Molybdenum cofactor deficiency: A natural history
Ronen Spiegel1,2, Bernd C Schwahn3,4, Liza Squires5
1Emek Medical Center, Afula, Israel.
Journal of Inherited Metabolic Disease
|February 22, 2022
Summary
Molybdenum cofactor deficiency (MoCD) is a severe metabolic disorder causing early-onset seizures and feeding issues. This study highlights high mortality rates and progressive neurological damage, supporting new treatment evaluations.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Molybdenum cofactor deficiency (MoCD) comprises three ultrarare autosomal recessive inborn errors of metabolism.
- These disorders lead to sulfite intoxication, causing severe neurological impairment.
- Understanding the natural history of MoCD is crucial for evaluating therapeutic interventions.
Purpose of the Study:
- To analyze the natural history of Molybdenum cofactor deficiency (MoCD) types A and B.
- To assess genotype, survival rates, neuroimaging, and clinical presentation in MoCD patients.
- To provide data supporting the evaluation of emerging therapies like cPMP for MoCD-A.
Main Methods:
- Retrospective analysis of data from 58 living or deceased MoCD patients (MoCD-A, n=41; MoCD-B, n=17).
- Assessment of MoCD genotype, survival, neuroimaging, and medical history.
- Prospective collection of biomarker data for 21 living MoCD patients.
Main Results:
- 49 out of 58 patients (84.5%) presented with neonatal onset (by Day 28).
- One-year survival rates were 77.4% overall, 71.8% for neonatal MoCD-A, and 76.9% for neonatal MoCD-B.
- Common symptoms included seizures (60.3%) and feeding difficulties (53.4%), leading to severe neurodevelopmental sequelae and high mortality.
Conclusions:
- MoCD is a severe, often neonatal-onset neurodegenerative disorder with significant mortality and progressive disabilities.
- Biomarker analysis revealed elevated xanthine and S-sulfocysteine, with low urate levels.
- Natural history data supports the evaluation of cPMP replacement therapy for MoCD-A to potentially alter disease progression.
Keywords:
molybdenum cofactor deficiencynatural history studyneurodegenerative disordersulfite intoxication syndromesulfite oxidase deficiencyMore Related Videos
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