PHENOTYPES AND GENOTYPES IN CYSTINURIA

Summary Quantitative data are presented on the cystine, lysine and arginine excretion in patients with cystine stone formation and in their relatives in twenty‐five families. It is suggested that two distinct abnormal phenotypes can be differentiated. Phenotype 1 is characterized by a greatly increased excretion of cystine, lysine, arginine and ornithine. Because of the high cystine concentration in the urine cystine stone formation is fairly frequent. Phenotype 2 is characterized by a moderately increased cystine and lysine excretion, whilst the arginine and ornithine excretion is normal or only slightly raised. In this phenotype stone formation occurs only very rarely. The families fall into two groups with regard to the occurrence of phenotype 2. In one group of families phenotype 2 is not found. In these families the segregation of phenotype 1 is consistent with the hypothesis that it represents the homozygote for a rare recessive gene. This type has been called ‘recessive cystinuria’. In the other group of families phenotype 2 is frequently found. Most of the propositi are of phenotype 1. The distribution of the two abnormal phenotypes in such families is consistent with the hypothesis that phenotype 1 represents the homozygote, and phenotype 2 the heterozygote, of a rare abnormal gene. Two families have propositi of phenotype 2 who, in this instance, happen to have formed stones. These families contain no individuals of phenotype 1. Phenotype 2 again segregates in a manner which suggests that it represents the heterozygote of an abnormal gene. In all families in which phenotype 2 is found the condition has been called ‘incompletely recessive cystinuria’.