Bijarnia S, Wiley V, Carpenter K, Christodoulou J, Ellaway C J, Wilcken B
Genetic Metabolic Disorders Service, The Children's Hospital at Westmead, Sydney, NSW, Australia.
J Inherit Metab Dis. 2008 Aug;31(4):503-7. doi: 10.1007/s10545-008-0912-z. Epub 2008 Aug 9.
Glutaric aciduria type I (GA I), a cerebral organic acidaemia with the potential for severe neurological consequences, can now be detected by tandem mass spectrometry newborn screening. Early detection with implementation of careful management strategies appears to lessen the likelihood of neurological damage. We assessed the outcome in all 10 GA I patients detected in New South Wales during the last decade. Three patients were detected clinically and 7 by newborn screening. Diagnosis was confirmed by detection of significantly elevated urinary 3-hydroxybutyrate and glutarate in urine, isolated elevation of glutarylcarnitine in plasma, typical clinical and MRI findings in several, and mutation analysis or enzyme analysis on cultured skin fibroblasts in 4 cases. The birth frequency was 1:90,000. Following diagnosis, treatment was initiated in all children with oral carnitine (100 mg/kg per day) and a low-protein diet supplemented with a lysine-free, low-tryptophan amino acid formula. Disability was assessed in fields of motor, cognitive and speech development and scored according to Kyllerman. Clinically diagnosed patients were all symptomatic, with severity scores (out of 9) of 3, 5 and 9. Six of seven patients detected by newborn screening are asymptomatic, 4 being aged 2-6 years. One patient had a severe decompensation at 7 months, despite full management advice and treatment, and later died. Our data support previous findings that early diagnosis reduces neurological complications, but show that even with early diagnosis and careful management severe complications may ensue in some.
I型戊二酸血症（GA I）是一种可导致严重神经后果的脑性有机酸血症，现在可通过串联质谱新生儿筛查检测出来。早期检测并实施谨慎的管理策略似乎可降低神经损伤的可能性。我们评估了新南威尔士州在过去十年中检测出的所有10例GA I患者的预后情况。3例患者为临床诊断，7例通过新生儿筛查发现。通过检测尿中3-羟基丁酸和戊二酸显著升高、血浆中戊二酰肉碱单独升高、部分患者典型的临床和MRI表现以及4例患者培养的皮肤成纤维细胞的突变分析或酶分析来确诊。发病率为1:90,000。确诊后，所有儿童均开始接受治疗，口服肉碱（每天100 mg/kg）并采用低蛋白饮食，补充不含赖氨酸、低色氨酸的氨基酸配方奶粉。根据运动、认知和语言发育领域评估残疾情况，并按照Kyllerman评分。临床诊断的患者均有症状，严重程度评分（满分9分）分别为3分、5分和9分。通过新生儿筛查发现的7例患者中有6例无症状，其中4例年龄在2至6岁之间。1例患者尽管接受了全面的管理建议和治疗，但在7个月时出现严重失代偿，随后死亡。我们的数据支持了先前的研究结果，即早期诊断可减少神经并发症，但也表明即使早期诊断并谨慎管理，仍有部分患者可能会出现严重并发症。
