Perales-Clemente Ester, Hewitt Angela L, Studinski April L, Tillema Jan-Mendelt, Laxen William J, Oglesbee Devin, Graff Arne H, Rinaldo Piero, Lanpher Brendan C
Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA.
Department of Child Neurology Mayo Clinic Rochester Minnesota USA.
JIMD Rep. 2020 Nov 20;58(1):21-28. doi: 10.1002/jmd2.12188. eCollection 2021 Mar.
Nonaccidental trauma (NAT) is considered when pediatric patients present with intracranial injuries and a negative history of an accidental injury or concomitant medical diagnosis. The evaluation of NAT should include the consideration of possible medical causes including coagulation, hematologic, metabolic and other genetic disorders, as well as witnessed and unwitnessed accidental injuries.
We present a 7-month-old male with spells and incidental findings of bilateral subdural hematomas, retinal hemorrhages, and secondary macrocephaly, leading to investigation for NAT. Biochemical analysis showed excretion of a large amount of D-2-hydroxyglutaric in urine consistent with a biochemical diagnosis of D-2-hydroxyglutaric aciduria, a rare neurometabolic disorder characterized by developmental delay, epilepsy, hypotonia, and psychomotor retardation. None of these symptoms were present in our patient at the time of diagnosis. Molecular genetic testing revealed a pathogenic splice site variant (c.685-2A>G) and a variant of uncertain significance (c.1256G>T) with evidence of pathogenicity in the gene, consistent with a molecular diagnosis of D-2-hydroxyglutaric aciduria type I (OMIM #600721).
Since several metabolic disorders, including D-2-hydroxyglutaric aciduria type I, can present solely with symptoms suggestive of NAT (subdural and retinal hemorrhages), an early metabolic evaluation by urine organic acid analysis should be included in clinical protocols evaluating NAT. A methodical and nonjudgmental approach coordinated between pediatricians and metabolic specialists is also necessary to ensure that rare genetic conditions are not overlooked to prevent devastating social, legal, and financial consequences of suspected child abuse.
当儿科患者出现颅内损伤且意外受伤史为阴性或伴有其他医学诊断时，需考虑非意外创伤（NAT）。对NAT的评估应包括考虑可能的医学原因，包括凝血、血液学、代谢及其他遗传疾病，以及有目击和无目击的意外受伤情况。
我们报告一名7个月大的男性患儿，有发作症状，偶然发现双侧硬膜下血肿、视网膜出血及继发性巨头畸形，因此对其进行NAT调查。生化分析显示尿中大量排泄D - 2 - 羟基戊二酸，符合D - 2 - 羟基戊二酸尿症的生化诊断，这是一种罕见的神经代谢疾病，其特征为发育迟缓、癫痫、肌张力减退和精神运动发育迟缓。在诊断时，我们的患者并未出现这些症状。分子遗传学检测发现一个致病剪接位点变异（c.685 - 2A>G）和一个意义不确定的变异（c.1256G>T），该基因有致病性证据，符合I型D - 2 - 羟基戊二酸尿症（OMIM #600721）的分子诊断。
由于包括I型D - 2 - 羟基戊二酸尿症在内的几种代谢疾病可能仅表现出提示NAT的症状（硬膜下和视网膜出血），在评估NAT的临床方案中应包括通过尿有机酸分析进行早期代谢评估。儿科医生和代谢专家之间有条理且无偏见的协作方法也是必要的，以确保不忽视罕见的遗传疾病，从而防止疑似虐待儿童带来的毁灭性社会、法律和经济后果。
