidiabetic drug with neuroprotective potential. Reduced basal, maximal, and ATP-linked respiration and reserve respiratory capacity were verified in MOCS1 deficient fibroblasts. The protein content of MFN1/2, OPA1, DRP1, and NRF1 was also reduced, whereas p-DRP1 (Ser 637) was increased. Superoxide levels were elevated in these cells. Metformin treatment reversed these changes. Further, the p-AMPK/T-AMPK protein ratio and the expression of PRKAA1, PPARGC1A, SIRT1, DNM1L, and mitofusin 1 were increased by metformin in the deficient cells. Sulfite administration into rat brain disturbed the antioxidant defenses, and tricarboxylic acid cycle and electron transfer chain function in the striatum, cerebral cortex and cerebellum. Metformin prevented this bioenergetic dysfunction. Our findings show that metformin elicits positive effects in the brain of sulfite-treated rats and in the MOCS1 deficient cell line by modulating mitochondrial biogenesis and fission, identifying potential therapeutic intervention opportunities in MoCD.
2025-03-26 | Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate.
Molybdenum cofactor deficiency (MoCD) Type A is an ultrarare disorder causing neurodegeneration and early death. Cyclic pyranopterin monophosphate (cPMP), a molybdenum cofactor precursor, is a therapeutic option for patients with MoCD Type A. In this study, efficacy in patients with MoCD Type A treated with recombinant cPMP (rcPMP) and/or fosdenopterin, a synthetic form of cPMP, from one retrospective and two prospective open-label studies (N = 14), was compared with a retrospective/prospective natural history study (untreated; N = 37). Safety was evaluated in treated patients. Patients treated with fosdenopterin/rcPMP had significantly reduced risk of premature/early death versus untreated patients (Cox proportional hazards 5.1; 95% CI 1.32-19.36; p = 0.01). MoCD disease biomarkers of urinary S-sulfocysteine and xanthine returned to near-normal from baseline to last visit in treated patients but remained abnormal in untreated patients. At 12 months, in treated patients, 43% could sit unassisted, 44% were ambulatory, and 57% could feed orally. Initiating fosdenopterin/rcPMP treatment ≤ 14 days after birth appeared to result in better clinical outcomes than initiating > 14 days after birth. Most patients (13/14) had a treatment-emergent adverse event; most were unrelated to fosdenopterin/rcPMP, were mild to moderate in severity, and none led to treatment discontinuation. These results demonstrate that patients with MoCD Type A who received fosdenopterin/rcPMP versus untreated patients were more likely to survive. Some treated patients were able to feed orally and achieve developmental milestones including walking. Fosdenopterin/rcPMP was generally well-tolerated. Improved outcomes in patients treated early support the importance of identifying MoCD in neonates and initiating treatment as soon as possible.
2024-11-03 | cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.
We report the first, and so far, only index patient with neonatal onset MoCD type A who was diagnosed and treated early enough with cPMP to avoid severe brain injury and disability. The child presented with hypoglycemia at the age of 10 h and was diagnosed because of the incidental finding of severely decreased L-cystine in plasma. Due to a high level of awareness and excellent co-operation between metabolic laboratory and clinical services, cPMP substitution could be initiated before severe encephalopathy set in, and the child subsequently had a normal motor development. The child has been continued on daily substitution with cPMP until today (age 7 years) and has shown a satisfying long-term developmental outcome. Long-term follow-up, however, revealed significant communication difficulties and cognitive abilities in the range of mild to moderate learning disability. The severity of the metabolic disease was confirmed by the extent of biochemical abnormalities and further functional characterisation of the underlying genetic variants. This case provides further evidence that cPMP substitution does significantly alter the disease course when applied early enough. Postnatal treatment in this case was not sufficient to enable an entirely normal cognitive development, despite sustained complete normalization of the biochemical abnormalities.
2024-08-22 | Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate.
Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice.
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Drug Discovery Landscape
2 orphan drug designations for Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, including 2 approved therapies.
2 orphan drug designations for Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Cyclic pyranopterin monophosphate [NULIBRY] | small molecules | EMA | 2010-09-20 | 2022-09-16 | TMC Pharma (EU) Limited |
fosdenopterin [Nulibry] | small molecules | FDA | 2009-11-05 | 2021-02-26 | Origin Biosciences, Inc. |
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