Renal Heritable Disorders AB

Question 1

Bartter’s syndrome - what is the mode of inheritance?

Answer 1

Autosomal recessive

Question 2

Bartter’s syndrome - what is the BP?

Answer 2

Normal BP

Question 3

Bartter’s syndrome - what is the defect?

Answer 3

Na/K/2CL channel in Loop of Henle

Like loop diuretics

Question 4

Bartter’s syndrome - what are the renin and aldosterone levels?

Answer 4

Increased renin, increased aldosterone

Question 5

Bartter’s syndrome - is the urine prostaglandin E level increased or decreased?

Answer 5

Increased

Question 6

Bartter’s syndrome - what is the typical presentation?

Answer 6

Neonatal presentation

Polyuria, polydipsia

Question 7

Gitelman syndrome - what is the mode of inheritance?

Answer 7

Autosomal recessive

Question 8

Gitelman syndrome - what is the BP?

Answer 8

Normal BP

Question 9

Gitelman syndrome - what is the defect?

Answer 9

Na/Cl channel in DCT causing salt wasting

Like Thiazide diuretics

Question 10

Gitelman syndrome - what are the biochemical abnormalities?

Answer 10

Hypokalaemia
Metabolic alkalosis
Hypomagnesaemia

HYPOcalciuria (like Thiazides)

Increased renin, increased aldosterone

Question 11

Bartter’s syndrome - what are the biochemical abnormalities?

Answer 11

Hypokalaemia +/- hypomagnesaemia
Metabolic alkalosis

HYPERcalciuria

Increased renin, increased aldosterone

Question 12

Pseudohypoaldosteronism type 2 - what is the mode of inheritance?

Answer 12

Autosomal dominant

Question 13

Pseudohypoaldosteronism type 2 - what is the typical presentation?

Answer 13

Hypertension in 2nd/3rd decade

Normal anion gap acidosis

Question 14

Pseudohypoaldosteronism type 2 - what are the biochemical abnormalities?

Answer 14

Hyperkalaemia
Hypercalciuria
High aldosterone levels
Normal anion gap acidosis

The opposite to Thiazides (e.g. opposite of Gitelman’s)

Question 15

Autosomal dominant PCKD - what are the genetic mutations?

Answer 15

PCKD1 - Ch 16

PCKD2 - Ch 4

Question 16

Autosomal recessive PCKD - what is the genetic mutation?

Answer 16

PKHD1 - Ch 6

Encodes for fibrocystin

Question 17

Tuberous sclerosis - what are the genetic mutations?

Answer 17

TSC1 or TSC2 genes

Question 18

Tuberous sclerosis - what is the mode of inheritance?

Answer 18

Autosomal dominant

Question 19

Tuberous sclerosis - what are the renal manifestations?

Answer 19

Kidney cysts
Angiomyolipomas (75%)
Renal cell carcinoma (1-2%)

Non-renal manifestations: facial angiofibromas, hypomelanotic macules, retinal hamartomas, dental abnormalities

Question 20

Alport syndrome - what is the mode of inheritance?

Answer 20

X-linked - 80%
Autosomal recessive - 15%
Autosomal dominant - 5%

Question 21

Alport syndrome - clinical presentation?

Answer 21

Sensorineural hearing loss
Ocular abnormalities
Microscopic haematuria
Family history

Late: proteinuria, hypertension CKD

Question 22

Alport syndrome - when do patients usually develop ESKD?

Answer 22

ESKD between late teens and fourth decade of life

Question 23

Alport syndrome - what is the underlying pathology?

Answer 23

Mutation in genes that code type IV collagen

Question 24

Alport syndrome - what is the treatment?

Answer 24

No specific therapies.

Kidney transplantation is the optimal treatment for ESKD

No risk of disease recurrence but 5% develop anti-GBM antibody disease after transplantation

Question 25

Medullary cystic kidney disease - what is the mode of inheritance?

Answer 25

Autosomal dominant

Rare

Question 26

Medullary cystic kidney disease - what is the underlying pathology?

Answer 26

Mutation in gene for uromodulin, also called Tamm-Horsfall mucoprotein

(Causative mutation unknown)

Question 27

Medullary cystic kidney disease - what are the clinical manifestations?

Answer 27

Impaired renal function
Mild urinary concentrating defects
Minimal proteinuria
Benign urinary sediment

Remember: misnomer - you usually can’t see cysts!

Question 28

Thin glomerular basement membrane disease (aka familial haematuria) - what is the underlying pathology?

Answer 28

A set of heterogenous conditions that result in haematuria

Some are heterozygous mutations that encode for type IV collagen

Question 29

Thin glomerular basement membrane disease - what is the prevalence?

Answer 29

Up to 5% of the population may be affected

Question 30

Thin glomerular basement membrane disease - what is the prognosis?

Answer 30

Long term prognosis is excellent, with rare progression to CKD

Question 31

Fabry disease - what is the mode of inheritance?

Answer 31

Rare X-linked disorder

Question 32

Fabry disease - what is the underlying pathology?

Answer 32

Disorder of alpha-galactosidase A deficiency,an error of the glycosphingolipid pathway

Question 33

Fabry disease - what is the typical presentation?

Answer 33

Young men with urinary concentration defects, proteinuria or CKD

Also premature coronary artery disease, severe neuropathic pain, telangiectasias and agiokeratomas

Question 34

Fabry disease - what is the treatment?

Answer 34

Screen family members

Enzyme replacement with recombinant human alpha-galactosidase A is effective

Question 35

Liddle syndrome - what is the mode of inheritance?

Answer 35

Rare autosomal dominant

Question 36

Liddle syndrome - what are the characteristic features?

Answer 36

Hypokalaemia
Metabolic alkalosis
Early onset hypertension
Decreased renin and aldosterone

Question 37

Liddle syndrome - what is the underlying pathology?

Answer 37

Increased number of sodium channels in the collecting ducts - unable to catabolise sodium channels

Similar to mineralocorticoid excess / licorice

Question 38

Liddle syndrome - what is the treatment?

Answer 38

Amiloride and triamterene (inhibits sodium uptake through epithelial sodium channels)