PDF(Sci-hub)
Abstract：
BACKGROUND: 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.
METHODS: 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 D2HGDH gene, consistent with a molecular diagnosis of D-2-hydroxyglutaric aciduria type I (OMIM #600721).
CONCLUSIONS: 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.
METHODS: 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 D2HGDH gene, consistent with a molecular diagnosis of D-2-hydroxyglutaric aciduria type I (OMIM #600721).
CONCLUSIONS: 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.
摘要：
■当儿科患者出现颅内损伤和意外损伤或伴随医学诊断的阴性病史时，考虑非意外创伤（NAT）。NAT的评估应包括考虑可能的医疗原因，包括凝血，血液学，代谢和其他遗传疾病，以及目击和目击意外伤害。
■我们介绍了一名7个月大的男性，他有双侧硬膜下血肿的法术和偶然发现，视网膜出血,和继发性大头畸形，导致对NAT的调查。生化分析显示尿液中大量D-2-羟基戊二酸的排泄与D-2-羟基戊二酸尿症的生化诊断一致，一种以发育迟缓为特征的罕见神经代谢紊乱,癫痫,低张力,和精神运动迟钝.在诊断时，我们的患者均未出现这些症状。分子遗传学检测揭示了致病性剪接位点变异（c.685-2A>G）和不确定意义的变异（c.1256G>T），在D2HGDH基因中具有致病性，与I型D-2-羟基戊二酸尿症的分子诊断一致（OMIM#600721）。
■由于几种代谢紊乱，包括D-2-羟基戊二酸尿症I型，只能表现为NAT（硬膜下和视网膜出血）的症状，通过尿液有机酸分析进行早期代谢评估应纳入评估NAT的临床方案.儿科医生和代谢专家之间协调的有条理和非判断的方法也是必要的，以确保不忽视罕见的遗传条件，以防止破坏性的社会，legal,以及涉嫌虐待儿童的经济后果。
■我们介绍了一名7个月大的男性，他有双侧硬膜下血肿的法术和偶然发现，视网膜出血,和继发性大头畸形，导致对NAT的调查。生化分析显示尿液中大量D-2-羟基戊二酸的排泄与D-2-羟基戊二酸尿症的生化诊断一致，一种以发育迟缓为特征的罕见神经代谢紊乱,癫痫,低张力,和精神运动迟钝.在诊断时，我们的患者均未出现这些症状。分子遗传学检测揭示了致病性剪接位点变异（c.685-2A>G）和不确定意义的变异（c.1256G>T），在D2HGDH基因中具有致病性，与I型D-2-羟基戊二酸尿症的分子诊断一致（OMIM#600721）。
■由于几种代谢紊乱，包括D-2-羟基戊二酸尿症I型，只能表现为NAT（硬膜下和视网膜出血）的症状，通过尿液有机酸分析进行早期代谢评估应纳入评估NAT的临床方案.儿科医生和代谢专家之间协调的有条理和非判断的方法也是必要的，以确保不忽视罕见的遗传条件，以防止破坏性的社会，legal,以及涉嫌虐待儿童的经济后果。
