193 THE USE OF ONTOGENY AND MUTATION TOGETHER TO DEFINE THREE RENAL TRANSPORT SYSTEMS FOR PROLINE AND GLYCINE IN MAN

Renal hyperiminoglycinuria with impaired net tubular reabsorption of proline (pro), hydroxyproline and glycine (gly) occurs permanently in mutant homozygotes with benign familial renal iminoglycinuria and transiently up to six mos after birth, in the normal human infant. We studied seven infants (4 Ashkenazim, 2 Fr.Can., 1 Greek) with massive iminoglycinuria detected by newborn screening. Family studies defined two types of homozygotes and one genetic compound in the group. Sequential quantitative renal clearance studies (endogenous creatinine and amino acids) under a standardized protocol were performed in the first year of life. A profound defect in net reabsorption of pro and qly was found in each proband in early infancy; fractional excretion (FE) of pro and gly approached 1.0 (no net reabsorption) in some. Mean FEpro = 0.60 and mean FEgly = 0.64 for the group in early infancy compared with normal values, < 0.05 and < 0.20 respectively. Pro reabsorption matures by 3 mos and qly reabsorption by 6 mos in normal infants; regression analysis of FEpro and FEgly vs age in the proband group revealed reabsorption capacities maturing on a delayed but analogous schedule. These findings indicate three carriers for tubular transport of pro and gly: a shared carrier for pro and gly detected by the mutation; and independent pro-preferring and gly-preferring carriers each with their own schedule of postnatal maturation. The mutant homozygous newborn lacks all three carriers at birth.