The University of Texas Medical Branch, Department of Preventive Medicine and Community Health and Internal Medicine, 301 University Boulevard, Galveston, TX 77555-1109, United States of America.
Mol Genet Metab. 2019 Nov;128(3):219-227. doi: 10.1016/j.ymgme.2019.07.002. Epub 2019 Jul 5.
Each of the four acute hepatic porphyrias is due to mutation of an enzyme in the heme biosynthetic pathway. The accumulation of pathway intermediates that occur most notably when these diseases are active is the basis for screening and establishing a biochemical diagnosis of these rare disorders. Measurement of enzyme activities and especially DNA testing also are important for diagnosis. Suspicion of the diagnosis and specific testing, particularly measurement of urinary porphobilinogen, are often delayed because the symptoms are nonspecific, even when severe. Urinary porphyrins are also measured, but their elevation is much less specific. If porphobilinogen is elevated, second line testing will establish the type of acute porphyria. DNA testing identifies the familial mutation and enables screening of family members. Management includes removal of triggering factors whenever possible. Intravenous hemin is the most effective treatment for acute attacks. Carbohydrate loading is sometimes used for mild attacks. Cyclic attacks, if frequent, can be prevented by a GnRH analogue. Frequent noncyclic attacks are sometime preventable by scheduled (e.g. weekly) hemin infusions. Long term complications may include chronic pain, renal impairment and liver cancer. Other treatments, including RNA interference, are under development.
四种急性肝卟啉症均由血红素生物合成途径中酶的突变引起。当这些疾病活跃时，途径中间产物的积累是筛查和建立这些罕见疾病生化诊断的基础。酶活性的测量，尤其是 DNA 检测，对诊断也很重要。由于症状不具特异性，甚至在严重情况下，这些疾病的诊断和具体检测（尤其是尿卟胆原的测量）常常被延迟。尿卟啉也被测量，但它们的升高特异性较差。如果卟胆原升高，则二线检测将确定急性卟啉症的类型。DNA 检测可识别家族突变，并能对家庭成员进行筛查。管理包括尽可能去除触发因素。静脉内血红素是急性发作最有效的治疗方法。碳水化合物负荷有时用于轻度发作。如果发作频繁，可以使用 GnRH 类似物预防周期性发作。如果经常非周期性发作，可以通过定期（例如每周）血红素输注来预防。长期并发症可能包括慢性疼痛、肾功能损害和肝癌。其他治疗方法，包括 RNA 干扰，正在开发中。
