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Diabetes insipidus, nephrogenic, X-linked(NDI1)

MedGen UID:
288785
Concept ID:
C1563705
Disease or Syndrome
Synonyms: Diabetes insipidus nephrogenic type 1; Nephrogenic Diabetes Insipidus, Type I
 
Gene (location): AVPR2 (Xq28)
 
Monarch Initiative: MONDO:0010581
OMIM®: 304800

Disease characteristics

Excerpted from the GeneReview: Hereditary Nephrogenic Diabetes Insipidus
Hereditary nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals. [from GeneReviews]
Authors:
Nine Knoers  |  Henny Lemmink   view full author information

Additional descriptions

From OMIM
Nephrogenic diabetes insipidus (NDI) is caused by the inability of the renal collecting ducts to absorb water in response to antidiuretic hormone (ADH), also known as arginine vasopressin (AVP; 192340). Approximately 90% of patients are males with the X-linked recessive form (type I; NDI1), which is caused by a defect in the vasopressin V2 receptor in renal collecting duct cells. The remaining 10% of patients have autosomal NDI (type II; NDI2, 125800), which is caused by mutations in the gene encoding the aquaporin-2 water channel (AQP2; 107777) on chromosome 12q13 (Morello and Bichet, 2001). Neurogenic, or central, diabetes insipidus (125700) is caused by mutation in the gene encoding arginine vasopressin, located on 20p13.  http://www.omim.org/entry/304800
From MedlinePlus Genetics
Infants with familial arginine vasopressin resistance tend to have problems feeding and gaining weight (failure to thrive). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan.

Arginine vasopressin resistance can be either acquired or familial. The acquired form can occur at any time during life. The familial form usually become apparent within the first year of life, though in some cases they develop in adolescence or early adulthood.

Affected individuals can quickly become dehydrated if they do not drink enough water. Dehydration can cause dizziness and fatigue. Prolonged dehydration can lead to confusion, low blood pressure, seizures, and coma. People with arginine vasopressin resistance often develop high levels of sodium in the blood (hypernatremia) due to dehydration. Repeated cycles of dehydration can cause long-term health problems, particularly in children. 

Researchers have recommended using the condition name arginine vasopressin resistance because the previous name, nephrogenic diabetes insipidus, was often confused with a much more common disorder called diabetes mellitus. Arginine vasopressin resistance and diabetes mellitus are separate disorders with different features, causes, and treatment.

Arginine vasopressin resistance (previously called nephrogenic diabetes insipidus) is a disorder of water balance. The body normally balances fluid intake by releasing excess fluid in urine. However, people with arginine vasopressin resistance produce an excessive amount of urine (polyuria), which depletes the amount of water in the body. This water loss also leads to excessive thirst (polydipsia).   https://medlineplus.gov/genetics/condition/arginine-vasopressin-resistance

Clinical features

From HPO
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Megacystis
MedGen UID:
343318
Concept ID:
C1855311
Finding
Dilatation of the bladder postnatally.
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.
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.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
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.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
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.
Hypernatremia
MedGen UID:
6966
Concept ID:
C0020488
Disease or Syndrome
An abnormally increased sodium concentration in the blood.
Hypertonic dehydration
MedGen UID:
205119
Concept ID:
C1112601
Disease or Syndrome
Unexplained fevers
MedGen UID:
337055
Concept ID:
C1844662
Finding
Episodes of fever for which no infectious cause can be identified.
Diabetes insipidus
MedGen UID:
8349
Concept ID:
C0011848
Disease or Syndrome
A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Los EL, Deen PM, Robben JH
J Neuroendocrinol 2010 May;22(5):393-9. Epub 2010 Feb 12 doi: 10.1111/j.1365-2826.2010.01983.x. PMID: 20163515
Bernier V, Morello JP, Zarruk A, Debrand N, Salahpour A, Lonergan M, Arthus MF, Laperrière A, Brouard R, Bouvier M, Bichet DG
J Am Soc Nephrol 2006 Jan;17(1):232-43. Epub 2005 Nov 30 doi: 10.1681/ASN.2005080854. PMID: 16319185

Recent clinical studies

Therapy

Habiby R, Bichet DG, Arthus MF, Connaughton D, Shril S, Mane S, Majmundar AJ, Hildebrandt F, Robertson GL
J Clin Endocrinol Metab 2022 May 17;107(6):e2513-e2522. doi: 10.1210/clinem/dgac076. PMID: 35137152Free PMC Article
Mouillac B, Mendre C
Handb Exp Pharmacol 2018;245:63-83. doi: 10.1007/164_2017_50. PMID: 28939971
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947
Faerch M, Christensen JH, Corydon TJ, Kamperis K, de Zegher F, Gregersen N, Robertson GL, Rittig S
Clin Endocrinol (Oxf) 2008 Mar;68(3):395-403. Epub 2007 Oct 17 doi: 10.1111/j.1365-2265.2007.03054.x. PMID: 17941907
Robben JH, Deen PM
BioDrugs 2007;21(3):157-66. doi: 10.2165/00063030-200721030-00003. PMID: 17516711

Prognosis

Kobayashi S, Mizuno N, Yokoi K, Mori T, Sohara E, Uchida S
Medicine (Baltimore) 2022 Jan 21;101(3):e28552. doi: 10.1097/MD.0000000000028552. PMID: 35060513Free PMC Article
Bockenhauer D, Bichet DG
Curr Opin Pediatr 2017 Apr;29(2):199-205. doi: 10.1097/MOP.0000000000000473. PMID: 28134709
Faerch M, Christensen JH, Corydon TJ, Kamperis K, de Zegher F, Gregersen N, Robertson GL, Rittig S
Clin Endocrinol (Oxf) 2008 Mar;68(3):395-403. Epub 2007 Oct 17 doi: 10.1111/j.1365-2265.2007.03054.x. PMID: 17941907
Birnbaumer M
Arch Med Res 1999 Nov-Dec;30(6):465-74. doi: 10.1016/s0188-4409(99)00063-6. PMID: 10714359
Bichet DG, Hendy GN, Lonergan M, Arthus MF, Ligier S, Pausova Z, Kluge R, Zingg H, Saenger P, Oppenheimer E
Am J Hum Genet 1992 Nov;51(5):1089-1102. PMID: 1357965Free PMC Article

Clinical prediction guides

Ghasemi S, Mojbafan M, Talebi S, Hooman N, Hoseini R
Mol Genet Genomic Med 2024 Apr;12(4):e2421. doi: 10.1002/mgg3.2421. PMID: 38622833Free PMC Article
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947
Bockenhauer D, Carpentier E, Rochdi D, van't Hoff W, Breton B, Bernier V, Bouvier M, Bichet DG
Nephron Physiol 2010;114(1):p1-10. Epub 2009 Oct 8 doi: 10.1159/000245059. PMID: 19816050
Faerch M, Christensen JH, Corydon TJ, Kamperis K, de Zegher F, Gregersen N, Robertson GL, Rittig S
Clin Endocrinol (Oxf) 2008 Mar;68(3):395-403. Epub 2007 Oct 17 doi: 10.1111/j.1365-2265.2007.03054.x. PMID: 17941907
Bichet DG, Hendy GN, Lonergan M, Arthus MF, Ligier S, Pausova Z, Kluge R, Zingg H, Saenger P, Oppenheimer E
Am J Hum Genet 1992 Nov;51(5):1089-1102. PMID: 1357965Free PMC Article

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