The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of ... The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070).
De Vries et al. (1957) found hyperglycinuria in a grandmother, her daughter, and 2 granddaughters in an Ashkenazi Jewish kindred. The grandmother had had renal colic, and renal oxalate stones were demonstrated in the 2 granddaughters. This family ... De Vries et al. (1957) found hyperglycinuria in a grandmother, her daughter, and 2 granddaughters in an Ashkenazi Jewish kindred. The grandmother had had renal colic, and renal oxalate stones were demonstrated in the 2 granddaughters. This family is apparently unique for the association of oxalate stones. It was plausibly suggested by Scriver (1968) that the glycinuria trait observed in these families was the heterozygous state of iminoglycinuria (242600), a disorder that had been described several times in Ashkenazi families (Tancredi et al., 1970). Adams and Nance (1967) described a brother and sister with paroxysmal tachycardia, hypertension, syncope and seizures, associated with dominantly inherited microphthalmia, cataracts, hyperglycinuria, and renal stones. A disturbance in glycine metabolism was postulated. Greene et al. (1973) reported an Ashkenazi family in which the father and 2 sons had hyperglycinuria. The proband was discovered when he was studied as a normal volunteer. The father had a history compatible with renal colic but had not been known to pass stones. One son had a lifelong impairment of the sense of smell. Plasma glycine concentrations were normal. Intravenous proline infusion in 1 son showed a normal maximal transport rate for proline, but there was marked splay in the renal tubular titration curve for proline reabsorption, considered consistent with a 'Km' mutation affecting proline binding. Greene et al. (1973) concluded that the mutation affecting glycine-proline-hydroxyproline renal transport in their family is different from that in previously described families. They suggested the designation iminoglycinuria type II. Broer et al. (2008) noted that the physiologic measurements reported by Greene et al. (1973) accurately described their own functional analysis of the SLC36A2 G87V mutation (608331.0001), which has the same maximum velocity but a change in affinity for proline compared to wildtype.
Broer et al. (2008) studied 3 French Canadian and 4 Australian families, each with an index case previously identified from newborn urinary screening programs for iminoglycinuria (IG; 242600). IG was reconfirmed in all but 2 of the probands: ... Broer et al. (2008) studied 3 French Canadian and 4 Australian families, each with an index case previously identified from newborn urinary screening programs for iminoglycinuria (IG; 242600). IG was reconfirmed in all but 2 of the probands: in 2 of the Australian families, the probands had only persistent hyperglycinuria (HG). Broer et al. (2008) sequenced 5 known imino acid and glycine transporter candidates and found that the main contribution to IG and HG arose from defects in the gene encoding the proton amino acid transporter SLC36A2 (608331.0001 and 608331.0002), with a classic semidominant inheritance pattern in which 2 nonfunctional alleles conferred the IG phenotype whereas 1 nonfunctional allele was sufficient to confer the HG phenotype. Broer et al. (2008) noted that additional polymorphisms and mutations were identified in the affected individuals in the genes encoding the imino acid transporter SLC6A20 (605616), the putative glycine transporter SLC6A18 (610300), and the neutral amino acid transporter SLC6A19 (608893), and suggested that variation in these genes might also contribute to these phenotypes. Thus, IG and HG exhibit complex molecular explanations depending on a major gene and accompanying modifier genes.