Proximal renal tubular acidosis with ocular abnormalities and mental retardation (Renal tubular acidosis, proximal, with ocular abnormalities and Mental retardation -pRTA-OA-) - Gen SLC4A4.

The proximal renal tubular acidosis with ocular abnormalities and mental retardation (ATRP-OA) is an extremely rare disorder characterized by short stature, intense proximal renal tubular acidosis, mental retardation, bilateral glaucoma, cataracts and band keratopathy. This process is due to failure of proximal tubular cells to reabsorb bicarbonate filtering urine, causing a loss of urinary bicarbonate and subsequent acidemia.

This process is due to mutations in the SLC4A4 gene, located on the long arm of chromosome 4 (4q21). This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of secretion and absorption bicarbonate and intracellular pH. Five variants have been identified transporter NBCe1 (AE). The NBCe1-A transporter is expressed much in the kidney. The NBCe1-A conveyor comprising 14 transmembrane segments. The N-terminal region has 8 segments that are homologous exchanger Cl- / HCO3- (AE1); in contrast, the C-terminal region has 6 transmembrane segments differing exchanger AE1. The conveyor NBCe1-B is distributed in various tissues and is most abundant in pancreas. Both conveyor NBCe1 as AE1 exchanger facilitate transport of bicarbonate into the bloodstream through the basolateral membrane of the renal tubular cell.

They have identified at least 12 mutations in the SLC4A4 gene in people with the disease. Ten missense mutations (NBCe1-A numbering; R298S, S427L, T485S, G486R, R510H, L522P, A799V, R881C, Q29X and W516X); a deletion of the reading frame at nucleotide 2311; the C-terminal 65 bp from exon 23 to intron 23. The pathophysiology of ATRP deletion is explained by the role of the conveyor NBCe1-A in the proximal tubular epithelium. Mutations NBCe1-A causes elimination or decrease its activity. Except for the p.Asn29X mutation, which affects only the NBCe1-A variant, all mutations of ATRP alter the five variants NBCe1 conveyor. Extra renal symptoms are due to defects in the expression of transporters NBCe1-BE or side effects of systemic acidosis as a result of the lack of activity of the transporter NBCe1-A is unknown to what extent.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with proximal renal tubular acidosis with ocular abnormalities and mental retardation, by complete PCR amplification of exons SLC4A4 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).