TY - JOUR
T1 - Timing of cerebral damage in molybdenum cofactor deficiency
T2 - A meta-analysis of case reports
AU - Ferreira, Elise A.
AU - Hofstede, Floris C.
AU - Haijes-Siepel, Hanneke A.
AU - Lichtenbelt, Klaske D.
AU - Pistorius, Lou
AU - de Sain-van der Velden, Monique G.M.
AU - Nikkels, Peter G.J.
AU - Lequin, Maarten H.
AU - de Vries, Linda S.
AU - van der Crabben, Saskia N.
AU - van Hasselt, Peter M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - Epileptic encephalopathy
KW - Meta-analysis of case reports
KW - Molybdenum cofactor deficiency
KW - Natural evolution study
KW - Sulfite oxidase deficiency
UR - http://www.scopus.com/inward/record.url?scp=85208357874&partnerID=8YFLogxK
U2 - 10.1016/j.gimo.2024.101853
DO - 10.1016/j.gimo.2024.101853
M3 - Article
AN - SCOPUS:85208357874
SN - 2949-7744
VL - 2
JO - Genetics in Medicine Open
JF - Genetics in Medicine Open
M1 - 101853
ER -