Week 4 - H - Inheritied kidney disorders - P.K.D / Potter's, Alport's, Anderson-Fabry, Medullary cystic

Question 1

What are the two main types of polycystic kidney disease and which is more common?

Answer 1

Autosmoal dominant and autosomal recessive polycystic kidney disease

Autosomal dominant is more common

Question 2

Where do the cysts in PKD occur?

Answer 2

The cysts occur in the cortex and medulla of the kidneys therefor impeding function

Question 3

ADPKD is an important cause of ESRD

What stage of CKD is ESRD?

Answer 3

This is stage 5 - GFR <15 and patinet is on dialysis and prevelance is 0.1%

Question 4

What are the mutations in ADPKD? State which is more common?

Answer 4

85% is a mutation in PKD gene 1 on chromosome 16

15% is a mutation in PKD gene 2 on chromosome 4

Question 5

Why is genetic counselling important in a patinet with autosomal dominant polycystic kidney disease?

Answer 5

This is because the disease is autosomal dominant and therefore 50% of offsrping is likely to have the disease

Question 6

ADPKD presents in young adults usually What are the renal symptoms and signs?

Answer 6

Abdominal pain haematuria - rupture cyst

Big and palpable kidneys on balloting

Bilateral also

Progressive renal failure

Question 7

What happens to the urine production in ADPKD?

Answer 7

There is a reduced urine concentrating ability due to the cysts causing the kidney to be damaged and therfore the patient can experience enuresis

Question 8

What are extra renal signs of ADPKD? (ie what other organs are affected by the cysts and what is a really important other sign)

Answer 8

Hepatic and pacnreatic cysts usually on Ultrasound - usually non functioning

Ovarian cysts can also occur

Intra-cranial anuerysm - sub arachnoid haemorrhage - due to berry aneursym in circle of Willis rupturing

(big bilateral and berry aneurysms)

Question 9

What is the heart defects seen in ADPKD?

Answer 9

Tend to see mytral/aortic valve prolapse

Question 10

What is used for diagnosis of ADPKD?

Answer 10

Ultrasound examination to detect renal cysts

Question 11

If unsure of cysts on ultrasound, what is carried out?

Answer 11

Carry out CT scan to detect for cysts

Question 12

Autosomal dominant polycystic kidney disease in children can be difficult to differentiate from autosomal recessive PKD

If the ultrasound detects ______ when examining, how will this point more to ARPKD?,

Answer 12

On USS, the presence of suspicion of congenital hepatic fibrosis is associated with ARPKD

Question 13

In ADPKD, the urea and electrolytes need to be monitored What is the best option to control the blood pressure? What is the new treatment to reduce cyst volume and progression?

Answer 13

For the hypertension - prescribe ACEinhbitors

To reduce the cyst volume and progression - Tolvaptan

Question 14

What type of drug is tolvaptan?

Answer 14

it is a vasopressin antagonist

Question 15

If the patinet is in end stage renal failure, what is the treatment option?

Answer 15

Treat the patient with dialysis or transplant therapy

Question 16

What is the rarer form of polycytic kidney disease and what is the mutation?

Answer 16

This is autosomal recessive polycystic kidney disease - presents in children

Mutation in ARPKD is on the PKHD1 gene (polycystic kidney and hepatic disease 1) on chromosome 6

Question 17

What is the sydrome that can occur in newborns affected by polycystic kidney disease also seen in newborns with bilateral renal agenesis?

Answer 17

Potter’s syndrome - due to oligohydroamnios (deficiency of amniotic fluid)

Question 18

What are the features of potter’s syndrome?

Answer 18

Lung hypoplasia

Flat face and low set ears

Developmental defects of the limbs - due to oligohydroaminos

Question 19

5In ARPKD, there is bilateral renal involement with elongated cycts often causing medullary collecting duct dilatation What is ARPKD also associated with? (another congenital thing)

Answer 19

Congenital hepatic fibrosis which can lead to hypertension and hepatic cysts

Question 20

What is the clinical presentation of ARPKD?

Answer 20

Child presents with bilateral renal enlagrment

Is hypertensive, recurrent UTIs and kidneys are palpable

Question 21

In children with ARPKD, the investigation is done with a US/CT What percentage of children are expected to even reach dialysis?

Answer 21

Only 1/3rd of children reach dialsysis

Question 22

a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. What is this condition known as? 1-2% of patients end up with ESRD

Answer 22

This is Alport’s syndrome

Question 23

What is the muation of Alport’s syndrome and how is it passed on?

Answer 23

It is an X-linked inheritance where there is defect in the type IV collagen maturation

Question 24

What are the clincial defects of Alport’s syndrome?

Answer 24

Hameaturia

Sensorineural deafness

Ocular defects

Proteinuria - worse prognosis if this is here

Question 25

What is the ocular defect in Alport's syndrome known as?

Answer 25

Anterior lenticonus - they patient has a misshapen lens where the lens protrudes into the anterior chamber of the eye

Question 26

When a patinet presents with haematuria and sensorineural deafness, Alport's is suspected What is the test carried out?

Answer 26

Carry out a renal biopsy which shows variable thickness glomerular basement membrane which is a charcteristic feature

Question 27

What is given to control the preoteinuria and blood pressure in Alport's?

Answer 27

Give ACE inhibtor In patients progressing to ESRD - dialysis and transplantation are considered

Question 28

X linked lysosomal storage disease with Inborn error of glycosphingolipid metabolism What is the deificency in and hwat is the disease?

Answer 28

Anderosn-Fabry's disease - deficiency of a-galactosidaseA

Question 29

What are the organs affected by anderson-Fabry's disase?

Answer 29

The kidneys, livers, lungs and erythrocytes

Question 30

Run over again, what is Anderson'fabry's disease?

Answer 30

It is an X lnked inheritance a-galactosidase A deficiecny causing in error in lysosomal storage with an inborn error of glycosphingolipid metabolism

Question 31

How is Anderson-Fabry's disease diagnosed?

Answer 31

It is diagnosed by measuring a-GAL A or Renal or skin biopsy

Question 32

What are the clinical features of Anderson-Fabry's disease?

Answer 32

Renal failure Cutaenous lesions Cardiomyopathy / valvular disease Stroke

Question 33

What are the cutaneous lesions seen in Aderson-Fabry's disease known as?

Answer 33

These cutaneous lesions are known as angiokeratomas

Question 34

What do angiokertomas look like?

Answer 34

They look like small red/blue papules on the skin

Question 35

What is the treatmnet of Anderson-Fabry's disease?

Answer 35

Treat with enzyme replacement therapy - fabryzyme (man-made alpha-glactosidase A)

Question 36

One more time what is the defect in Anderson-Fary's disease? What is wrong in Alport's disease?

Answer 36

Anderson Fabry - Xlinked lysosomal storage disease with an inborn error of glycosphingolipid metabolsim (deficiency of alpha-galactosidase A) Alport's - defect in type IV collagen maturation - leads to haematuria, sensorinerual deafness, ocular defects (anterior leticnus) and proteinuria if severe

Question 37

Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts causing enal fibrosis What is this disorder?

Answer 37

This is medullary cystic disease

Question 38

What does the parenchymal fibrosis due to the cysts result in? (size and function of the kidneys)

Answer 38

This results in shrunken kidneys and renal failure as the kidneys lose their ability to concentrate the urine

Question 39

What are symptoms of medullary cystic kidney disease? What does PKD have that this does not as symptoms?

Answer 39

Medullary - polyuria, polydispia, enuresis PKD will also have a heavy felling in the back and abdominal pain with haematuria

Question 40

Medullary cystic disease is diagnosed by CT scan, what is the age of presentation and what is the treatment?

Answer 40

Roughly 28 years and renal transplant is treatment of choice

Question 41

Patinet presents with sensorineural loss, haematuria and proteinuria What is the other clinical feature? What is the disease? What is the treatment? What is the defect?

Answer 41

Patinet has Alport's syndrome Also associated with anterior leticonus (bilateral here) Defect in type IV collagen maturation - Xlinked Treatment is using ACEinhibtors