Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency.

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Mechler K, Mountford WK, Hoffmann GF, Ries M

Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency.

Genet Med. 2015 Dec;17(12):965-70. doi: 10.1038/gim.2015.12. Epub 2015 Mar 12.

PubMed ID

25764214 [ View in PubMed

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Abstract

PURPOSE: Experimental treatment with substrate replacement was successfully performed in single cases with molybdenum cofactor deficiency type A. The objective of this study was to quantitate the yet undefined natural history in untreated patients to ultimately benefit knowledge in experimental treatments in the future. METHODS: Systematic analysis of published cases with molybdenum cofactor deficiency. The main outcome measures were survival, initial cardinal disease features at onset, and diagnostic delay. RESULTS: The median survival for the overall population was 36 months. Initial cardinal disease features at onset were seizures (72%) as well as feeding difficulties (26%) and hypotonia (11%). In addition, developmental delay (9%), hemiplegia (2%), lens dislocation (2%), and hyperreflexia (1%) were reported. The median age at onset of the disease was the first day of life; the median age at diagnosis was 4.5 months. The median time to diagnosis (diagnostic delay) was 89 days. CONCLUSION: Molybdenum cofactor deficiency has its onset during the neonatal period and infancy. There is considerable diagnostic delay. Although seizures were the most frequent initial cardinal sign, molybdenum cofactor deficiency should be considered as a differential diagnosis in patients presenting with hypotonia, developmental delay, or feeding difficulties. The survival data will inform further natural-history and therapeutic studies.

DrugBank Data that Cites this Article

Drugs

Fosdenopterin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Fosdenopterin	Molybdopterin synthase catalytic subunit	Protein	Humans	Yes	Substrate	Details