Zübarioğlu Tanyel, Kıykım Ertuğrul, Aktuğlu-Zeybek Çiğdem
Division of Nutrition and Metabolism, Department of Pediatrics, İstanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, İstanbul, Turkey.
Turk Arch Pediatr. 2023 Jan;58(1):3-9. doi: 10.5152/TurkArchPediatr.2022.22301.
Porphyrias are inborn errors of heme biosynthesis pathway that result in neurovisceral and/ or cutaneous manifestations which occur with episodic attacks, usually accompanied by a multisystemic involvement. Acute hepatic porphyrias include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficiency porphyria. Acute hepatic porphyrias may present with symptoms of an affected central, peripheral, and autonomic nervous system and are generally diagnosed in time of an acute neurovisceral attack. In children, clinical picture is more complicated and presents with neurological findings predominantly. First-line investigation should be the urinary porphobilinogen and aminolevulinic acid performance when acute hepatic porphyria is clinically suspected. Comprehensive testing including urine porphyrin separation, fluorescence scanning of diluted plasma at neutral pH, evaluation of fecal porphyrins, and measurement of erythrocyte porphobilinogen deaminase activity is indicated for confirmation or exclusion of the porphyria and define the type of acute hepatic porphyrias. The main aim of the treatment is to decrease aminolevulinic acid, porphobilinogen, and porphyrins by reducing hepatic ALAS1 activity. The first measure should always be the avoidance of any porphyrinogenic drugs. Hemin therapy should not be delayed in the treatment of a severe acute attack. Gonadotropin-releasing hormone analogs and prophylactic hemin protocols can be used for selected cases with more than 4 attacks per year. Givosiran is a promising treatment option for severe cases.
卟啉病是血红素生物合成途径的先天性缺陷，可导致神经内脏和/或皮肤表现，通常以发作性发作的形式出现，常伴有多系统受累。急性肝卟啉病包括急性间歇性卟啉病、混合型卟啉病、遗传性粪卟啉病和氨基乙酰丙酸脱水酶缺乏性卟啉病。急性肝卟啉病可能表现为中枢、外周和自主神经系统受累的症状，通常在急性神经内脏发作时被诊断出来。在儿童中，临床表现更为复杂，主要表现为神经系统症状。当临床怀疑急性肝卟啉病时，一线检查应是检测尿卟胆原和氨基乙酰丙酸。为了确诊或排除卟啉病并确定急性肝卟啉病的类型，需要进行包括尿卟啉分离、中性pH值下稀释血浆的荧光扫描、粪便卟啉评估以及红细胞卟胆原脱氨酶活性测定在内的综合检测。治疗的主要目的是通过降低肝脏δ-氨基-γ-酮戊酸合成酶1（ALAS1）的活性来减少氨基乙酰丙酸、卟胆原和卟啉。首要措施始终是避免使用任何可诱发卟啉生成的药物。在治疗严重急性发作时，不应延迟使用血红素疗法。促性腺激素释放激素类似物和预防性血红素方案可用于每年发作超过4次的特定病例。吉沃西兰（Givosiran）是治疗严重病例的一种有前景的选择。
