Renal Tubular Acidosis Sequencing

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. Distal RTA is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while K+ cannot be reabsorbed, leading to acidemia (as H+ builds up in the body) and hypokalemia (as K+ cannot be reabsorbed). This leads to the clinical features of distal RTA. This disorder has been classified by four types: Type 1 Distal, Type 2 Proximal, Type 3 Combined Distal and Proximal, and Type 4.

Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis. While mutations of the SLC4A1 gene have been reported as the sole genetic cause of autosomal dominant distal renal tubular acidosis.

Mutations of the SLC4A4 gene cause the proximal form of RTA. Proximal RTA is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than Distal RTA and the urine can acidify to a pH of less than 5.3.Proximal RTA has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal tubular cells called Fanconi's syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria. The principal feature of Fanconi's syndrome is bone demineralization rickets due to phosphate wasting.

Mutations in the CA2 gene have been found in Type 3 RTA. Patient may present with clinical features associated with distal and proximal RTA. This form of RTA has also been referred to as juvenile RTA. Type 3 RTA is rarely discussed as Types 1,2, and 4 are mainly observed.

Methodology: Sequencing of entire coding region

Purpose: Confirmation of Clinical Diagnosis

ICD-9 code 588.89

Test Requisition: Sequencing Requisition

ATP6V1B1 CPT Code: 81479 Cost: $1193.00

APT6V0A4 CPT Code: 81479 Cost: $1193.00

SLC4A1 CPT Code: 81479 Cost: $1623.00

SLC4A4 CPT Code: 81479 Cost: $1623.00

CA2 CPT Code: 81479 Cost: $763.00

If sequencing all five genes for RTA total cost $6223.00

Turn-around-time: 5-6 weeks for each gene.