Distal renal tubular acidosis associated with SLC4A1 syndrome ..., (SLC4A1 -Associated distal renal tubular acidosis Syndrome) - Gen SLC4A1
The distal renal tubular acidosis associated with SLC4A1, renal impairment is sometimes including abnormalities of blood cells. In people with distal renal tubular acidosis associated with SLC4A1, kidneys can not adequately remove acidic metabolites body and acidified blood pH, causing a chemical imbalance called metabolic acidosis. The inability to remove acid metabolites of the body often causes slow growth and rickets in children and osteomalacia in adults. This bone disorder characterized by bone pain, bowlegged and difficulty walking. In addition, most children and adults with distal renal tubular acidosis associated with SLC4A1 have hypercalciuria, nephrolithiasis and nephrocalcinosis. In some cases, these renal anomalies result in hypokalemia. In rare cases, these renal abnormalities can lead to renal failure, life - threatening.
The clinico-pathogenetic picture described, corresponds to the distal renal tubular acidosis complete, which usually occurs in childhood. Some people do not develop metabolic acidosis despite their kidneys have difficulty clearing the acid metabolites, which corresponds to a renal distal incomplete tubular acidosis, which may also have some of the characteristics of the entire shape such as bone problems and nephrolithiasis. Often people who initially are incompletely developed later in life, completely. Some people with distal renal tubular acidosis associated with SLC4A1, also have abnormal blood cells that may vary in severity of symptoms, and sometimes suffer from hemolytic anemia, with proper signs it: pale skin, fatigue, dyspnea and splenomegaly.
They described two forms of distal renal tubular acidosis associated with SLC4A1 distinguished by their pattern of inheritance. Autosomal dominant form is more common and usually less severe than autosomal recessive form. The autosomal dominant form may be associated with complete or incomplete distal renal tubular acidosis, and is rarely associated with abnormalities of blood cells. Autosomal recessive is always associated with complete distal renal tubular acidosis and most often associated with abnormalities of blood cells, but not all people with this form have abnormal blood cells.
This process has been linked to mutations in the SLC4A1 gene located on the short arm of chromosome 17 (17q21.31). This gene encodes AE1 (anion exchanger 1) protein, which carries anions through cell membranes in order to maintain the correct pH in the body. Two versions of the AE1 protein that differ in size. The shorter version is in the specialized kidney cells called alpha cells, which are found in the renal tubules. Renal tubules reabsorb substances that are necessary, and eliminated in urine metabolites that are not necessary. Specifically, alpha cells, through this exchanger system, eliminate acidic products in the urine to be eliminated from the body. The longer version of the AE1 protein is found in the blood erythrocytes, where it binds to other proteins that comprise the cytoskeleton of the blood erythrocytes, helping maintain its structure, by interacting with another protein called glycophorin A, which collaborates the AE1 protein reaches its correct location.
They have identified at least 18 SLC4A1 gene mutations in people with distal renal tubular acidosis. These genetic changes lead to encoding altered AE1 proteins that can not be placed correctly on the cell membrane, where it should perform the exchange of chloride ions, negatively charged by bicarbonate ions, also negatively charged, acting as a heat exchanger a chloride bicarbonate exchanger (Cl - / HCO 3 -). Through this exchange, the correct levels of organic acidity (pH) are maintained. Therefore, mutations in the SLC4A1 gene interrupts the exchange bicarbonate, and as a result, the acid can not be released into the urine and accumulates in the blood, leading to metabolic acidosis. The inability to remove the acid from the body also causes the other features of the distal renal tubular acidosis, including nephrocalcinosis and nephrolithiasis. It is believed that with the help of glycophorin A, altered AE1 protein can frequently reach the membrane of the blood erythrocytes, which explains why most people with distal renal tubular acidosis associated with SLC4A1 no abnormalities in cells blood.
The distal renal tubular acidosis associated with SLC4A1 can have different patterns of inheritance. Usually it is inherited in an autosomal dominant pattern, which means that a copy of the altered SLC4A1 gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. Less commonly, the distal renal tubular acidosis associated with SLC4A1 has an autosomal recessive inheritance pattern, which means that 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 performed in IVAMI: in IVAMI perform detection of mutations associated with syndrome distal renal tubular acidosis associated with SLC4A1, by complete PCR amplification of exons SLC4A1 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).