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Bartter disease type 2(BARTS2)

MedGen UID:
343428
Concept ID:
C1855849
Disease or Syndrome
Synonyms: Bartter syndrome, type 2, antenatal; Hyperprostaglandin E syndrome 2; HYPOKALEMIC ALKALOSIS WITH HYPERCALCIURIA 2, ANTENATAL
SNOMED CT: Bartter syndrome antenatal type 2 (700109009); Bartter's syndrome type 2 (700109009); Hyperprostaglandin E syndrome type 2 (700109009); Hypokalemic alkalosis with hypercalciuria antenatal type 2 (700109009)
 
Gene (location): KCNJ1 (11q24.3)
 
Monarch Initiative: MONDO:0009424
OMIM®: 241200
Orphanet: ORPHA620220

Definition

Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364. [from OMIM]

Clinical features

From HPO
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Hyposthenuria
MedGen UID:
68565
Concept ID:
C0232831
Finding
An abnormally low urinary specific gravity, i.e., reduced concentration of solutes in the urine.
Renal salt wasting
MedGen UID:
375868
Concept ID:
C1846347
Finding
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
Renal potassium wasting
MedGen UID:
339499
Concept ID:
C1846348
Finding
High urine potassium in the presence of hypokalemia.
Increased urinary potassium
MedGen UID:
337562
Concept ID:
C1846351
Finding
An increased concentration of potassium(1+) in the urine.
Hyperchloriduria
MedGen UID:
337563
Concept ID:
C1846352
Finding
An increased concentration of chloride in the urine.
Renal juxtaglomerular cell hypertrophy/hyperplasia
MedGen UID:
356547
Concept ID:
C1866496
Finding
Increased number and size of the juxtaglomerular cells.
Hyperprostaglandinuria
MedGen UID:
401015
Concept ID:
C1866498
Finding
An increased concentration of prostaglandin in the urine.
Low-to-normal blood pressure
MedGen UID:
356549
Concept ID:
C1866500
Finding
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
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.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Impaired platelet aggregation
MedGen UID:
383786
Concept ID:
C1855853
Finding
An impairment in the rate and degree to which platelets aggregate after the addition of an agonist that stimulates platelet clumping. Platelet aggregation is measured using aggregometer to measure the optical density of platelet-rich plasma, whereby platelet aggregation causes the plasma to become more transparent.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Tetany
MedGen UID:
11748
Concept ID:
C0039621
Finding
A condition characterized by intermittent involuntary contraction of muscles (spasms) related to hypocalcemia or occasionally magnesium deficiency.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Chondrocalcinosis
MedGen UID:
154303
Concept ID:
C0553730
Disease or Syndrome
Radiographic evidence of articular calcification that represent calcium pyrophosphate depositions in soft tissue surrounding joints and at the insertions of tendons near joints (Entheses/Sharpey fibers) .
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Hypochloremia
MedGen UID:
39088
Concept ID:
C0085680
Disease or Syndrome
An abnormally decreased chloride concentration in the blood.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.
Hypokalemic metabolic alkalosis
MedGen UID:
152852
Concept ID:
C0740898
Disease or Syndrome
Increased serum prostaglandin E2
MedGen UID:
461708
Concept ID:
C3150358
Finding
An increased concentration of prostaglandin E2 in the blood.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Fetal polyuria
MedGen UID:
355948
Concept ID:
C1865279
Finding
Abnormally increased production of urine by the fetus resulting in polyhydramnios.
Increased circulating aldosterone concentration
MedGen UID:
6960
Concept ID:
C0020428
Disease or Syndrome
Overproduction of the mineralocorticoid aldosterone by the adrenal cortex.
Increased circulating renin concentration
MedGen UID:
66818
Concept ID:
C0240783
Finding
An increased level of renin in the blood.
Hyperactive renin-angiotensin system
MedGen UID:
335401
Concept ID:
C1846345
Finding
An abnormally increased activity of the renin-angiotensin system, causing hypertension by a combination of volume excess and vasoconstrictor mechanisms.
Abnormally large globe
MedGen UID:
344595
Concept ID:
C1855852
Finding
Diffusely large eye (with megalocornea) without glaucoma.

Professional guidelines

PubMed

Honka H, Salehi M
Curr Opin Clin Nutr Metab Care 2019 Jul;22(4):295-302. doi: 10.1097/MCO.0000000000000574. PMID: 31082828Free PMC Article
Matsunoshita N, Nozu K, Shono A, Nozu Y, Fu XJ, Morisada N, Kamiyoshi N, Ohtsubo H, Ninchoji T, Minamikawa S, Yamamura T, Nakanishi K, Yoshikawa N, Shima Y, Kaito H, Iijima K
Genet Med 2016 Feb;18(2):180-8. Epub 2015 Apr 16 doi: 10.1038/gim.2015.56. PMID: 25880437
Assadi F
Iran J Kidney Dis 2008 Jul;2(3):115-22. PMID: 19377223

Recent clinical studies

Diagnosis

Zieg J, Doležel Z
Cas Lek Cesk 2022 Summer;161(3-4):131-134. PMID: 36100451
Huang L, Luiken GP, van Riemsdijk IC, Petrij F, Zandbergen AA, Dees A
Neth J Med 2014 Feb;72(2):91-3. PMID: 24659592
Gonzales PA, Pisitkun T, Hoffert JD, Tchapyjnikov D, Star RA, Kleta R, Wang NS, Knepper MA
J Am Soc Nephrol 2009 Feb;20(2):363-79. Epub 2008 Dec 3 doi: 10.1681/ASN.2008040406. PMID: 19056867Free PMC Article
Assadi F
Iran J Kidney Dis 2008 Jul;2(3):115-22. PMID: 19377223
Toyoda K, Miyamoto Y, Ida M, Tada S, Utsunomiya M
Radiology 1989 Nov;173(2):431-4. doi: 10.1148/radiology.173.2.2678257. PMID: 2678257

Therapy

de Lavillandre JLB, Buron F, Ducroux E, Kanitakis J
Skinmed 2022;20(2):145-148. Epub 2022 Apr 30 PMID: 35532771
Honka H, Salehi M
Curr Opin Clin Nutr Metab Care 2019 Jul;22(4):295-302. doi: 10.1097/MCO.0000000000000574. PMID: 31082828Free PMC Article
Matsunoshita N, Nozu K, Shono A, Nozu Y, Fu XJ, Morisada N, Kamiyoshi N, Ohtsubo H, Ninchoji T, Minamikawa S, Yamamura T, Nakanishi K, Yoshikawa N, Shima Y, Kaito H, Iijima K
Genet Med 2016 Feb;18(2):180-8. Epub 2015 Apr 16 doi: 10.1038/gim.2015.56. PMID: 25880437
Carmosino M, Procino G, Svelto M
Biol Cell 2012 Apr;104(4):201-12. Epub 2012 Jan 26 doi: 10.1111/boc.201100049. PMID: 22211456
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Iran J Kidney Dis 2008 Jul;2(3):115-22. PMID: 19377223

Prognosis

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Tschernoster N, Erger F, Kohl S, Reusch B, Wenzel A, Walsh S, Thiele H, Becker C, Franitza M, Bartram MP, Kömhoff M, Schumacher L, Kukat C, Borodina T, Quedenau C, Nürnberg P, Rinschen MM, Driller JH, Pedersen BP, Schlingmann KP, Hüttel B, Bockenhauer D, Beck B, Altmüller J
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Pediatr Dev Pathol 2015 Jul-Aug;18(4):324-6. Epub 2015 Apr 29 doi: 10.2350/14-08-1543-CR.1. PMID: 25923035

Clinical prediction guides

Tschernoster N, Erger F, Kohl S, Reusch B, Wenzel A, Walsh S, Thiele H, Becker C, Franitza M, Bartram MP, Kömhoff M, Schumacher L, Kukat C, Borodina T, Quedenau C, Nürnberg P, Rinschen MM, Driller JH, Pedersen BP, Schlingmann KP, Hüttel B, Bockenhauer D, Beck B, Altmüller J
Genome Med 2023 Aug 23;15(1):62. doi: 10.1186/s13073-023-01215-1. PMID: 37612755Free PMC Article
Verploegen MFA, Vargas-Poussou R, Walsh SB, Alpay H, Amouzegar A, Ariceta G, Atmis B, Bacchetta J, Bárány P, Baron S, Bayrakci US, Belge H, Besouw M, Blanchard A, Bökenkamp A, Boyer O, Burgmaier K, Calò LA, Decramer S, Devuyst O, van Dyck M, Ferraro PM, Fila M, Francisco T, Ghiggeri GM, Gondra L, Guarino S, Hooman N, Hoorn EJ, Houillier P, Kamperis K, Kari JA, Konrad M, Levtchenko E, Lucchetti L, Lugani F, Marzuillo P, Mohidin B, Neuhaus TJ, Osman A, Papizh S, Perelló M, Rookmaaker MB, Conti VS, Santos F, Sawaf G, Serdaroglu E, Szczepanska M, Taroni F, Topaloglu R, Trepiccione F, Vidal E, Wan ER, Weber L, Yildirim ZY, Yüksel S, Zlatanova G, Bockenhauer D, Emma F, Nijenhuis T
Nephrol Dial Transplant 2022 Nov 23;37(12):2474-2486. doi: 10.1093/ndt/gfac029. PMID: 35137195Free PMC Article
Koumangoye R, Bastarache L, Delpire E
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Lopez HU, Haverfield E, Chung WK
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Andrini O, Keck M, Briones R, Lourdel S, Vargas-Poussou R, Teulon J
Am J Physiol Renal Physiol 2015 Jun 15;308(12):F1324-34. Epub 2015 Mar 25 doi: 10.1152/ajprenal.00004.2015. PMID: 25810436

Recent systematic reviews

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