Biochemical Genetics and Newborn Screening, The Children's Hospital at Westmead, Westmead, NSW, Australia.
J Inherit Metab Dis. 2010 Oct;33(5):501-6. doi: 10.1007/s10545-009-9001-1. Epub 2010 Jan 5.
Assessing the outcome of fatty acid oxidation disorders is difficult, as most are rare. For diagnosis by newborn screening, the situation is compounded: far more cases are diagnosed by screening than by clinical presentation, representing a somewhat different cohort. The literature on outcome was reviewed. For disorders other than medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency there was insufficient evidence to make many firm statements. In MCAD deficiency, risk of death in the first 72 h is around 4%, with a further approximately 5-7% fatality rate in the first 6 years but very low subsequent risk in previously undiagnosed patients. The risk of death after diagnosis is very low at any age, with good management. The long-term outcome is good nowadays. Very-long-chain acyl-CoA dehydrogenase deficiency poses a risk of death in early infancy, but the condition is generally treatable, with a good outcome after diagnosis. Approximately 10-20% of patients diagnosed by newborn screening and treated nevertheless suffer episodic rhabdomyolysis. Some patients never become symptomatic. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is treatable, but most patients suffer episodic hypoketotic hypoglycaemia and rhabdomyolysis. Generalised mitochondrial tri-functional protein deficiency has high early mortality rate. A more insidious presentation also occurs, with symptoms sometimes confined to progressive axonal neuropathy. Among carnitine cycle disorders, carnitine transporter deficiency, potentially lethal, is uniformly successfully treated orally with carnitine. Carnitine-acylcarnitine translocase and early-onset carnitine palmitoyl transferase type II (CPT II) deficiencies have an extremely high neonatal mortality rate. Late-onset CPT II is characterised only by episodic rhabdomyolysis on severe exercise. CPT type IA deficiency may often be benign, although early presentation with hypoketotic hypoglycaemia certainly occurs.
评估脂肪酸氧化障碍的预后较为困难，因为大多数此类疾病都较为罕见。对于新生儿筛查诊断而言，情况则更为复杂：通过筛查诊断出的病例远远多于临床表现诊断的病例，这代表着一个略有不同的患者群体。我们对相关文献进行了回顾。对于除中链酰基辅酶 A 脱氢酶（MCAD）缺乏症以外的其他疾病，由于缺乏足够的证据，我们无法做出很多明确的结论。在 MCAD 缺乏症中，前 72 小时内的死亡风险约为 4%，前 6 年内还会有另外约 5-7%的死亡率，但对于之前未诊断的患者，后续风险非常低。在任何年龄，经良好治疗后，死亡风险都非常低。极长链酰基辅酶 A 脱氢酶缺乏症会增加婴儿早期死亡的风险，但这种疾病通常可以治疗，且在诊断后具有良好的预后。大约 10-20%通过新生儿筛查诊断并接受治疗的患者仍会出现间歇性横纹肌溶解。有些患者从未出现过症状。单纯性长链 3-羟酰基辅酶 A 脱氢酶缺乏症可治疗，但大多数患者会间歇性出现低酮性低血糖和横纹肌溶解。全面性线粒体三功能蛋白缺乏症早期死亡率高。此外，还存在一种更为隐匿的发病模式，其症状有时仅局限于进行性轴索性神经病。在肉碱循环障碍中，肉碱转运蛋白缺乏症具有致命风险，经口服肉碱治疗可得到有效控制。肉碱酰基辅酶 A 转移酶和早发性肉碱棕榈酰基转移酶 II（CPT II）缺乏症的新生儿死亡率极高。迟发性 CPT II 仅表现为剧烈运动时间歇性横纹肌溶解。CPT Ⅰ A 缺乏症可能通常良性，但也会出现低酮性低血糖等早期表现。
