Lindberg R L, Porcher C, Grandchamp B, Ledermann B, Bürki K, Brandner S, Aguzzi A, Meyer U A
Department of Pharmacology, University of Basel, Switzerland.
Nat Genet. 1996 Feb;12(2):195-9. doi: 10.1038/ng0296-195.
Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients. The clinical expression of the disease is characterized by acute, life-threatening attacks of 'porphyric neuropathy' that include abdominal pain, motor and sensory neurological deficits and psychiatric symptoms. Attacks are frequently precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms of AIP we have generated Pbgd-deficient mice by gene targeting. These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioural tests reveal decreased motor function and histopathological findings include axonal neuropathy and neurologic muscle atrophy.
急性间歇性卟啉病（AIP）是一种人类疾病，由血红素生物合成酶——胆色素原脱氨酶（PBGD）的显性遗传部分缺陷引起。在大多数人群中，AIP性状的发生率为1/10000，但在精神病患者中可能明显更高（1/500）。该疾病的临床表型特征为“卟啉性神经病变”的急性、危及生命的发作，包括腹痛、运动和感觉神经功能缺损以及精神症状。发作常由药物、酒精和低热量摄入诱发。其他肝性卟啉病也会出现相同症状。为了研究AIP神经症状的发病机制，我们通过基因靶向技术培育出了Pbgd缺陷小鼠。这些小鼠表现出人类AIP的典型生化特征，特别是肝Pbgd活性降低、δ-氨基乙酰丙酸合酶活性增加，以及在用苯巴比妥等药物治疗后，血红素前体δ-氨基乙酰丙酸的尿排泄量大幅增加。行为测试显示运动功能下降，组织病理学结果包括轴索性神经病变和神经性肌肉萎缩。
