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Alport syndrome; hereditary nephropathy

Epidemiology: - males have worse prognosis Pathology: - signs & symptoms due to disruption of the basement membrane in the affected organ [2] - Goodpasture's antigen is absent - renal transplanted patients may develop anti-glomerular basement membrane disease - macrothrombocytopenia (MYH9-associated) Genetics: 1) autosomal dominant & X-linked inheritance - mutation in collagen type-4 alpha-5 (COL4A5) 2) autosomal dominant a) form with platelet defects associated with defects in MYH9 b) mutation in collagen type-4 alpha-3 (COL4A3)* 3) autosomal recessive a) mutation in collagen type-4 alpha-3 (COL4A3)* b) mutation in collagen type-4 alpha-4 (COL4A4)* 4) X-linked contiguous gene deletion syndrome associated with defects in KCNE1L * defects in COL4A3 & COL4A4 also associated with thin glomerular basement membrane disease Clinical manifestations: 1) glomerulonephritis progressing to end-stage renal disease (ESRD) by age 16-30 - females may have a benign course manifesting only as hematuria [6] 2) proteinuria, nephrotic syndrome 3) hypertension 4) high-frequency sensorineural hearing loss 5) ocular abnormalities a) anterior lenticonus b) cataracts c) maculopathy Laboratory: 1) complete blood count (CBC) - may show thrombocytopenia 2) peripheral blood smear: a) may show giant platelets b) may show eliptocytosis (X-linked form) 3) urinalysis: - proteinuria - microscopic hematuria 4) 24 hour urine protein: nephrotic range proteinuria 5) skin biopsy or renal biopsy can confirm diagnosis [2] 6) see ARUP consult [3] Manageemnt: - no specific therapy - blood pressure control with ACE inhibitor or ARB - renal transplantation for end-stage renal failure - Alport syndrome does not affect transpanted kidney [2] - 5% if transplant recipients develop anti-GBM Ab disease [2]

Interactions

disease interactions

Specific

Alport syndrome with mental retardation midface hypoplasia & elliptocytosis Alport syndrome/COL4A3 mutation associated X-linked Alport syndrome/COL4A5 mutation associated X-linked Alport syndrome/KCNE1L mutation associated

General

genetic disease of the central nervous system genetic disease of the kidney

Database Correlations

OMIM correlations

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 611
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. ARUP Consult: Alport Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/alport-syndrome
  4. Haas M. Alport syndrome and thin glomerular basement membrane nephropathy: a practical approach to diagnosis. Arch Pathol Lab Med. 2009 Feb;133(2):224-32 PMID: 19195966
  5. Gross O, Kashtan CE, Rheault MN et al Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome. Nephrol Dial Transplant. 2017 Jun 1;32(6):916-924. PMID: 27190345 Free PMC Article
  6. NEJM Knowledge+ Nephrology/Urology