Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in >80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006–2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kg•day), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989–2018) were identified by NBS and treated with natural protein restriction (1.0–1.3 g/kg•day) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973–2016) did not receive NBS or special diet. The incidence of striatal degeneration in Cohorts I, II, and III was 7%, 47%, and 90%, respectively (p < .0001). No neurologic injuries occurred after 19 months of age. Among uninjured children followed prospectively from birth (Cohort I), measures of growth, nutritional sufficiency, motor development, and cognitive function were normal. Adherence to metabolic formula and l-carnitine supplementation in Cohort I declined to 12% and 32%, respectively, by age 7 years. Cessation of strict dietary therapy altered plasma amino acid and carnitine concentrations but resulted in no serious adverse outcomes. In conclusion, neonatal diagnosis of GA1 coupled to management with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective, preventing more than 90% of striatal injuries while supporting normal growth and psychomotor development. The need for dietary interventions and emergency IV therapies beyond early childhood is uncertain.

戊二酸血症1型（GA1）是由GCDH的双等位基因突变导致的大脑有机酸代谢异常。如果不进行治疗，GA1会在两岁之前的80％以上患病儿童中引起纹状体变性。我们分析了在单一中心接受治疗的168个基因型多样的GA1患者在31年内的临床，生化和发育结局，这里将其分为三个治疗队列：队列I中的儿童（n  = 60； DOB 2006–2019）通过新生儿筛查确定（NBS），并且使用标准化的协议，其中包括一个自由赖氨酸，精氨酸富集的代谢式，肠内处理前瞻性升肉碱（100毫克/千克•天），和紧急葡萄糖，盐水，和静脉内（IV）输注升-疾病时的肉碱； NBS确定了队列II中的儿童（n = 57； DOB 1989–2018），并接受了天然蛋白质限制剂（1.0–1.3 g / kg•天）和紧急静脉输注治疗；第三代（n  = 51；出生日期1973–2016）的儿童没有接受NBS或特殊饮食。在队列I，队列II和队列III中，纹状体变性的发生率分别为7％，47％和90％（p  <.0001）。19个月大以后未发生神经系统损伤。在未受伤的儿童中，从出生开始就进行了追踪研究（队列I），其生长，营养充足，运动发育和认知功能的测量均正常。遵守代谢式和升到年龄7岁时，队列I中的补充肉毒碱分别降至12％和32％。停止严格的饮食疗法会改变血浆氨基酸和肉碱浓度，但不会导致严重的不良后果。总之，在出生后的头两年，GA1的新生儿诊断与无赖氨酸，富含精氨酸的代谢配方和紧急静脉输注的管理相结合是安全有效的，可预防超过90％的纹状体损伤，同时支持正常的生长和精神运动发展。不确定儿童早期以后是否需要饮食干预和紧急静脉治疗。