Síndrome de Alport: reporte de caso y revisión.

Publicado

2015-01-01

Alport sindrome: Case report and literature review

Palabras clave:

Nefritis hereditaria, hematuria, proteinuria, síndrome de Alport (es)
Nephritis, hereditary, Hematuria, Proteinuria, Alport Syndrome (en)

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Autores/as

Jose Augusto Urrego-Díaz Departamento de Pediatría, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá, D. C., Colombia.
Guillermo Landinez-Millán Departamento de Pediatría, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá, D. C., Colombia.
Carlos Javier Lozano-triana Departamento de Pediatría, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá, D. C., Colombia. Unidad de Medicina Interna, Hospital de la Misericordia. Bogotá, D. C., Colombia.

Resumen (es)
Resumen (en)

Se presenta el caso de una paciente de 4 años de edad, con hermano gemelo dicigoto asintomático, hija de padres no consanguíneos y sin antecedentes familiares de enfermedad renal. Inicia su cuadro clínico con edemas y proteinuria severa como manifestación de un síndrome nefrótico primario de cambios mínimos; este se diagnosticó por biopsia renal y, en un principio, se manejó con esteroides. Su evolución no fue adecuada debido a múltiples recaídas que la clasiﬁcaron como síndrome nefrótico corticorresistente. Por ello, se requirió un cambio en su tratamiento y una segunda biopsia renal, cuyo resultado histológico sorprendió al grupo médico tratante porque los cambios en la membrana basal glomerular conﬁrmaban que se trataba de un Síndrome de Alport.

We present the case of a 4 year-old girl patient, with an asymptomatic dizygotic twin brother, child of non-consanguineous parents and with no family history of renal disease. Her clinical picture started with edema and severe proteinuria as manifestations of a minimal change nephrotic syndrome that was diagnosed by renal biopsy and initially treated with steroids. Her clinical course was complicated by multiple relapses that classified her as a patient presenting a steroid-resistant nephrotic syndrome, her treatment was changed and a second renal biopsy was needed. Histology outcome of biopsy surprised the treating medical group because changes in glomerular basal membrane revealed that it was in fact an Alport syndrome.

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Citas

Alport AC. Hereditary familial congenital haemorrhagic nephritis. Br Med J. 1927 [cited 2015 feb 12];1(3454):504-6. doi: http://doi.org/cqx6nk.

Kashtan CE. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore). 1999 [cited 2015 feb 12];78(5):338-60. doi: http://doi.org/fmtssz.

Barker DF, Pruchno CJ, Jiang X, Atkin CL, Stone EM, Denison JC, et al. A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. Am J Hum Genet. 1996;58(6):1157-65.

Gretz N, Broyer M, Brunner FP, Brynger H, Donckerwolcke RA, Jacobs C, et al. Alport's syndrome as a cause of renal failure in Europe. Pediatr Nephrol. 1987 [cited 2015 feb 12];1(3):411-5. doi: http://doi.org/ffd594.

Feingold J, Bois E, Chompret A, Broyer M, Gubler MC, Grünfeld JP. Genetic heterogeneity of Alport syndrome. Kidney Int. 1985 [cited 2015 feb 12];27(4):672-7. doi: http://doi.org/dq4m7n.

O'Neill WM, Atkin CL, Bloomer HA. Hereditary nephritis: a re-examination of its clinical and genetic features. Ann Intern Med. 1978 [cited 2015 feb 12];88(2):176-82. doi: http://doi.org/zr8.

Medeiros M, Fuentes Y, García P, Hernández A, Morán F, Velásquez L. Síndrome de Alport. Bol Med Hosp Infant Mex. 2008;65:331-40.

Heidet L, Arrondel C, Forestier L, Cohen-Solal L, Mollet G, Gutierrez B, et al. Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome. J Am Soc Nephrol. 2001;12(1):97-106.

Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, et al. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int. 2002 [cited 2015 feb 12];61(6):1947-56. doi: http://doi.org/fr8x7z.

Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, et al. Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 2007 [cited 2015 feb 12];71(12):1287-95. doi: http://doi.org/d3skt5.

Rheault MN. Women and Alport syndrome. Pediatr Nephrol. 2012 [cited 2015 feb 12];27(1):41-6. doi: http://doi.org/dsmf5p.

Bekheirnia MR, Reed B, Gregory MC, McFann K, Shamshirsaz AA, Masoumi A, et al. Genotype-phenotype correlation in X-linked Alport syndrome. J Am Soc Nephrol. 2010 [cited 2015 feb 12];21(5):876-83. doi: http://doi.org/bpf3x6.

Kashtan CE. Alport Syndrome and Thin Basement Membrane Nephropathy: Diseases Arising from Mutations in Type IV Collagen. Saudi J Kidney Dis Transpl. 2003 [cited 2015 feb 12];14(3):276-89.

Boyd CD, Toth-Fejel SE, Gadi IK, Litt M, Condon MR, Kolbe M, et al. The genes coding for human pro alpha 1(IV) collagen and pro alpha 2(IV) collagen are both located at the end of the long arm of chromosome 13. Am J Hum Genet. 1988 [cited 2015 feb 12];42(2):309-14.

Mariyama M, Zheng K, Yang-Feng TL, Reeders ST. Colocalization of the genes for the alpha 3(IV) and alpha 4(IV) chains of type IV collagen to chromosome 2 bands q35-q37. Genomics. 1992 [cited 2015 feb 12];13(3):809-13. doi: http://doi.org/dpb5rx.

Hostikka SL, Eddy RL, Byers MG, Höyhtyä M, Shows TB, Tryggvason K. Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome. Proc Natl Acad Sci U S A. 1990 [cited 2015 feb 12];87(4):1606-10. doi: http://doi.org/fxhqxh.

Myers JC, Jones TA, Pohjolainen ER, Kadri AS, Goddard AD, Sheer D, et al. Molecular cloning of alpha 5(IV) collagen and assignment of the gene to the region of the X chromosome containing the Alport syndrome locus. Am J Hum Genet. 1990 [cited 2015 feb 12];46(6):1024-33.

Kashtan CE. Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr Opin Pediatr. 2004 [cited 2015 feb 12];16(2):177-81. doi: http://doi.org/bnc79s.

Lemmink HH, Schröder CH, Monnens LA, Smeets HJ. The clinical spectrum of type IV collagen mutations. Hum Mutat. 1997 [cited 2015 feb 12];9(6):477-99. doi: http://doi.org/bz9rjs.

Longo I, Scala E, Mari F, Caselli R, Pescucci C, Mencarelli MA, et al. Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families. Nephrol Dial Transplant. 2006 [cited 2015 feb 12];21(3):665-71. doi: http://doi.org/cdgr6m.

Uzak AS, Tokgoz B, Dundar M, Tekin M. A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family. Genet Test Mol Biomarkers. 2013 [cited 2015 feb 12];17(3):260-4. doi: http://doi.org/zr9.

Wang Y, Sivakumar V, Mohammad M, Colville D, Storey H, Flinter F, et al. Clinical and genetic features in autosomal recessive and X-linked Alport syndrome. Pediatr Nephrol. 2014 [cited 2015 feb 12];29(3):391-6. http://doi.org/zsb.

Fallerini C, Dosa L, Tita R, Del Prete D, Feriozzi S, Gai G, et al. Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases. Clin Genet. 2014 [cited 2015 feb 12];86(3):252-7. doi: http://doi.org/zsc.

Heath KE, Campos-Barros A, Toren A, Rozenfeld-Granot G, Carlsson LE, Savige J, et al. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genet. 2001 [cited 2015 feb 12];69(5):1033-45. doi: http://doi.org/d5n2xx.

Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, et al. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol. 2000;11(4):649-57.

Kalluri R, Gattone VH, Hudson BG. Identification and localization of type IV collagen chains in the inner ear cochlea. Connect Tissue Res. 1998 [cited 2015 feb 12];37(1-2):143-50. doi: http://doi.org/ccgz4f.

Nielsen CE. Lenticonus anterior and Alport's syndrome. Acta Ophthalmol (Copenh). 1978 [cited 2015 feb 12];56(4):518-30. doi: http://doi.org/dgr5zp.

Perrin D, Jungers P, Grünfeld JP, Delons S, Noël LH, Zenatti C. Perimacular changes in Alport's syndrome. Clin Nephrol. 1980 [cited 2015 feb 12];13(4):163-7.

Teekhasaenee C, Nimmanit S, Wutthiphan S, Vareesangthip K, Laohapand T, Malasitr P, et al. Posterior polymorphous dystrophy and Alport syndrome. Ophthalmology. 1991 [cited 2015 feb 12];98(8):1207-15. doi: http://doi.org/zsd.

Thompson SM, Deady JP, Willshaw HE, White RH. Ocular signs in Alport's syndrome. Eye (Lond). 1987 [cited 2015 feb 12];1:146-53. doi: http://doi.org/c2brbt.

Burke JP, Clearkin LG, Talbot JF. Recurrent corneal epithelial erosions in Alport's syndrome. Acta Ophthalmol (Copenh). 1991 [cited 2015 feb 12];69(4):555-7. doi: http://doi.org/dhkghg.

Rhys C, Snyers B, Pirson Y. Recurrent corneal erosion associated with Alport's syndrome. Rapid communication. Kidney Int. 1997 [cited 2015 feb 12];52(1):208-11. doi: http://doi.org/dv7j4v.

Antignac C, Heidet L. Mutations in Alport syndrome associated with diffuse esophageal leiomyomatosis. Contrib Nephrol. 1996;117:172-82.

Mothes H, Heidet L, Arrondel C, Richter KK, Thiele M, Patzer L, et al. Alport syndrome associated with diffuse leiomyomatosis: COL4A5-COL4A6 deletion associated with a mild form of Alport nephropathy. Nephrol Dial Transplant. 2002 [cited 2015 feb 12];17(1):70-4. doi: http://doi.org/d73nhp.

Heidet L, Cohen-Solal L, Boye E, Thorner P, Kemper MJ, David A, et al. Novel COL4A5/COL4A6 deletions and further characterization of the diffuse leiomyomatosis-Alport syndrome (DL-AS) locus define the DL critical region. Cytogenet Cell Genet. 1997 [cited 2015 feb 12];78(3-4):240-6. doi: http://doi.org/dcktsm.

Rana K, Wang YY, Powell H, Jones C, McCredie D, Buzza M, et al. Persistent familial hematuria in children and the locus for thin basement membrane nephropathy. Pediatr Nephrol. 2005 [cited 2015 feb 12];20(12):1729-37. doi: http://doi.org/d9qg9w.

Massella L, Onetti Muda A, Faraggiana T, Bette C, Renieri A, Rizzoni G. Epidermal basement membrane alpha 5(IV) expression in females with Alport syndrome and severity of renal disease. Kidney Int. 2003 [cited 2015 feb 12];64(5):1787-91. doi: http://doi.org/dwksq9.

Patey-Mariaud de Serre N, Garfa M, Bessiéres B, Noël LH, Knebelmann B. Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients. Kidney Int. 2007 [cited 2015 feb 12];72(4):512-6. doi: http://doi.org/fxb9qt.

Kleppel MM, Santi PA, Cameron JD, Wieslander J, Michael AF. Human tissue distribution of novel basement membrane collagen. Am J Pathol. 1989;134(4):813-25.

Gubler MC, Knebelmann B, Beziau A, Broyer M, Pirson Y, Haddoum F, et al. Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. Kidney Int. 1995 [cited 2015 feb 12];47(4):1142-7. doi: http://doi.org/dvcb2z.

Gubler MC. Diagnosis of Alport syndrome without biopsy? Pediatr Nephrol. 2007 [cited 2015 feb 12];22(5):621-5. doi: http://doi.org/bqxwcv.

Artuso R, Fallerini C, Dosa L, Scionti F, Clementi M, Garosi G, et al. Advances in Alport syndrome diagnosis using next-generation sequencing. Eur J Hum Genet. 2012 [cited 2015 feb 12];20(1):50-7. doi: http://doi.org/ftfdqm.

Kashtan CE. Familial hematuria. Pediatr Nephrol. 2009 [cited 2015 feb 12];24(10):1951-8. doi: http://doi.org/ft28vg.

Kaito H, Nozu K, Iijima K, Nakanishi K, Yoshiya K, Kanda K, et al. The effect of aldosterone blockade in patients with Alport syndrome. Pediatr Nephrol. 2006 [cited 2015 feb 12];21(12):1824-9. doi: http://doi.org/bqw8xp.

Giani M, Mastrangelo A, Villa R, Turolo S, Marra G, Tirelli AS, et al. Alport syndrome: the effects of spironolactone on proteinuria and urinary TGF-β1. Pediatr Nephrol. 2013 [cited 2015 feb 12];28(9):1837-42. doi: http://doi.org/zsf.

Desassis JF, Raats CJ, Bakker MA, van den Born J, Berden JH. Antiproteinuric effect of ciclosporin A in adriamycin nephropathy in rats. Nephron. 1997 [cited 2015 feb 12];75(3):336-41. doi: http://doi.org/b2j8z5.

Singh A, Tejani C, Tejani A. One-center experience with cyclosporine in refractory nephrotic syndrome in children. Pediatr Nephrol. 1999 [cited 2015 feb 12];13(1):26-32. doi: http://doi.org/cf85cg.

Charbit M, Gubler MC, Dechaux M, Gagnadoux MF, Grünfeld JP, Niaudet P. Cyclosporin therapy in patients with Alport syndrome. Pediatr Nephrol. 2007 [cited 2015 feb 12];22(1):57-63. doi: http://doi.org/c245bq.

McCoy RC, Johnson HK, Stone WJ, Wilson CB. Absence of nephritogenic GBM antigen(s) in some patients with hereditary nephritis. Kidney Int. 1982 [cited 2015 feb 12];21(4):642-52. doi: http://doi.org/fbv9v9.

Kashtan CE. Alport syndrome: renal transplantation and donor selection. Ren Fail. 2000 [cited 2015 feb 12];22(6):765-8. doi: http://doi.org/ct9xbh.