The excretion of amino acids by cystinuric patients and their relatives

Dent & Harris (1951) differentiated classical cystinuria with increased excretion of lysine and arginine from other conditions in which the urinary excretion of cystine is increased as part of a generalized amino aciduria. Harris, Mittwoch, Robson & Warren (1955) studied the genetics of the disorder and proposed that the affected families should be classified as ‘recessive ’ or ‘ incompletely recessive ’, there being no detectable abnormality in the presumably heterozygous individuals in the former group whereas the heterozygous members of the ‘incompletely recessive ’ families have detectable abnormalities in their excretion of cystine and/or the basic amino acids. Harris & Robson (1955) also concluded on the basis of genetic evidence that recessive cystinuria includes more than one genetic entity but that incompletely recessive cystinuria is genetically homogeneous. Rosenberg ‘and his colleagues classified cystinuric patients into types I, I1 and I11 on the basis of the ability of the patients’ jejunal mucosa to transport isotopically labelled amino acids in witro (Rosenberg & Segal, 1965; Rosenberg, Durant & Holland, 1965; Rosenberg, Downing, Durant & Segal, 1966). Type I cases correspond to recessive cystinuria and types I1 and I11 are subgroups of incompletely recessive cystinuria. Studies of the renal clearance of amino acids have also demonstrated heterogeneity in the disease. Thus, some patients have cystine clearance values which are signikantly greater than the simultaneously measured glomerular filtration rate, whereas in other patients the cystine clearance and glomerular filtration rate are approximately equal (Crawhall, Scowen, Thompson & Watts, 1967). Heterogeneity could be due to cystinuria including more than one patho-physiological entity which available diagnostic methods are not sufficiently sensitive to separate. Alternatively the condition might be a single genetic entity and the apparent heterogeneity might be due to different degrees of expression of the single defect. Crawhall, Saunders & Thompson (1966) studied the amino acid excretion by a small number of cystine stone formers and their parents. They concluded that arginine excretion was increased in the subjects who were homozygous for the abnormal gene causing cystinuria, but not in the corresponding heterozygotes. They also suggested that an increased lysine excretion was sometimes the only feature which differentiates cystinuria heterozygotes from normal subjects. In the present work, the excretions of cystine and the basic amino acids have been studied in cystine stone formers, their parents and in normal subjects. The cystine stone formers are regarded as being homozygous and their parents as heterozygous for the cystinuria gene. The results obtained for these three groups of subjects are compared with one another and with those obtained for the other blood relatives of the stone formers in order to determine if the members of the latter group could be classified as cystinuria homozygotes, heterozygotes or normal on * Present address : Royal Victoria Hospital, McGill University, Montreal, Canada. t Address after 1st January 1970: Medical Research Council, Clinical Research Centre, Northwick Park,