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Renal tubular acidosis, distal, 4, with hemolytic anemia(DRTA4)

MedGen UID:
1771439
Concept ID:
C5436235
Disease or Syndrome
Synonym: Renal tubular acidosis, distal, with hemolytic anemia
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): SLC4A1 (17q21.31)
 
Monarch Initiative: MONDO:0012700
OMIM®: 611590
Orphanet: ORPHA93610

Disease characteristics

Excerpted from the GeneReview: Hereditary Distal Renal Tubular Acidosis
Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA). [from GeneReviews]
Authors:
R Todd Alexander  |  Linda Law  |  Helena Gil-Peña, et. al.   view full author information

Clinical features

From HPO
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Isothenuria
MedGen UID:
868273
Concept ID:
C4022665
Disease or Syndrome
Inability of the kidneys to produce either concentrated or dilute urine.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Anorexia
MedGen UID:
315
Concept ID:
C0003123
Disease or Syndrome
Anorexia, or the loss of appetite for food, is a medical condition.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Reticulocytosis
MedGen UID:
60089
Concept ID:
C0206160
Finding
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
Decreased mean corpuscular volume
MedGen UID:
1375398
Concept ID:
C0855790
Finding
A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters).
Rickets
MedGen UID:
48470
Concept ID:
C0035579
Disease or Syndrome
Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Distal renal tubular acidosis
MedGen UID:
853429
Concept ID:
C1704380
Disease or Syndrome
A type of renal tubular acidosis characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. The urine cannot be acidified below a pH of 5.3, associated with acidemia and hypokalemia.
Hyperchloremic metabolic acidosis
MedGen UID:
369924
Concept ID:
C1969073
Disease or Syndrome
A form of metabolic acidosis with increased serum chloride levels.
Pallor
MedGen UID:
10547
Concept ID:
C0030232
Finding
Abnormally pale skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRenal tubular acidosis, distal, 4, with hemolytic anemia

Recent clinical studies

Etiology

Sinha R, Pradhan S, Banerjee S, Jahan A, Akhtar S, Pahari A, Raut S, Parakh P, Basu S, Srivastava P, Nayak S, Thenral SG, Ramprasad V, Ashton E, Bockenhauer D, Mandal K
Pediatr Nephrol 2022 Aug;37(8):1811-1836. Epub 2022 Jan 10 doi: 10.1007/s00467-021-05388-y. PMID: 35006361
Cazenave M, Audard V, Bertocchio JP, Habibi A, Baron S, Prot-Bertoye C, Berkenou J, Maruani G, Stehlé T, Cornière N, Ayari H, Friedlander G, Galacteros F, Houillier P, Bartolucci P, Courbebaisse M
Clin J Am Soc Nephrol 2020 Jan 7;15(1):16-24. Epub 2019 Dec 10 doi: 10.2215/CJN.07830719. PMID: 31822527Free PMC Article
Reithmeier RA, Casey JR, Kalli AC, Sansom MS, Alguel Y, Iwata S
Biochim Biophys Acta 2016 Jul;1858(7 Pt A):1507-32. Epub 2016 Apr 6 doi: 10.1016/j.bbamem.2016.03.030. PMID: 27058983
Bruce LJ, Tanner MJ
Baillieres Best Pract Res Clin Haematol 1999 Dec;12(4):637-54. doi: 10.1053/beha.1999.0046. PMID: 10895257
Oster JR, Lee SM, Lespier LE, Pellegrini EL, Vaamonde CA
Arch Intern Med 1976 Jan;136(1):30-5. PMID: 2128

Diagnosis

Sinha R, Pradhan S, Banerjee S, Jahan A, Akhtar S, Pahari A, Raut S, Parakh P, Basu S, Srivastava P, Nayak S, Thenral SG, Ramprasad V, Ashton E, Bockenhauer D, Mandal K
Pediatr Nephrol 2022 Aug;37(8):1811-1836. Epub 2022 Jan 10 doi: 10.1007/s00467-021-05388-y. PMID: 35006361
Cazenave M, Audard V, Bertocchio JP, Habibi A, Baron S, Prot-Bertoye C, Berkenou J, Maruani G, Stehlé T, Cornière N, Ayari H, Friedlander G, Galacteros F, Houillier P, Bartolucci P, Courbebaisse M
Clin J Am Soc Nephrol 2020 Jan 7;15(1):16-24. Epub 2019 Dec 10 doi: 10.2215/CJN.07830719. PMID: 31822527Free PMC Article
Agrwal S, Mantan M, Dabas A
Iran J Kidney Dis 2019 Sep;13(5):337-339. PMID: 31705751
Bharani A, Manchanda R, Singh RK, Prashant S
Saudi J Kidney Dis Transpl 2018 Jul-Aug;29(4):1000-1004. doi: 10.4103/1319-2442.239637. PMID: 30152444
Vasuvattakul S, Yenchitsomanus PT, Vachuanichsanong P, Thuwajit P, Kaitwatcharachai C, Laosombat V, Malasit P, Wilairat P, Nimmannit S
Kidney Int 1999 Nov;56(5):1674-82. doi: 10.1046/j.1523-1755.1999.00756.x. PMID: 10571775

Therapy

Barathidasan GS, Krishnamurthy S, Karunakar P, Rajendran R, Ramya K, Dhandapany G, Ramamoorthy JG, Ganesh RN
CEN Case Rep 2020 May;9(2):129-132. Epub 2019 Dec 18 doi: 10.1007/s13730-019-00440-1. PMID: 31853802Free PMC Article
Cazenave M, Audard V, Bertocchio JP, Habibi A, Baron S, Prot-Bertoye C, Berkenou J, Maruani G, Stehlé T, Cornière N, Ayari H, Friedlander G, Galacteros F, Houillier P, Bartolucci P, Courbebaisse M
Clin J Am Soc Nephrol 2020 Jan 7;15(1):16-24. Epub 2019 Dec 10 doi: 10.2215/CJN.07830719. PMID: 31822527Free PMC Article
Papadopoulos N, Vasiliki A, Aloizos G, Tapinis P, Kikilas A
Ann Pharmacother 2010 Jan;44(1):219-21. Epub 2009 Nov 24 doi: 10.1345/aph.1M440. PMID: 19934389
Ballaban-Gil K, Callahan C, O'Dell C, Pappo M, Moshé S, Shinnar S
Epilepsia 1998 Jul;39(7):744-8. doi: 10.1111/j.1528-1157.1998.tb01160.x. PMID: 9670903

Prognosis

Hsiao PJ, Wang SC, Wen MC, Diang LK, Lin SH
Am J Kidney Dis 2010 Jan;55(1):e1-5. Epub 2009 Oct 14 doi: 10.1053/j.ajkd.2009.07.022. PMID: 19833423
Khositseth S, Sirikanerat A, Wongbenjarat K, Opastirakul S, Khoprasert S, Peuksungnern R, Wattanasirichaigoon D, Thongnoppakhun W, Viprakasit V, Yenchitsomanus PT
Am J Kidney Dis 2007 Jun;49(6):841-850.e1. doi: 10.1053/j.ajkd.2007.03.002. PMID: 17533027
Ribeiro ML, Alloisio N, Almeida H, Gomes C, Texier P, Lemos C, Mimoso G, Morlé L, Bey-Cabet F, Rudigoz RC, Delaunay J, Tamagnini G
Blood 2000 Aug 15;96(4):1602-4. PMID: 10942416
Ballaban-Gil K, Callahan C, O'Dell C, Pappo M, Moshé S, Shinnar S
Epilepsia 1998 Jul;39(7):744-8. doi: 10.1111/j.1528-1157.1998.tb01160.x. PMID: 9670903
Bakir AA, Hathiwala SC, Ainis H, Hryhorczuk DO, Rhee HL, Levy PS, Dunea G
Am J Nephrol 1987;7(2):110-5. doi: 10.1159/000167444. PMID: 3605231

Clinical prediction guides

Kaewboonlert N, Wattanapanitch M, Praditsap O, Deejai N, Chanprasert C, Sawasdee N, Nettuwakul C, Wanachiwanawin W, Sritippayawan S, Thamtarana PJ, Yenchitsomanus PT, Rungroj N
Stem Cell Res 2023 Mar;67:103043. Epub 2023 Feb 10 doi: 10.1016/j.scr.2023.103043. PMID: 36791635
Khositseth S, Sirikanaerat A, Khoprasert S, Opastirakul S, Kingwatanakul P, Thongnoppakhun W, Yenchitsomanus PT
Am J Hematol 2008 Jun;83(6):465-71. doi: 10.1002/ajh.21151. PMID: 18266205
Khositseth S, Sirikanerat A, Wongbenjarat K, Opastirakul S, Khoprasert S, Peuksungnern R, Wattanasirichaigoon D, Thongnoppakhun W, Viprakasit V, Yenchitsomanus PT
Am J Kidney Dis 2007 Jun;49(6):841-850.e1. doi: 10.1053/j.ajkd.2007.03.002. PMID: 17533027
de Santis Feltran L, de Abreu Carvalhaes JT, Sesso R
Paediatr Drugs 2002;4(1):29-36. doi: 10.2165/00128072-200204010-00004. PMID: 11817984
Vasuvattakul S, Yenchitsomanus PT, Vachuanichsanong P, Thuwajit P, Kaitwatcharachai C, Laosombat V, Malasit P, Wilairat P, Nimmannit S
Kidney Int 1999 Nov;56(5):1674-82. doi: 10.1046/j.1523-1755.1999.00756.x. PMID: 10571775

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