Ferreira Elise A, Hofstede Floris C, Haijes-Siepel Hanneke A, Lichtenbelt Klaske D, Pistorius Lou, de Sain-van der Velden Monique G M, Nikkels Peter G J, Lequin Maarten H, de Vries Linda S, van der Crabben Saskia N, van Hasselt Peter M
Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
United for Metabolic Diseases (UMD), The Netherlands.
Genet Med Open. 2024 May 24;2:101853. doi: 10.1016/j.gimo.2024.101853. eCollection 2024.
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.
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.
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.
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.
钼辅因子缺乏症（MoCD）通常在出生后不久出现，其神经症状归因于累积亚硫酸盐的产后毒性。病例报告表明，与MoCD相关的脑损伤可能在产前就已开始。
对通过系统评价和内部检索获得的基因确诊为MoCD的个体的病例报告进行荟萃分析。根据症状出现时间，将病例分为典型或迟发性。对可用的脑部图像进行评分，以确定是否存在扩散受限、病理信号、皮质下囊肿和萎缩。通过结合成像时的年龄、成像异常类型和成像异常的已知自然演变，推断每个事件的估计发病时间以及解释观察到的成像异常所需的最少事件数。
在总共检索到的30例病例中，21例为典型病例。所有典型病例的损伤都有可能起源于产前，21例中有11例（52%）确定为产前起源。仅根据成像数据，21例典型病例中有5例推断出多个事件；当假定症状产后出现表示最近发生的事件时，21例中有11例推断出多个事件。9例迟发性病例中有3例也描述了多个但为产后的事件。
典型MoCD患者脑损伤的产前发病比预期更常见。它可能被压倒性的产后症状所忽视，这些症状错误地指向单一罪魁祸首。这一见解在咨询预后时很重要，特别是在考虑治疗干预的时机和预期前景的背景下。
