先天性代谢缺陷这个激动人心的概念,是由Garrod在本世纪初提出的,它导致了生化遗传学的诞生。他对尿黑酸尿、戊糖尿、白化病和胱氨酸尿的研究,建立了一类新的疾病,即由于某一特定酶的遗传性缺乏致使某一代谢通路的阻滞。1948年Gibson证实了这一观点,他发现隐性高铁血红蛋白血症患者,是缺乏NADH依赖性高铁血红蛋白还原酶。以后不久,Cori(1952年)发现von Gierke氏病患者缺乏葡糖-6-磷酸酶Jervis 1953年发现苯丙酮酸尿症患者缺乏苯丙氨酸羟化酸,LaDu(1956年)发现尿黑酸尿症患者,正像当初Garrod估预料的那样,缺乏尿黑酸氧化酶。到1983年为止,已发现200种以上与遗传病有关的各种酶缺乏。遗传学史上更重要的是:Garrod提出的 The exciting concept of congenital metabolic defects was raised by Garrod earlier this century, which led to the birth of biochemical genetics. His research on urinary aciduria, pentoseuria, albinism, and cystinuria created a new class of diseases in which a metabolic pathway was blocked due to the genetic deficiency of a particular enzyme. Gibson confirmed this view in 1948 and found that patients with implicit methemoglobinemia are deficient in NADH-dependent methemoglobin reductase. Shortly thereafter, Cori (1952) found that patients with von Gierke’s disease lacked glucose-6-phosphatase Jervis 1953 found phenylalanine hydroxylated acid deficiency in patients with phenylketonuria, LaDu (1956) found that urine black acid Patients with urinary disorders, as Garrod estimated, lack the urine black acid oxidase. As of 1983, more than 200 kinds of enzymes related to genetic diseases have been found to be deficient. More important in the history of genetics is: Garrod proposed