通过快速全基因组测序诊断产前发病致死性腺苷酸琥珀酸裂解酶缺乏症：病例报告
Prenatal-Onset Lethal Adenylosuccinate Lyase Deficiency Diagnosed by Rapid Whole Genome Sequencing: A Case Report.
摘要(中文译文)
腺苷酸琥珀酸裂解酶缺乏症（ADSLD）是一种超罕见的常染色体隐性遗传性嘌呤代谢障碍。最严重的新生儿表型表现为自出生即出现的重度脑病、肌张力低下、呼吸功能不全及早期癫痫发作。一名胎龄34+0周的早产儿出生，产前即发现进行性小头畸形及轻度羊水过多。出生时，该新生儿无自主呼吸且肌张力显著低下，需行通气及气管插管。呼吸窘迫综合征（RDS）经肺表面活性物质治疗，但两次拔管尝试使用无创持续气道正压/双相气道正压（nCPAP/DuoPAP）均未成功。神经系统方面，患儿表现为重度中枢性肌张力低下、刺激诱发性肌阵挛，振幅整合脑电图（aEEG）显示爆发-抑制模式。遂启动苯巴比妥及左乙拉西坦抗癫痫治疗。脑磁共振成像（MRI）显示小头畸形伴脑回简化、双侧脑室内出血（IVH）并附加后颅窝出血、髓鞘化延迟及进展性出血后脑积水。靶向生化检测发现尿液及血清中琥珀酰嘌呤（琥珀酰腺苷（S-Ado）及SAICA-核糖苷（SAICAr））显著升高。快速全基因组测序（WGS）证实为常染色体隐性ADSLD。鉴于缺乏疾病修饰治疗且预后极差，治疗转为以舒适为导向的姑息疗护。对于表现为重度小头畸形、重度肌张力低下及早期癫痫性脑病的新生儿，应考虑ADSLD。在条件允许且临床适宜时，快速基因组检测可能有助于及时明确病因学诊断，为预后判断及共同决策提供支持。
Abstract
Adenylosuccinate lyase deficiency (ADSLD) is an ultra-rare autosomal recessive disorder of purine metabolism. The most severe neonatal phenotype presents with profound encephalopathy from birth, hypotonia, respiratory insufficiency, and early seizures. A preterm infant was delivered at 34+0 weeks with antenatal progressive microcephaly and mild polyhydramnios. At birth, the neonate exhibited absent spontaneous respiration and marked hypotonia, necessitating ventilation and intubation. Respiratory distress syndrome (RDS) was managed with surfactant, but two extubation attempts with non-invasive continuous positive airway pressure/biphasic positive airway pressure (nCPAP/DuoPAP) were unsuccessful. Neurologically, the infant demonstrated profound central hypotonia, stimulus-induced myoclonus, and a burst-suppression pattern on amplitude-integrated electroencephalography (aEEG). Antiseizure therapy with phenobarbital and levetiracetam was initiated. Brain magnetic resonance imaging (MRI) revealed microcephaly with simplified gyrification, bilateral intraventricular hemorrhage (IVH) with additional posterior fossa hemorrhage, delayed myelination, and evolving post-hemorrhagic hydrocephalus. Targeted biochemical testing identified markedly elevated succinylpurines (succinyladenosine (S-Ado) and SAICA-riboside (SAICAr)) in urine and serum. Rapid whole-genome sequencing (WGS) confirmed autosomal recessive ADSLD. In the absence of disease-modifying therapy and given the extremely poor prognosis, care was transitioned to comfort-focused palliation. ADSLD should be considered in neonates presenting with severe microcephaly, profound hypotonia, and early epileptic encephalopathy. Rapid genomic testing, when available and clinically appropriate, may enable timely etiologic diagnosis, supporting prognostication and shared decision-making.
如何引用
AMA
Jiri Dusek, Lenka Nedvedova, Eva Rysava, Josef Bartl, Petra Pokorna, Katerina Slaba. Prenatal-Onset Lethal Adenylosuccinate Lyase Deficiency Diagnosed by Rapid Whole Genome Sequencing: A Case Report.. Cureus. 2026; doi:10.7759/cureus.109493.
APA
Jiri Dusek, Lenka Nedvedova, Eva Rysava, Josef Bartl, Petra Pokorna, Katerina Slaba (2026). Prenatal-Onset Lethal Adenylosuccinate Lyase Deficiency Diagnosed by Rapid Whole Genome Sequencing: A Case Report.. Cureus. https://doi.org/10.7759/cureus.109493
GB/T 7714
Jiri Dusek, Lenka Nedvedova, Eva Rysava, Josef Bartl, Petra Pokorna, Katerina Slaba. Prenatal-Onset Lethal Adenylosuccinate Lyase Deficiency Diagnosed by Rapid Whole Genome Sequencing: A Case Report.[J]. Cureus, 2026 doi:10.7759/cureus.109493.
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