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

Author:

Hitzert Marrit M.1,Bos Arend F.1,Bergman Klasien A.1,Veldman Alex2,Schwarz Guenter3,Santamaria-Araujo José Angel3,Heiner-Fokkema Rebecca4,Sival Deborah A.5,Lunsing Roelineke J.5,Arjune Sita3,Kosterink Jos G.W.6,van Spronsen Francjan J.7

Affiliation:

1. Division of Neonatology, Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands;

2. Monash Newborn, Monash Medical Centre, Department of Pediatrics and The Ritchie Centre, Monash Institute for Medical Research, Monash University, Melbourne, Australia;

3. Institute of Biochemistry, Department of Chemistry & Centre for Molecular Medicine, University of Cologne, Cologne, Germany;

4. Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands;

5. Department of Child Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands;

6. Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, the Netherlands and Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, the Netherlands;

7. Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

Molybdenum cofactor deficiency (MoCD) is a lethal autosomal recessive inborn error of metabolism with devastating neurologic manifestations. Currently, experimental treatment with cyclic pyranopterin monophosphate (cPMP) is available for patients with MoCD type A caused by a mutation in the MOCS-1 gene. Here we report the first case of an infant, prenatally diagnosed with MoCD type A, whom we started on treatment with cPMP 4 hours after birth. The most reliable method to evaluate neurologic functioning in early infancy is to assess the quality of general movements (GMs) and fidgety movements (FMs). After a brief period of seizures and cramped-synchronized GMs on the first day, our patient showed no further clinical signs of neurologic deterioration. Her quality of GMs was normal by the end of the first week. Rapid improvement of GM quality together with normal FMs at 3 months is highly predictive of normal neurologic outcome. We 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. We strongly recommend starting cPMP treatment as soon as possible after birth in infants diagnosed with MoCD type A.

Publisher

American Academy of Pediatrics (AAP)

Subject

Pediatrics, Perinatology and Child Health

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