Ali M, Rosien U, Cox T M
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, U.K.
Q J Med. 1993 Jan;86(1):25-30.
Hereditary fructose intolerance is a recessively-transmitted disorder of metabolism caused by deficiency of aldolase B in the liver, intestine and kidney, that responds favourably to an exclusion diet. The occurrence of fatal hepatorenal failure in a 16-year-old girl, who had received infusions of fructose and sorbitol during minor surgery, led us to suspect that she had suffered from hereditary fructose intolerance. Molecular analysis of leucocyte DNA obtained from her brother who had had a long-standing aversion to fruit and sugar, showed two previously unknown mutations in the aldolase B gene. An initiation codon mutation, M-1T, was inherited from the father, whereas Y203X, inherited from the mother, is a nonsense mutation that replaces a tyrosine codon by the ochre termination signal. The only source of genomic DNA from the index case was a fixed fragment of necrotic liver that had been obtained by needle aspiration postmortem and was embedded in paraffin wax. Analysis of aldolase B genes in this sample by procedures based on the polymerase chain reaction (PCR) confirmed the presence of both mutations in the proposita, the diagnosis of hereditary fructose intolerance, and the cause of death.
遗传性果糖不耐受是一种隐性遗传的代谢紊乱疾病，由肝脏、肠道和肾脏中醛缩酶B缺乏引起，对排除果糖饮食反应良好。一名16岁女孩在小手术期间接受了果糖和山梨醇输注后发生致命性肝肾衰竭，这使我们怀疑她患有遗传性果糖不耐受。对其长期厌恶水果和糖的哥哥的白细胞DNA进行分子分析，发现醛缩酶B基因有两个以前未知的突变。起始密码子突变M-1T来自父亲，而来自母亲的Y203X是一种无义突变，用赭石终止信号取代了酪氨酸密码子。索引病例的基因组DNA唯一来源是死后经针吸获得并石蜡包埋的坏死肝固定切片。通过基于聚合酶链反应（PCR）的方法对该样本中的醛缩酶B基因进行分析，证实先证者存在这两种突变，确诊为遗传性果糖不耐受，并明确了死因。
