Genetic Diseases Affecting the Kidney

Question 1

Describe the typical presentation of AD polycystic kidney disease [8]

Answer 1

1. can be incidental finding on USS
2. hypertension
3. impaired renal function (low eGFR)
4. loin pain
5. haematuria
6. enlargement of cyst → cyst infection → cyst rupture

Question 2

How do you diagnose ADPKD taking into account family history and ages of patients? [4]

Answer 2

1. if family history is present, ultrasound will be done at age 21
   
   • age 15-30 → 2 unilateral or bilateral cysts
   • age 30-59 → 2 cysts in each kidney
   • age >60 → 4 cysts in each kidney
2. if no family history, then diagnosis is made on the presence of:
   
   • 10 or more cysts in both kidneys
   • renal enlargement
   • liver cysts

Question 3

What are the management options for APKD? [6]

Answer 3

1. Management is supportive
2. Early detection and management of blood pressure
3. Treat complications
4. Manage extra-renal associations
5. Prepare for renal replacement therapy
6. Recent development in tolvaptan - vasopressin V2 receptor antagonist

Question 4

Alport’s Syndrome

1. genetic basis? [1]
2. presentation? [2]
3. what molecule does it mainly affect? [1]
4. histological features? [2]
5. complications? [3]

Answer 4

1. usually x-linked
2. presents with deafness and renal failure (can affect other organs including eyes too)
3. affects collagen in basement membrane
4. abnormally split and laminated GBM
5. complications:
   
   • microscopic haematuria
   • proteinuria
   • end stage renal failure
   • most patients will end up on dialysis

Question 5

Fabry’s Disease

1. genetic basis? [1]
2. definition? [1]
3. complications? [6]
4. diagnosis? [2]
5. management? [1]

Answer 5

1. X-linked storage disorder
2. Alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
3. complications:
   
   • Gb3 accumulates in glomeruli, particularly podocytes
   • this causes:
     
     • proteinuria
     • end stage renal failure (ESRF)
   • neuropathy, cardiac and skin features also occur
4. diagnosis:
   
   • measure alpha-Gal A activity in leukocytes
   • renal biopsy - inclusion bodies of G3b
5. management:
   
   • enzyme replacement therapy