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Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports
Elise A Ferreira1,2, Floris C Hofstede3, Hanneke A Haijes-Siepel3
1Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Purpose:
Molybdenum cofactor deficiency (MoCD) classically presents shortly after birth, with neurological symptoms ascribed to postnatal toxicity of accumulating sulphite. Case reports suggest that cerebral damage associated with MoCD may have a prenatal onset.
Methods:
A meta-analysis of case reports was performed on individuals with genetically proven MoCD retrieved through a systematic review and in-house search. Cases were categorized as classical or late-onset, based on the time of onset of symptoms. Available cerebral images were scored for the presence of restricted diffusion, pathological signal, subcortical cysts, and atrophy. Estimated onset of each event and the minimal number of events needed to explain the observed imaging abnormalities were deduced by combining age at imaging, type of imaging abnormality, and known natural evolution of the imaging abnormalities.
Results:
Of a total of 30 retrieved cases, 21 were classical. Prenatal origin of damage was possible in all classical cases and certain in 11 of 21 (52%). Multiple events were deduced in 5/21 classical cases based on imaging data alone and in 11 of 21 cases when presuming that a postnatal onset of symptoms signifies a recent event. Multiple, but postnatal, events were also described in 3 of 9 late-onset cases.
Conclusion:
Prenatal onset of cerebral damage in patients with classical MoCD is more frequently encountered than anticipated. It may have been overlooked by the overwhelming postnatal symptoms erroneously pointing to a single culprit. This insight is important when counseling for prognosis, particularly in the context of considering the timing and anticipated prospects of therapeutic intervention.
Insights
Molybdenum cofactor deficiency (MoCD) brain damage often begins before birth, not just after birth as previously thought. This prenatal onset impacts prognosis and treatment timing for affected infants.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Molybdenum cofactor deficiency (MoCD) classically presents with neurological symptoms after birth, attributed to sulphite toxicity.
- However, case reports suggest that cerebral damage in MoCD might originate prenatally.
Purpose of the Study:
- To investigate the potential prenatal onset of cerebral damage in molybdenum cofactor deficiency (MoCD).
- To analyze imaging findings and determine the timing of neurological events in MoCD patients.
Main Methods:
- A meta-analysis of genetically confirmed MoCD cases was conducted.
- Cerebral images were scored for abnormalities, and the onset of damage was estimated based on imaging data and clinical presentation.
Main Results:
- Prenatal damage was possible in all classical MoCD cases and confirmed in 52% (11/21).
- Multiple neurological events were deduced in classical cases, with some potentially occurring prenatally.
- Late-onset MoCD cases also showed evidence of multiple, postnatal events.
Conclusions:
- Prenatal onset of cerebral damage is common in classical MoCD and may be underestimated.
- Recognizing prenatal damage is crucial for accurate prognosis and guiding therapeutic interventions.
- This finding challenges the traditional view of MoCD's postnatal-exclusive neurological impact.
