Ontogeny of amino acid reabsorption in human kidney. Evidence from the homozygous infant with familial renal iminoglycinuria for multiple proline and glycine systems

Pediatr Res. 1979 Jan;13(1):65-70. doi: 10.1203/00006450-197901000-00014.

Abstract

Seven infants (two French Canadian, four Ashkenazi Jewish, and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening in the second week of life. Follow-up investigations and family studies revealed that each subject had a benign condition, familial renal iminoglycinuria, an autosomal recessive condition. The family studies (Table 1 and Fig. 1) indicate the presence of at least two different mutant alleles segregating in this small group of probands. Hmozygotes of two forms and one genetic compound were identified. Quantitative studies revealed normal concentrations of proline and glycine in plasma (Fig. 2), normal maturation of creatinine clearance (as an index of glomerular filtration rate) (Fig. 3), and elevated renal clearance of proline and glycine (Table 2). Fractional excretion (CAA/CCR) of both proline and glycine in the probands was far in excess of that expected for the normal postnatal infant; FFPro and FEGly approached 100% of the filtered load on occasion (Fig. 4). A schedule of maturing tubular reabsorptive activity was apparent in the proband group. Proline reabsorption matured earlier than glycine reabsorption in the homozygotes (and the genetic compound) as it does in the normal infants (Fig. 5). Our findings suggest that three gene products serve net tubular reabsorption of imino acids and glycine in human kidney. One, affected by mutation in our patients, is responsible for a shared transport activity; a second with preference for proline, and not affected by the mutation, has an "early" schedule of postnatal maturation; and a third with preference for glycine, also not affected by the mutation, has a "late" schedule of maturation.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acids / metabolism*
  • Glycine / metabolism
  • Humans
  • Imino Acids / urine*
  • Infant, Newborn
  • Kidney Tubules / metabolism
  • Mutation
  • Proline / metabolism
  • Renal Tubular Transport, Inborn Errors / genetics*
  • Syndrome

Substances

  • Amino Acids
  • Imino Acids
  • Proline
  • Glycine