DRTA
MCID: RNL045
MIFTS: 45

Renal Tubular Acidosis, Distal (DRTA)

Categories: Bone diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Renal Tubular Acidosis, Distal

MalaCards integrated aliases for Renal Tubular Acidosis, Distal:

Name: Renal Tubular Acidosis, Distal 53
Distal Renal Tubular Acidosis 59 37 29 55 73
Familial Distal Primary Acidosis 59
Renal Tubular Acidosis Type 1 59
Classic Rta 59
Drta 59

Characteristics:

Orphanet epidemiological data:

59
distal renal tubular acidosis
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: All ages; Age of death: normal life expectancy;

Classifications:

Orphanet: 59  
Rare renal diseases


External Ids:

Orphanet 59 ORPHA18
UMLS via Orphanet 74 C1704380 C0259810
ICD10 via Orphanet 34 N25.8
KEGG 37 H00428
UMLS 73 C1704380

Summaries for Renal Tubular Acidosis, Distal

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 18Disease definitionDistal renal tubular acidosis (dRTA) is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis. The classic form is often associated with hypokalemia whereas other forms of acquired dRTA may be associated with hypokalemia, hyperkalemia or normokalemia.EpidemiologyPrevalence of dRTA is unknown but is often underreported. The hereditary forms of dRTA are more prevalent in areas of high consanguinity (Arabic peninsula and North Africa) whereas acquired dRTA has been reported more frequently in Western countries.Clinical descriptionDisease onset can occur at any age, depending on cause. Hereditary dRTA subtypes include autosomal dominant (AD) and autosomal recessive (AR) dRTA (see these terms). A recessive subtype of dRTA associated with anemia has also been described in Southeast Asia. AR forms are frequently diagnosed in infants and young children. AD dRTA is mostly diagnosed in adolescents and young adults. Patients with dRTA can be asymptomatic or can present with polyuria, polydipsia, weakness and fatigue (symptoms associated with hypokalemia). Failure to thrive, rickets, stunting of growth (seen in children) and osteomalacia or osteopenia (seen in adults) are a result of urinary calcium wastage and a loss of calcium salts from the bones. Hypercalciuria, nephrolithiasis and nephrocalcinosis usually occur. Low plasma potassium levels in those with the classic form of dRTA can also cause cardiac arrhythmias, paralysis and even death. In the recessive forms of dRTA, progressive and irreversible deafness often occurs.EtiologydRTA can be acquired or inherited. AD dRTA is usually due to mutations in the SLC4A1 gene (17q21.31). Mutations in the ATP6V1B1 gene (2p13) or ATP6V0A4 gene (7q34) are responsible for AR dRTA with deafness. AR dRTA without deafness or late onset deafness has been mainly described in patients with mutations in the ATP6V0A4 gene but overlap does exist in that some patients with this mutation develop deafness and others do not. Acquired forms of dRTA are thought to be caused by autoimmune diseases such as Sjögren syndrome (see this term) or secondary to other conditions like sickle cell anemia, systemic lupus erythematosus (see these terms), chronic obstructive uropathy, or post-renal transplantation.Diagnostic methodsThe disease is characterized by hyperchloremic metabolic acidosis. The inability to lower urine pH below 5.5 and a positive urine anion gap during spontaneous metabolic acidosis is indicative of dRTA. Provocative tests for further diagnosis include the NH4Cl acidifying test and the furosemide test. Patients with dRTA also show renal potassium wasting except in the hyperkalemic type of dRTA. Molecular genetic testing for one of the causal genetic mutations can also confirm diagnosis.Differential diagnosisThe main differential diagnosis is proximal RTA (see this term) along with other causes of chronic metabolic acidosis (i.e. diarrhea).Antenatal diagnosisAntenatal diagnosis is rarely performed.Genetic counselingThe inherited forms of dRTA are inherited autosomal dominantly or recessively and genetic counseling is possible.Management and treatmentAlkali therapy is the standard treatment (to achieve normal serum bicarbonate levels). Patients are usually given sodium bicarbonate or sodium citrate. Children require very high doses (4-8 meq/kg/day) whereas adults need much lower doses (1-2 meq/kg/day). Potassium replacement is also necessary in hypokalemic patients and potassium citrate is usually recommended. The dose depends on the severity of hypokalemia. Hyperkalemic types require low dietary potassium intake and other therapies.PrognosisAll forms of dRTA are chronic and may have significant effects on growth and development. With treatment there is no decrease in life expectancy and renal failure is uncommon but progressive chronic kidney disease may sometimes occur if there are recurrent kidney stones and when nephrocalcinosis is very severe.Visit the Orphanet disease page for more resources.

MalaCards based summary : Renal Tubular Acidosis, Distal, also known as distal renal tubular acidosis, is related to renal tubular acidosis, distal, autosomal recessive and renal tubular acidosis, distal, autosomal dominant. An important gene associated with Renal Tubular Acidosis, Distal is ATP6V0A4 (ATPase H+ Transporting V0 Subunit A4), and among its related pathways/superpathways are Collecting duct acid secretion and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. The drugs Potassium Citrate and Citric Acid have been mentioned in the context of this disorder. Affiliated tissues include testes, kidney and bone, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

Related Diseases for Renal Tubular Acidosis, Distal

Diseases in the Renal Tubular Acidosis, Distal family:

Renal Tubular Acidosis, Distal, Autosomal Dominant Renal Tubular Acidosis, Distal, Autosomal Recessive
Renal Tubular Acidosis, Distal, Type 3 Renal Tubular Acidosis, Distal, Type 4

Diseases related to Renal Tubular Acidosis, Distal via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 107)
# Related Disease Score Top Affiliating Genes
1 renal tubular acidosis, distal, autosomal recessive 33.7 ATP6V0A4 ATP6V1B1 SLC4A1
2 renal tubular acidosis, distal, autosomal dominant 33.6 ATP6V0A4 ATP6V1B1 SLC4A1
3 nephrocalcinosis 30.5 ATP6V0A4 ATP6V1B1 SLC4A1
4 renal tubular acidosis 30.5 ATP6V0A4 ATP6V1B1 SLC4A1
5 medullary sponge kidney 30.3 ATP6V0A4 ATP6V1B1
6 sensorineural hearing loss 30.2 ATP6V0A4 ATP6V1B1
7 nephrolithiasis 30.1 ATP6V0A4 ATP6V1B1
8 hereditary spherocytosis 30.1 ATP6V0A4 SLC4A1
9 metabolic acidosis 29.7 ATP6V0A4 ATP6V1B1 SLC4A1
10 slc4a1-associated distal renal tubular acidosis 12.9
11 renal tubular acidosis, distal, with hemolytic anemia 12.8
12 renal tubular acidosis, distal, with progressive nerve deafness 12.7
13 renal tubular acidosis, distal, type 3 12.5
14 renal tubular acidosis, distal, with nephrocalcinosis, short stature, mental retardation, and distinctive facies 12.4
15 renal tubular acidosis, distal, type 4 12.4
16 familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis 11.4
17 renal tubular acidosis iii 11.4
18 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.6
19 systemic lupus erythematosus 10.5
20 sjogren syndrome 10.5
21 hypothyroidism 10.5
22 lupus erythematosus 10.5
23 hypokalemia 10.4
24 diabetes insipidus, nephrogenic, autosomal 10.3
25 hypokalemic periodic paralysis, type 1 10.3
26 hyperparathyroidism 10.3
27 diabetes insipidus 10.3
28 autoimmune disease 10.3
29 amelogenesis imperfecta 10.3
30 hemolytic anemia 10.3
31 osteopetrosis 10.3
32 rickets 10.3
33 thyroiditis 10.3
34 biliary cirrhosis, primary, 1 10.2
35 myeloma, multiple 10.2
36 autoimmune hepatitis 10.2
37 diabetes mellitus 10.2
38 hepatitis 10.2
39 primary biliary cirrhosis 10.2
40 thalassemia 10.2
41 bone disease 10.2
42 osteomalacia 10.2
43 interstitial nephritis 10.2
44 respiratory failure 10.2
45 primary hyperparathyroidism 10.2
46 cystic kidney disease 10.2
47 urinary tract obstruction 10.2
48 human immunodeficiency virus infectious disease 10.2
49 hypoaldosteronism 10.2
50 primary biliary cholangitis 10.2

Graphical network of the top 20 diseases related to Renal Tubular Acidosis, Distal:



Diseases related to Renal Tubular Acidosis, Distal

Symptoms & Phenotypes for Renal Tubular Acidosis, Distal

GenomeRNAi Phenotypes related to Renal Tubular Acidosis, Distal according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.32 SLC4A1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.32 ATP6V0A4 SLC4A1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.32 ATP6V0A4
4 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.32 ATP6V0A4
5 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.32 ATP6V0A4
6 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.32 SLC4A1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.32 ATP6V0A4
8 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.32 SLC4A1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.32 SLC4A1

MGI Mouse Phenotypes related to Renal Tubular Acidosis, Distal:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 9.13 ATP6V0A4 ATP6V1B1 SLC4A1
2 taste/olfaction MP:0005394 8.62 ATP6V0A4 ATP6V1B1

Drugs & Therapeutics for Renal Tubular Acidosis, Distal

Drugs for Renal Tubular Acidosis, Distal (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Potassium Citrate Approved, Investigational, Vet_approved Phase 3,Not Applicable
2
Citric Acid Approved, Nutraceutical, Vet_approved Phase 3,Not Applicable 77-92-9 311
3 Citrate Phase 3,Not Applicable
4 Expectorants Phase 3,Not Applicable
5 Natriuretic Agents Phase 3,Not Applicable
6 diuretics Phase 3,Not Applicable
7 Respiratory System Agents Phase 3,Not Applicable
8
Furosemide Approved, Vet_approved 54-31-9 3440
9
Fludrocortisone Approved, Investigational 127-31-1 31378
10
Acetazolamide Approved, Vet_approved Not Applicable 59-66-5 1986
11 Sodium Potassium Chloride Symporter Inhibitors
12 Anti-Inflammatory Agents
13 Calcium, Dietary Not Applicable
14 Anticonvulsants Not Applicable
15 Anticoagulants Not Applicable
16 Carbonic Anhydrase Inhibitors Not Applicable
17 Chelating Agents Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study Evaluating Subjects With Distal Renal Tubular Acidosis Not yet recruiting NCT03644706 Phase 3 ADV7103;Placebos
2 A Study Of Mircera In Patients With Kidney Disease Who Are Not On Dialysis Completed NCT02490514
3 Influence of Polymorphisms in the ATP6V1 Gene of the V-ATPase on the Development of Incomplete Distal Renal Tubular Acidosis Completed NCT01690039 Furosemide-Fludrocortisone-Test (test for urinary acidification)
4 Effects of Potassium Citrate in Urine of Children With Elevated Calcium in Urine and Kidney Stones Completed NCT00120731 Not Applicable Potassium Citrate;Acetazolamide
5 Incidence of Renal Tubular Acidosis in Nephrology Unit in Assiut University Childern Hospital Not yet recruiting NCT03268460

Search NIH Clinical Center for Renal Tubular Acidosis, Distal

Genetic Tests for Renal Tubular Acidosis, Distal

Genetic tests related to Renal Tubular Acidosis, Distal:

# Genetic test Affiliating Genes
1 Distal Renal Tubular Acidosis 29

Anatomical Context for Renal Tubular Acidosis, Distal

MalaCards organs/tissues related to Renal Tubular Acidosis, Distal:

41
Testes, Kidney, Bone, Liver, Thyroid, Colon

Publications for Renal Tubular Acidosis, Distal

Articles related to Renal Tubular Acidosis, Distal:

(show top 50) (show all 414)
# Title Authors Year
1
Distal renal tubular acidosis in two children with acquired hypothyroidism. ( 29716758 )
2018
2
Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families. ( 29573245 )
2018
3
Distal renal tubular acidosis in SjAPgren's syndrome. ( 29657223 )
2018
4
Sjogren's with distal renal tubular acidosis complicating pregnancy. ( 29361865 )
2018
5
Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review. ( 29134448 )
2018
6
Primary distal renal tubular acidosis: novel findings in patients studied by next-generation sequencing. ( 29437164 )
2018
7
Distal renal tubular acidosis. Clinical manifestations in patients with different underlying gene mutations. ( 29725771 )
2018
8
Molecular mechanisms of cutis laxa and distal renal tubular acidosis-causing mutations in V-ATPase<i>a</i>subunits, ATP6V0A2 and ATP6V0A4. ( 29311258 )
2018
9
Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis. ( 29627839 )
2018
10
Distal renal tubular acidosis in a Libyan patient: Evidence for digenic inheritance. ( 29024829 )
2018
11
Targeted Deletion of the Ncoa7 Gene Results in Incomplete Distal Renal Tubular Acidosis in Mice. ( 29384414 )
2018
12
An initial evaluation of hypokalemia turned out distal renal tubular acidosis secondary to parathyroid adenoma. ( 30381523 )
2018
13
Alkaptonuria, a new association of distal renal tubular acidosis. ( 30152443 )
2018
14
Incomplete Distal Renal Tubular Acidosis and Kidney Stones. ( 30139463 )
2018
15
Distal renal tubular acidosis in sickle cell anemia. ( 30152444 )
2018
16
Clinical and genetic analysis of distal renal tubular acidosis in three Chinese children. ( 30230413 )
2018
17
Five Novel Mutations in Chinese Children with Primary Distal Renal Tubular Acidosis. ( 30256676 )
2018
18
Distal renal tubular acidosis secondary to vesico-ureteric reflux: A case report with review of literature. ( 30381529 )
2018
19
A Family with Autosomal Dominant Distal Renal Tubular Acidosis Presents with Atypical Phenotype Caused by a Missence Mutation (R388C) of the Human Kidney Anion Exchanger. ( 30554219 )
2018
20
Distal renal tubular acidosis caused by tryptophan-aspartate repeat domain 72 (WDR72) mutations. ( 30028003 )
2018
21
Low Molecular Weight Proteinuria in Children with Distal Renal Tubular Acidosis. ( 30110261 )
2018
22
Molecular Diagnosis of Solute Carrier Family 4 Member 1 (SLC4A1) Mutation-Related Autosomal Recessive Distal Renal Tubular Acidosis. ( 30124986 )
2018
23
Hypokalemic Distal Renal Tubular Acidosis. ( 30139458 )
2018
24
Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. ( 28994037 )
2017
25
Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome? ( 28553046 )
2017
26
Renal Fanconi syndrome in distal renal tubular acidosis. ( 28293727 )
2017
27
Refining Diagnostic Approaches in Nephrolithiasis: Incomplete Distal Renal Tubular Acidosis. ( 28775128 )
2017
28
The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis. ( 28233610 )
2017
29
I^-COPI mediates the retention of kAE1 G701D protein in Golgi apparatus - a mechanistic explanation of distal renal tubular acidosis associated with the G701D mutation. ( 28646128 )
2017
30
Pathological fracture in SjAPgren's syndrome due to distal renal tubular acidosis. ( 28971585 )
2017
31
An in vitro splicing assay reveals the pathogenicity of a novel intronic variant in ATP6V0A4 for autosomal recessive distal renal tubular acidosis. ( 29202719 )
2017
32
Loss of kAE1 expression in collecting ducts of end-stage kidneys from a family with SLC4A1 G609R-associated distal renal tubular acidosis. ( 28638614 )
2017
33
Clinical and molecular aspects of distal renal tubular acidosis in children. ( 28188436 )
2017
34
Transient Distal Renal Tubular Acidosis in Organophosphate Poisoning. ( 28400690 )
2017
35
New Findings on the Pathogenesis of Distal Renal Tubular Acidosis. ( 29344504 )
2017
36
Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers. ( 28775126 )
2017
37
[Clinical features of hereditary distal renal tubular acidosis and SLC4A1 gene mutation]. ( 28407820 )
2017
38
Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance. ( 28005240 )
2017
39
Erratum to: Clinical and molecular aspects of distal renal tubular acidosis in children. ( 28258487 )
2017
40
Erratum: A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis. ( 27994869 )
2016
41
Failure to thrive and nephrocalcinosis due to distal renal tubular acidosis: A rare presentation of pediatric lupus nephritis. ( 27900972 )
2016
42
Distal renal tubular acidosis without renal impairment after use of tenofovir: a case report. ( 27866471 )
2016
43
Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. ( 27247958 )
2016
44
Clinical and molecular findings in three Moroccan families with distal renal tubular acidosis and deafness: Report of a novel mutation of ATP6V1B1 gene. ( 27140593 )
2016
45
Bilateral Nephrocalcinosis in Primary Distal Renal Tubular Acidosis. ( 27090423 )
2016
46
Distal Renal Tubular Acidosis Associated with Celiac Disease and Thyroiditis. ( 27889732 )
2016
47
Transient distal renal tubular acidosis following hump nosed viper bite: Two cases from Sri Lanka. ( 27752013 )
2016
48
Sjogren's syndrome presenting as Hypokalemic paralysis due to distal renal tubular acidosis. ( 27728182 )
2016
49
The need for genetic study to diagnose some cases of distal renal tubular acidosis. ( 27493007 )
2016
50
A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis. ( 27274828 )
2016

Variations for Renal Tubular Acidosis, Distal

Expression for Renal Tubular Acidosis, Distal

Search GEO for disease gene expression data for Renal Tubular Acidosis, Distal.

Pathways for Renal Tubular Acidosis, Distal

Pathways related to Renal Tubular Acidosis, Distal according to KEGG:

37
# Name Kegg Source Accession
1 Collecting duct acid secretion hsa04966

Pathways related to Renal Tubular Acidosis, Distal according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.63 ATP6V0A4 ATP6V1B1 SLC4A1
2
Show member pathways
11.86 ATP6V0A4 ATP6V1B1
3 11.44 ATP6V0A4 ATP6V1B1
4
Show member pathways
11.24 ATP6V0A4 ATP6V1B1 SLC4A1
5
Show member pathways
11.22 ATP6V0A4 ATP6V1B1
6 10.91 ATP6V0A4 ATP6V1B1

GO Terms for Renal Tubular Acidosis, Distal

Cellular components related to Renal Tubular Acidosis, Distal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.43 ATP6V0A4 ATP6V1B1 SLC4A1
2 apical plasma membrane GO:0016324 9.16 ATP6V0A4 ATP6V1B1
3 basolateral plasma membrane GO:0016323 8.96 ATP6V1B1 SLC4A1
4 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.62 ATP6V0A4 ATP6V1B1

Biological processes related to Renal Tubular Acidosis, Distal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.5 ATP6V0A4 ATP6V1B1 SLC4A1
2 ion transmembrane transport GO:0034220 9.48 ATP6V0A4 ATP6V1B1
3 sensory perception of sound GO:0007605 9.46 ATP6V0A4 ATP6V1B1
4 proton transmembrane transport GO:1902600 9.43 ATP6V0A4 ATP6V1B1
5 ossification GO:0001503 9.4 ATP6V0A4 ATP6V1B1
6 insulin receptor signaling pathway GO:0008286 9.37 ATP6V0A4 ATP6V1B1
7 excretion GO:0007588 9.26 ATP6V0A4 ATP6V1B1
8 transferrin transport GO:0033572 9.16 ATP6V0A4 ATP6V1B1
9 ATP hydrolysis coupled proton transport GO:0015991 8.96 ATP6V0A4 ATP6V1B1
10 regulation of pH GO:0006885 8.62 ATP6V0A4 ATP6V1B1

Molecular functions related to Renal Tubular Acidosis, Distal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proton transmembrane transporter activity GO:0015078 8.62 ATP6V0A4 ATP6V1B1

Sources for Renal Tubular Acidosis, Distal

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36 IUPHAR
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45 MESH via Orphanet
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74 UMLS via Orphanet
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