Rousselot-Pailley Bérangère, Semeraro Michaela, Marquant Fabienne, Robel Laurence, Gitiaux Cyril, Kaminska Anna, Mochel Fanny, Bakouboula Prissile, Elie Caroline, Hennequin Carole, Ceballos-Picot Irène, Sanquer Sylvia, de Lonlay Pascale
Service de psychiatrie, Hôpital Universitaire Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Université Paris-Cité, CRPMS F75013, Paris, France.
J Inherit Metab Dis. 2025 Nov;48(6):e70092. doi: 10.1002/jimd.70092.
Adenylosuccinate lyase deficiency (ADSLD) is a rare neurological disorder characterized by psychomotor retardation, autistic behaviors, and seizures, with no specific treatment available. ADSL catalyzes the transformation of succinylaminoimidazole carboxamide ribotide (SAICAr) to AICAR, and succinyl-AMP (S-AMP) to AMP. The pathogenesis of the disease is primarily attributed to the toxicity of elevated SAICAr concentrations. Allopurinol, used primarily for hyperuricemia, inhibits purine synthesis and may reduce SAICAr levels. We hypothesized that administering allopurinol could decrease SAICAr levels and lead to clinical improvement. A Phase II, prospective trial evaluated the efficacy of allopurinol in patients with ADSLD over 12 months. Eight participants (four children, four young adults) with developmental delay and high SAICAr levels received Zyloric (10-20 mg/kg/day, maximum 400 mg/day for children and 900 mg/day for adults). The study assessed changes in adaptive and cognitive functioning, behavior, and urinary levels of SAICAr and succinyl-adenosine (S-Ado). Results showed clinical improvements in younger, less cognitively impaired patients, indicated by better Vineland Adaptive Behavior Scale (VABS II) scores and reduced hyperactivity on the Aberrant Behavior Checklist (ABC) and Conners Rating Scale-Revised (CRSR). These improvements correlated with significant decreases in urinary SAICAr levels and an increased S-Ado/SAICAr ratio. No changes were observed in older or noncompliant patients. Allopurinol had no effect on epilepsy but was well tolerated. Allopurinol showed behavioral and developmental benefits in younger ADSLD patients, suggesting that it may be a viable treatment option.
腺苷酸琥珀酸裂解酶缺乏症（ADSLD）是一种罕见的神经疾病，其特征为精神运动发育迟缓、自闭症行为和癫痫发作，目前尚无特效治疗方法。ADSL催化琥珀酰氨基咪唑甲酰胺核苷酸（SAICAr）转化为氨基咪唑甲酰胺核苷酸（AICAR），以及琥珀酰-AMP（S-AMP）转化为AMP。该疾病的发病机制主要归因于SAICAr浓度升高的毒性作用。主要用于治疗高尿酸血症的别嘌醇可抑制嘌呤合成，并可能降低SAICAr水平。我们推测给予别嘌醇可降低SAICAr水平并带来临床改善。一项II期前瞻性试验评估了别嘌醇在12个月内对ADSLD患者的疗效。八名发育迟缓且SAICAr水平高的参与者（四名儿童，四名青年）接受了Zyloric（10 - 20mg/kg/天，儿童最大剂量为400mg/天，成人为900mg/天）治疗。该研究评估了适应性和认知功能、行为以及尿液中SAICAr和琥珀酰腺苷（S-Ado）水平的变化。结果显示，年龄较小、认知障碍较轻的患者临床症状有所改善，表现为文兰适应行为量表（VABS II）得分更高，异常行为检查表（ABC）和修订版康纳斯评定量表（CRSR）上的多动症状减轻。这些改善与尿液中SAICAr水平显著降低以及S-Ado/SAICAr比值升高相关。年龄较大或不依从的患者未观察到变化。别嘌醇对癫痫无影响，但耐受性良好。别嘌醇对年轻的ADSLD患者显示出行为和发育方面的益处，表明它可能是一种可行的治疗选择。
