Akagi Reiko, Inoue Rikako, Muranaka Shikibu, Tahara Tsuyoshi, Taketani Shigeru, Anderson Karl E, Phillips John D, Sassa Shigeru
Okayama Prefectural University, Japan.
Br J Haematol. 2006 Jan;132(2):237-43. doi: 10.1111/j.1365-2141.2005.05852.x.
Summary A Caucasian male had symptoms of acute porphyria, with increases in urinary delta-aminolaevulinic acid (ALA), porphobilinogen (PBG) and coproporphyrin that were consistent with hereditary coproporphyria (HCP). However, a greater than expected increase in ALA, compared with PBG, and a substantial increase in erythrocyte zinc protoporphyrin, suggested additional ALA dehydratase (ALAD) deficiency. Nucleotide sequence analysis of coproporphyrinogen oxidase (CPO) cDNA of the patient, but not of the parents, revealed a novel nucleotide transition G835-->C, resulting in an amino acid change, G279R. The mutant CPO protein expressed in Escherichia coli was unstable, and produced about 5% of activity compared with the wild-type CPO. Erythrocyte ALAD activity was 32% of normal in the proband. Nucleotide sequence analysis of cloned ALAD cDNAs from the patient revealed a C36-->G base transition (F12L amino acid change). The F12L ALAD mutation, which was found in the mother and a brother, was previously described, and is known to lack any enzyme activity. This patient thus represents the first case of porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level.
摘要 一名白种男性有急性卟啉病症状，尿中δ-氨基-γ-酮戊酸（ALA）、卟胆原（PBG）和粪卟啉增加，与遗传性粪卟啉病（HCP）相符。然而，与PBG相比，ALA的增加高于预期，且红细胞锌原卟啉大幅增加，提示存在额外的ALA脱水酶（ALAD）缺乏。对患者而非其父母的粪卟啉原氧化酶（CPO）cDNA进行核苷酸序列分析，发现一个新的核苷酸转换G835→C，导致氨基酸变化G279R。在大肠杆菌中表达的突变CPO蛋白不稳定，与野生型CPO相比，其活性约为5%。先证者红细胞ALAD活性为正常的32%。对患者克隆的ALAD cDNA进行核苷酸序列分析，发现一个C36→G碱基转换（F12L氨基酸变化）。在母亲和一个兄弟中发现的F12L ALAD突变先前已有描述，已知其缺乏任何酶活性。因此，该患者代表了首例在分子水平上同时证实存在CPO和ALAD缺乏的卟啉病病例。
