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Alport syndrome

MedGen UID:
339209
Concept ID:
C1567741
Disease or Syndrome
Synonyms: Congenital hereditary hematuria; Hemorrhagic familial nephritis; Hemorrhagic hereditary nephritis
SNOMED CT: Alport syndrome (770414008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
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.
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Source: Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
 
Genes (locations): COL4A3 (2q36.3); COL4A4 (2q36.3); COL4A5 (Xq22.3)
 
Monarch Initiative: MONDO:0018965
OMIM® Phenotypic series: PS301050
Orphanet: ORPHA63

Definition

Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.

People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys gradually lose their ability to efficiently remove waste products from the body, resulting in end-stage kidney disease (ESKD).

In late childhood or early adolescence, many people with Alport syndrome develop sensorineural hearing loss, which is caused by abnormalities of the inner ear. Affected individuals may also have misshapen lenses in their eyes (anterior lenticonus) and abnormal coloration of the retina, which is the light-sensitive tissue at the back of the eye. These eye abnormalities seldom lead to vision loss.

 [from MedlinePlus Genetics]

Professional guidelines

PubMed

Savige J, Lipska-Zietkiewicz BS, Watson E, Hertz JM, Deltas C, Mari F, Hilbert P, Plevova P, Byers P, Cerkauskaite A, Gregory M, Cerkauskiene R, Ljubanovic DG, Becherucci F, Errichiello C, Massella L, Aiello V, Lennon R, Hopkinson L, Koziell A, Lungu A, Rothe HM, Hoefele J, Zacchia M, Martic TN, Gupta A, van Eerde A, Gear S, Landini S, Palazzo V, Al-Rabadi L, Claes K, Corveleyn A, Van Hoof E, van Geel M, Williams M, Ashton E, Belge H, Ars E, Bierzynska A, Gangemi C, Renieri A, Storey H, Flinter F
Clin J Am Soc Nephrol 2022 Jan;17(1):143-154. Epub 2021 Dec 20 doi: 10.2215/CJN.04230321. PMID: 34930753Free PMC Article
Kashtan CE, Gross O
Pediatr Nephrol 2021 Mar;36(3):711-719. Epub 2020 Nov 6 doi: 10.1007/s00467-020-04819-6. PMID: 33159213
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016

Recent clinical studies

Etiology

Puapatanakul P, Miner JH
Curr Opin Nephrol Hypertens 2024 May 1;33(3):283-290. Epub 2024 Mar 13 doi: 10.1097/MNH.0000000000000983. PMID: 38477333Free PMC Article
Savige J, Renieri A, Ars E, Daga S, Pinto AM, Rothe H, Gale DP, Aksenova M, Cerkauskaite A, Bielska O, Lipska-Zietkiewicz B, Gibson JT
Clin J Am Soc Nephrol 2022 Nov;17(11):1697-1706. Epub 2022 Jun 8 doi: 10.2215/CJN.03120322. PMID: 35675912Free PMC Article
Savige J, Lipska-Zietkiewicz BS, Watson E, Hertz JM, Deltas C, Mari F, Hilbert P, Plevova P, Byers P, Cerkauskaite A, Gregory M, Cerkauskiene R, Ljubanovic DG, Becherucci F, Errichiello C, Massella L, Aiello V, Lennon R, Hopkinson L, Koziell A, Lungu A, Rothe HM, Hoefele J, Zacchia M, Martic TN, Gupta A, van Eerde A, Gear S, Landini S, Palazzo V, Al-Rabadi L, Claes K, Corveleyn A, Van Hoof E, van Geel M, Williams M, Ashton E, Belge H, Ars E, Bierzynska A, Gangemi C, Renieri A, Storey H, Flinter F
Clin J Am Soc Nephrol 2022 Jan;17(1):143-154. Epub 2021 Dec 20 doi: 10.2215/CJN.04230321. PMID: 34930753Free PMC Article
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016
McAdoo SP, Pusey CD
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1162-1172. Epub 2017 May 17 doi: 10.2215/CJN.01380217. PMID: 28515156Free PMC Article

Diagnosis

Albuquerque ALB, Dos Santos Borges R, Conegundes AF, Dos Santos EE, Fu FMM, Araujo CT, Vaz de Castro PAS, Simões E Silva AC
World J Pediatr 2023 Jul;19(7):619-634. Epub 2023 Feb 2 doi: 10.1007/s12519-023-00685-y. PMID: 36729281
Ponticelli C, Calatroni M, Moroni G
Autoimmun Rev 2023 Jan;22(1):103212. Epub 2022 Oct 14 doi: 10.1016/j.autrev.2022.103212. PMID: 36252931
Savige J, Lipska-Zietkiewicz BS, Watson E, Hertz JM, Deltas C, Mari F, Hilbert P, Plevova P, Byers P, Cerkauskaite A, Gregory M, Cerkauskiene R, Ljubanovic DG, Becherucci F, Errichiello C, Massella L, Aiello V, Lennon R, Hopkinson L, Koziell A, Lungu A, Rothe HM, Hoefele J, Zacchia M, Martic TN, Gupta A, van Eerde A, Gear S, Landini S, Palazzo V, Al-Rabadi L, Claes K, Corveleyn A, Van Hoof E, van Geel M, Williams M, Ashton E, Belge H, Ars E, Bierzynska A, Gangemi C, Renieri A, Storey H, Flinter F
Clin J Am Soc Nephrol 2022 Jan;17(1):143-154. Epub 2021 Dec 20 doi: 10.2215/CJN.04230321. PMID: 34930753Free PMC Article
Kashtan CE, Gross O
Pediatr Nephrol 2021 Mar;36(3):711-719. Epub 2020 Nov 6 doi: 10.1007/s00467-020-04819-6. PMID: 33159213
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016

Therapy

Ponticelli C, Calatroni M, Moroni G
Autoimmun Rev 2023 Jan;22(1):103212. Epub 2022 Oct 14 doi: 10.1016/j.autrev.2022.103212. PMID: 36252931
Warady BA, Pergola PE, Agarwal R, Andreoli S, Appel GB, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Kashtan CE, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Rheault MN, Silva AL, Stenvinkel P, Torra R, Chertow GM
Clin J Am Soc Nephrol 2022 Dec;17(12):1763-1774. Epub 2022 Nov 21 doi: 10.2215/CJN.02400222. PMID: 36411058Free PMC Article
Zhang Y, Böckhaus J, Wang F, Wang S, Rubel D, Gross O, Ding J
Pediatr Nephrol 2021 Sep;36(9):2719-2730. Epub 2021 Mar 27 doi: 10.1007/s00467-021-05040-9. PMID: 33772369Free PMC Article
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016
McAdoo SP, Pusey CD
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1162-1172. Epub 2017 May 17 doi: 10.2215/CJN.01380217. PMID: 28515156Free PMC Article

Prognosis

Chavez E, Goncalves S, Rheault MN, Fornoni A
Adv Kidney Dis Health 2024 May;31(3):170-179. doi: 10.1053/j.akdh.2024.02.004. PMID: 39004457
Albuquerque ALB, Dos Santos Borges R, Conegundes AF, Dos Santos EE, Fu FMM, Araujo CT, Vaz de Castro PAS, Simões E Silva AC
World J Pediatr 2023 Jul;19(7):619-634. Epub 2023 Feb 2 doi: 10.1007/s12519-023-00685-y. PMID: 36729281
Savige J, Renieri A, Ars E, Daga S, Pinto AM, Rothe H, Gale DP, Aksenova M, Cerkauskaite A, Bielska O, Lipska-Zietkiewicz B, Gibson JT
Clin J Am Soc Nephrol 2022 Nov;17(11):1697-1706. Epub 2022 Jun 8 doi: 10.2215/CJN.03120322. PMID: 35675912Free PMC Article
Nozu K, Nakanishi K, Abe Y, Udagawa T, Okada S, Okamoto T, Kaito H, Kanemoto K, Kobayashi A, Tanaka E, Tanaka K, Hama T, Fujimaru R, Miwa S, Yamamura T, Yamamura N, Horinouchi T, Minamikawa S, Nagata M, Iijima K
Clin Exp Nephrol 2019 Feb;23(2):158-168. Epub 2018 Aug 20 doi: 10.1007/s10157-018-1629-4. PMID: 30128941Free PMC Article
McAdoo SP, Pusey CD
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1162-1172. Epub 2017 May 17 doi: 10.2215/CJN.01380217. PMID: 28515156Free PMC Article

Clinical prediction guides

Savige J, Renieri A, Ars E, Daga S, Pinto AM, Rothe H, Gale DP, Aksenova M, Cerkauskaite A, Bielska O, Lipska-Zietkiewicz B, Gibson JT
Clin J Am Soc Nephrol 2022 Nov;17(11):1697-1706. Epub 2022 Jun 8 doi: 10.2215/CJN.03120322. PMID: 35675912Free PMC Article
Furlano M, Martínez V, Pybus M, Arce Y, Crespí J, Venegas MDP, Bullich G, Domingo A, Ayasreh N, Benito S, Lorente L, Ruíz P, Gonzalez VL, Arlandis R, Cabello E, Torres F, Guirado L, Ars E, Torra R
Am J Kidney Dis 2021 Oct;78(4):560-570.e1. Epub 2021 Apr 7 doi: 10.1053/j.ajkd.2021.02.326. PMID: 33838161
Savige J, Ariani F, Mari F, Bruttini M, Renieri A, Gross O, Deltas C, Flinter F, Ding J, Gale DP, Nagel M, Yau M, Shagam L, Torra R, Ars E, Hoefele J, Garosi G, Storey H
Pediatr Nephrol 2019 Jul;34(7):1175-1189. Epub 2018 Jul 9 doi: 10.1007/s00467-018-3985-4. PMID: 29987460
Kashtan CE, Ding J, Garosi G, Heidet L, Massella L, Nakanishi K, Nozu K, Renieri A, Rheault M, Wang F, Gross O
Kidney Int 2018 May;93(5):1045-1051. Epub 2018 Mar 16 doi: 10.1016/j.kint.2017.12.018. PMID: 29551517
McAdoo SP, Pusey CD
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1162-1172. Epub 2017 May 17 doi: 10.2215/CJN.01380217. PMID: 28515156Free PMC Article

Recent systematic reviews

Zeng M, Di H, Liang J, Liu Z
Nephrol Dial Transplant 2023 Oct 31;38(11):2485-2493. doi: 10.1093/ndt/gfad105. PMID: 37218713
Gomes AM, Lopes D, Almeida C, Santos S, Malheiro J, Lousa I, Caldas Afonso A, Beirão I
Int J Mol Sci 2022 Jun 30;23(13) doi: 10.3390/ijms23137276. PMID: 35806283Free PMC Article
Alwahaibi NY, Al Issaei HK, Al Dhahli BS
Saudi J Kidney Dis Transpl 2019 Jan-Feb;30(1):15-23. PMID: 30804262
Ziogas IA, Mylonas KS, Tsoulfas G, Spartalis E, Zavras N, Nikiteas N, Schizas D
Eur J Pediatr Surg 2019 Dec;29(6):487-494. Epub 2018 Dec 21 doi: 10.1055/s-0038-1676507. PMID: 30577043
Morzaria S, Westerberg BD, Kozak FK
J Otolaryngol 2005 Oct;34(5):297-303. doi: 10.2310/7070.2005.34501. PMID: 16181590

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