Inherited Disorders Flashcards
What is the most common life threatening hereditary disease?
Autosomal dominant polycystic disease
What mutations lead to ADPKD?
PKD1 (membrane receptor)
PKD2 (calcium channel)
Code for polycystin proteins which form a complex together
Name a substance that influences proliferation of epithelial cells
EGF
Where in the kidney is affected by ADPKD?
Tubules
What are the renal clinical features of ADPKD?
- decreased urine concentration
- chronic pain
- hypertension
- haematuria
- cyst infection
- renal failure
State some extra-renal features of ADPKD
Hepatic cysts - 10 years post renal cyst Intra-cranial aneurysm Cardiac disease (valvular disease) Diverticular Disease Hernias (abdominal and inguinal)
What is special about intracranial abscesses?
They run in families - are very rare and if present in a family screening measures are put in place
How is ADPKD diagnosed?
Radiologically - Ultrasound, CT, MRI (multiple bilateral cysts and renal enlargement)
Genetics - linkage and mutation analysis
If a parent has ADPKD what is the chance that the child has it?
50%
How is ADPKD managed?
Control hypertension
Hydration and proteinuria reduction
Cyst haemorrhage and infection control
What drug has been licenced for ADPKD recently?
Tolvapton - reduces cyst volume and progression
How can ADPKD and ARPKD be differentiated?
ARPKD has a stronger association with hepatic lesions, cysts appear from the collecting duct
What is the presentation of ARPKD?
Palpable kidneys, hypertension, recurrent UTIs, slow decline in GFR
How is Alports Syndrome inherited?
X linked
What is Alports syndrome?
Disorder in type IV collagen which leads to deficient collagenous matrix
What is the characteristic feature of alports?
Haematuria
State the extra-renal symptoms of alports
- sensorineural deafness
- ocular defects
- leiomyomatosis (oesophagus and genitalia)
What will renal biopsy of alports show?
Thickening of GBM
How is alports managed?
No specific treatment - treat BP/proteinuria may require dialysis or transplantation
What is Anderson Fabrys Disease?
Inborn erro in glycosphingolipid metabolism - X lined lysosomal storage disease
Where in the body does Anderson fabrys disease affect?
- kidneys
- liver
- lungs
- erythrocytes
What are the clinical features of Anderson fabrys disease?
- Renal failure
- Angiokeratomas
- Valve disease
- Stroke/acroparesthesia
- Psychiatric problems
What will biopsy of Anderson Fabrys disease show?
Lamellar inclusions in lysosomes
Other than biopsy what other investigations can be done on a patient with suspected Anderson Fabrys disease?
Skin biopsy, plasma/leukocyte aGAL activity
How is Anderson Fabrys Disease treated?
Replace fabryzyme and manage complications
Describe medullary cystic kidney
Rare autosomal dominant disease which leads to abnormal tubules and fibrosis
Where are the cysts in medullary cystic disease?
Corticomedullary junction and medulla
How is medullary cystic kidney diagnosed?
family history, CT, usually around 28 years old
What is the treatment for a medullary cystic kidney?
Transplantation
Describe medullary sponge kidney
Uncommon, sporadic inheritance leads to dilatation of collecting ducts
Why is medullary sponge kidney called that?
Sponge like appearance in severe disease
How is medullary sponge kidney diagnosed?
Excretion Urography - demarcates the calculi present in cysts
