Thus, gyrate atrophy can be found with either disorder, with proline deficiency as an underlying feature.Hyperglycinuria is another disorder affecting reabsorption of glycine and imino acids, similar to iminoglycinuria and considered to be a heterozygous form. When accompanied by a specific type of kidney stone (nephrolithiasis), it is sometimes referred to as "iminoglycinuria, type II". Genetics
Iminoglycinuria is believed to be inherited in an autosomal recessive manner. This means a defective gene responsible for the disorder is located on an autosome, and inheritance requires two copies of the defective gene—one from each parent. Parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.A non-inherited cause of excess urinary excretion of proline and glycine, similar to that found in iminoglycinuria, is quite common to newborn infants younger than six months. Sometimes referred to as neonatal iminoglycinuria, it is due to underdevelopment of high-affinity transport mechanisms within the renal circuit, specifically PAT2, SIT1 and SLC6A18. The condition corrects itself with age. In cases where this persists beyond childhood, however, inherited hyperglycinuria or iminoglycinuria may be suspected. Pathophysiology
Glycine, proline and hydroxyproline share common renal tubular mechanisms of reabsorption, a function specific to the proximal tubule. Both reabsorption or absorption of glycine and imino acids takes place respectively at the proximal tubule or intestinal brush border epithelium.
Absorption refers to the overall process happening in the intestine in lieu of normal digestive breakdown of proteins, while reabsorption refers to the process occurring in the renal proximal tubule to reclaim amino and imino acids that have been filtered out of the blood via the glomerulus.These forms of transport require energy, as the products being transported are usually moving against a higher concentration gradient. This process, called active transport, get its energy from ATP and other ATP-related cotransport systems that produce energy, like the sodium-potassium pump. Mechanism
The primary defect associated with iminoglycinuria is a homozygous (recessive) mutation of the SLC36A2 (PAT2) gene. One of several membrane transport proteins in the solute carrier family of amino acid transporters, PAT2 is the high-affinity renal transporter of glycine, proline and hydroxyproline found to be defective in both alleles when iminoglycinuria is present in an individual. This is in contrast to the fact that when only one PAT2 allele is defective, hyperglycinuria will be present instead of iminoglycinuria. These findings delineate iminoglycinuria as the homozygous form of hyperglycinuria, with the former having a higher degree of urinary excretion of glycine and imino acids correlating to mutations in both alleles.Another mutation suspected to convey the iminoglycinuria phenotype may be found in the SLC36A1 (PAT1) gene. Identified as the low-affinity intestinal transporter of glycine and imino acids, PAT1 works in cooperation with the renal sodium-hydrogen exchanger NHE3 (SLC9A3).