1. What is the genetic defect in Alport syndrome?
    • Abnormality in Type IV collagen alpha chains 3, 4 or 5
    • COL4A3 & 4 - Chr 2q35-7
    • COL4A5 & 6 - X Chr
  2. Where are type 4 collagen alpha 3,4 and 5 chains expressed?
    Basement membrane of glomerulus, skin basement membrane, lens capsule, and ? organ of Corti basememt membrane in cochlea
  3. How is Alport syndrome inherited?
    • X-linked - 80% of cases
    • AR - 15%
    • AD - 5%
  4. What are the histopathological changes of Alport syndrome?
    • light microscopy - focal increase in glomerular cellularity progressing to glomerulosclerosis
    • EM - thinning of BM, longitudinal splitting of lamina densa producing laminated appearance
    • Immunohistochem - absence or decreased staining of collagen IV alpha 3,4 and 5 chains in GBM
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  5. What is Alport syndrome?
    Inherited progressive form of glomerular disease often associated with sensorineural hearing loss and ocular abnormalities
  6. What are the clinical features of Alport syndrome?
    • Asymptomatic persistent microscopic haematuria
    • occasionally recurrent macroscopic haematuria
    • Proteinuria, HTN and progressive renal insufficiency progressing to ESRD by 16-35 yrs
    • Bilateral sensorineural hearing loss
    • Anterior lenticonus - sometimes associated with subcapsular cataracts
    • Bilateral white or yellow retinal granulations
    • Corneal dystrophy and erosion
    • Leiomyomatosis - resp, GI and female reproductive tracts
  7. What is the managment of Alport syndrome?
    • Blood pressure control - ACE inhibitors
    • Renal transplantation
  8. Which syndrome is antenatal hydronephrosis associated with?
    Trisomy 21
  9. What are the most common causes of antenatal hydronephrosis?
    • Transient 48%
    • Physiologic 15%
    • PUJ obstruction 11%
    • VUR 9%
    • Megaureter 4%
    • Multicystic dysplastic kidney 2%
    • Ureterocoele 2%
    • Posterior urethral valves 1%
  10. Which other congenital anomalies are associated with antenatal hydronephrosis?
    • VSD
    • Microcephaly
    • Omphalocoele
  11. Which causes of metabolic alkalosis are saline-responsive?
    • Vomiting
    • pyloric stenosis
    • congenital chloride diarrhoea
    • laxative abuse
    • diuretics
    • cystic fibrosis
  12. What is the mechanism behind non saline responsive metabolic alkalosis?
    • Mineralocorticoid excess
    • activation of RAA system, or hyperaldosteronism
  13. What is the genetic basis of autosomal recessive polycystic kidney disease?
    • Mutation in PKHD1 gene on Chr 6p21
    • encodes a large protein, fibrocystin
    • Defect in fibrocystin disrupts functioning of the renal cilia
  14. What are the renal manifestations of ARPKD?
    • Increased kidney size due to microcysts
    • Multiple cysts 3mm in diameter which radiate from medulla to cortex
    • Cysts are visible as pinpoint dots on the kidney surface
  15. What are the hepatic manifestations of ARPKD?
    • always associated with some degree of congenital hepatic fibrosis caused by ductal plate malformation of the developing biliary system
    • Some patients may have macroscopic dilations of the intrahepatic bile ducts in addition to congenital fibrosis = Caroli’s syndrome
  16. What are the clinical findings in a patient with ARPKD?
    • Severe cases may be diagnosed on antenatal US with enlarged kidneys bilaterally with increased echogenicity but no visible cysts. May be accompanied by oligohydramnios and absence of urine in bladder.
    • Hyponatremia (first few weeks of life) due to defective renal sodium handling
    • Reduced concentrating ability - maximal urine osmolality below 500 mosmol/kg
    • Decreased urinary acidification capacity - can lead to metabolic acidosis
    • Recurrent episodes of pyuria
    • Other findings include mild proteinuria, glucosuria, hyperphosphaturia, increased urinary excretion of magnesium, and urinary tract infections
    • Hypertension
  17. What is the genetic defect in thin basement membrane disease?
    • Heterozygous defect in COL4A3 or 4
    • Patients with TBMN can be considered "carriers" of autosomal recessive Alport syndrome
  18. What are the clinical characteristics of thin basement membrane disease?
    • Persistent or intermittent asymptomatic microscopic haematuria
    • Dysmorphic red cells and red cell casts on urine microsocpy
    • Uncommonly, episodes of macroscopic haematuria occur
    • blood pressure, renal function and urinary protein excretion usually normal - occasionally have non nephrotic proteinuria
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    • Minimal change disease
    • normal basement membrane
    • no immune deposits
    • characteristic widespread fusion of the epithelial cell foot processes
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    • Membranoproliferative (mesangiocapillary) glomerulonephritis
    • massive mesangial proliferation
    • diffuse thickening of the glomerular basement membrane
    • mesangial matrix expansion
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    • Post streptococcal glomerulonephritis
    • pathognomonic subepithelial deposits (D) with a semilunar, hump-shaped appearance. The humps sit on top of the glomerular basement membrane (GBM).
    • A neutrophil is attached to the denuded GBM, contributing to the glomerular inflammation. Neutrophil attraction requires the initial presence of subepithelial immune deposits so that complement chemoattractants have access to the systemic circulation.
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    • Can be seen in IgA nephropathy and lupus nephritis
    • Segmental areas of increased mesangial matrix and cellulatiry
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    • IgA nephropathy
    • Dense electron dense deposits in mesangial regions
    • GBM is normal
Card Set
Paediatric renal disorders