Molybdenum cofactor deficiency: A natural history.
J Inherit Metab Dis
; 45(3): 456-469, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-35192225
ABSTRACT
Molybdenum cofactor deficiency (MoCD) includes three ultrarare autosomal recessive inborn errors of metabolism (MoCD type A [MoCD-A], MoCD-B, and MoCD-C) that cause sulfite intoxication disorders. This natural history study analyzed retrospective data for 58 living or deceased patients (MoCD-A, n = 41; MoCD-B, n = 17). MoCD genotype, survival, neuroimaging, and medical history were assessed retrospectively. Prospective biomarker data were collected for 21 living MoCD patients. The primary endpoint was survival to 1 year of age in MoCD-A patients. Of the 58 MoCD patients, 49 (MoCD-A, n = 36; MoCD-B, n = 13) had first presenting symptoms by Day 28 (neonatal onset; median 2 and 4 days, respectively). One-year survival rates were 77.4% (overall), 71.8% (neonatal onset MoCD-A), and 76.9% (neonatal onset MoCD-B); median ages at death were 2.4, 2.4, and 2.2 years, respectively. The most common presenting symptoms in the overall population were seizures (60.3%) and feeding difficulties (53.4%). Sequelae included profound developmental delay, truncal hypotonia, limb hypertonia that evolved to spastic quadriplegia or diplegia, dysmorphic features, and acquired microcephaly. In MoCD-A and MoCD-B, plasma and urinary xanthine and S-sulfocysteine concentrations were high; urate remained below the normal reference range. MOCS1 mutation homozygosity was common. Six novel mutations were identified. MoCD is a severe neurodegenerative disorder that often manifests during the neonatal period with intractable seizures and feeding difficulties, with rapidly progressive significant neurologic disabilities and high 1-year mortality rates. Delineation of MoCD natural history supports evaluations of emerging replacement therapy with cPMP for MoCD-A, which may modify disease course for affected individuals.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Errores Innatos del Metabolismo de los Metales
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Metaloproteínas
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
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Newborn
Idioma:
En
Revista:
J Inherit Metab Dis
Año:
2022
Tipo del documento:
Article
País de afiliación:
Israel