Skip to main content
SpringerLink
Log in

Glomerular basement membrane lipidosis in Alagille syndrome

  • Brief Report
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Alagille syndrome is characterized by a paucity of interlobular bile ducts with chronic cholestasis, cardiac, skeletal, and eye abnormalities and is associated predominantly with JAG1 mutations. Various renal abnormalities have been sporadically described. The classic renal histopathology described in Alagille syndrome is mesangiolipidosis, with lipid deposits predominately confined to the mesangium and minimal deposition within the glomerular basement membrane (GBM). We report a 5-year-old girl with Alagille syndrome who presented with persistent subnephrotic proteinuria and renal tubular acidosis. A renal biopsy showed GBM irregularities (mimicking membranous glomerulonephritis), mesangial sclerosis, and focal segmental glomerulosclerosis (FSGS) on light microscopy. Electron microscopy revealed few lipid inclusions within the mesangium but extensive inclusions along the GBM. These findings are mostly consistent with those reported previously in Alagille syndrome. However, the histologic distribution of lipid vacuoles is seemingly reversed in this patient and is uniquely accompanied by FSGS, emphasizing the spectrum of renal histopathology seen in Alagille syndrome. The proteinuria observed in this patient is likely attributed to significant GBM lipid deposition, which over time may contribute to the development of FSGS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommergues JP (1987) Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 110(2):195–200

    Article  CAS  PubMed  Google Scholar 

  2. Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA (1999) Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29(3):822–829

    Article  CAS  PubMed  Google Scholar 

  3. McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB (2006) NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 79(1):169–173

    Article  CAS  PubMed  Google Scholar 

  4. Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez P, Piccoli DA, Krantz ID, Spinner NB (2006) Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 27(5):436–443

    Article  CAS  PubMed  Google Scholar 

  5. Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, Qi M, Trask BJ, Kuo WL, Cochran J, Costa T, Pierpont ME, Rand EB, Piccoli DA, Hood L, Spinner NB (1997) Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 16(3):243–251

    Article  CAS  PubMed  Google Scholar 

  6. McCright B (2003) Notch signaling in kidney development. Curr Opin Nephrol Hypertens 12(1):5–10

    Article  CAS  PubMed  Google Scholar 

  7. Habib R, Dommergues JP, Gubler MC, Hadchouel M, Gautier M, Odievre M, Alagille D (1987) Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia). Pediatr Nephrol 1(3):455–464

    Article  CAS  PubMed  Google Scholar 

  8. Russo PA, Ellis D, Hashida Y (1987) Renal histopathology in Alagille’s syndrome. Pediatr Pathol 7(5–6):557–568

    Article  CAS  PubMed  Google Scholar 

  9. Martin SR, Garel L, Alvarez F (1996) Alagille’s syndrome associated with cystic renal disease. Arch Dis Child 74(3):232–235

    Article  CAS  PubMed  Google Scholar 

  10. Hirai H, Santo Y, Kogaki S, Kurotobi S, Etani Y, Mushiake S, Nakatsuchi Y, Nakajima S, Ozono K (2005) Successful stenting for renal artery stenosis in a patient with Alagille syndrome. Pediatr Nephrol 20(6):831–833

    Article  PubMed  Google Scholar 

  11. Jacquet A, Guiochon-Mantel A, Noel LH, Sqalli T, Bedossa P, Hadchouel M, Grunfeld JP, Fakhouri F (2007) Alagille syndrome in adult patients: it is never too late. Am J Kidney Dis 49(5):705–709

    Article  PubMed  Google Scholar 

  12. Chung-Park M, Petrelli M, Tavill AS, Hall PW 3rd, Henoch MS, Dahms BB (1982) Renal lipidosis associated with arteriohepatic dysplasia (Alagille’s syndrome). Clin Nephrol 18(6):314–320

    CAS  PubMed  Google Scholar 

  13. Rosenthal IM, Spellberg MA, Mc Grew EA, Rozenfeld IH (1961) Absence of interlobular bile ducts. Report of a case of probable intrahepatic bile duct agenesis with severe hypercholesterolemia, xanthomatosis, and glomerular lipid deposition. Am J Dis Child 101:228–237

    CAS  PubMed  Google Scholar 

  14. Harendza S, Hubner CA, Glaser C, Burdelski M, Thaiss F, Hansmann I, Gal A, Stahl RA (2005) Renal failure and hypertension in Alagille syndrome with a novel JAG1 mutation. J Nephrol 18(3):312–317

    CAS  PubMed  Google Scholar 

  15. Benoit G, Sartelet H, Levy E, Boule ME, Alvarez F, Abed L, Merouani A (2007) Mesangiolipidosis in Alagille syndrome-relationship with apolipoprotein A-I. Nephrol Dial Transplant 22(7):2072–2075

    Article  PubMed  Google Scholar 

  16. Faraggiana T, Churg J (1987) Renal lipidoses: a review. Hum Pathol 18(7):661–679

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L471, Portland, OR, 97239, USA

    Jessica Davis, Kay Larkin & Megan Troxell

  2. Department of Medicine, Division of Nephrology & Hypertension, Oregon Health & Science University, Portland, OR, USA

    Ryan Griffiths

  3. Department of Pediatrics, Division of Nephrology, Doernbecher Childrens Hospital, Oregon Health & Science University, Portland, OR, USA

    David Rozansky

Authors
  1. Jessica Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryan Griffiths
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kay Larkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Rozansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Megan Troxell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Megan Troxell.

Additional information

Jessica Davis and Ryan Griffiths contributed equally to the manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davis, J., Griffiths, R., Larkin, K. et al. Glomerular basement membrane lipidosis in Alagille syndrome. Pediatr Nephrol 25, 1181–1184 (2010). https://doi.org/10.1007/s00467-009-1426-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-009-1426-0

Keywords

Search

Navigation