Inborn Errors of Renal Tubular Transport

Question 1

Renal Tubular Acidosis with occular abnormalities

Inheritance pattern

Answer 1

AR

Question 2

SLC4A4 encodes

Answer 2

3 variants of electrogenic kidney type Na/HCO₃ co transporter

NBCe1

Question 3

NBCe1 location and function

Answer 3

Found in basolateral membrane of PT and is responsible for transcellular bicarbonate reabsorption

Question 4

NbCe1 Mutation consequences

Answer 4

Impaired bicarb reabsortpion→ Proximal Renal Tubular Acidosis

Question 5

Reason for ocular disturbances in NBce1 mutation

Answer 5

Imparied bicarb effluc by corneal endothelium→ increased pH in stroma→Ca deposition→BAND KERATOPATHY

PLUS: Glaucoma, cataract, mntal retardation, impaired pancreatic function, poor dentition

Question 6

Cystineurea

Pathophysiology

Answer 6

Inadeuquete cystiene reabsorption in PCT→ increased conc. in urine→cysteine percipitates @ high conc. when pH<7→ present with microscopic hexagonal crystals in urine (kidney, ureter, bladder)

Question 7

Cystineurea

Genes involved

Answer 7

1. SLC3A1→encodes rBAT a transport protein involved in high affinity Na independent transport of basic and dibasic neural aa
2. SLC7A9→BAT1 (specificity and functional unit)

rBAT and BAT form a hetrodimer in brush border of PT and enterocyte to rebasorb cystine.

Question 8

Mutation in

SLC3A1

Answer 8

Cystinurea Type A

NOTE: If heterozygous→no effect

Question 9

Mutation in

SLC7A9

Answer 9

Cystineurea Type B

NOTE: If heterozygous→ moderate increase in dibasic aa

Question 10

Mutation in SLC3A1 and SLC7A9

Answer 10

Cystineurea type AB

Question 11

Compound mutations in terms of cysteinurea

Answer 11

Underlying deffect does not affect severity

Question 12

Lysinuric Protein Intolerance

genes involved

Answer 12

SLC7A7→mediates trabsport of dibasic aa to basolateral compartment from intracellular compartment

Question 13

Presentation of pt with Lysinuric Protein Intolerance

Answer 13

presents with LOW arginine and ornithine (involved in urea cycle)→HYPERAMMONEMIC

NO stones

Question 14

Treatment of pt with Lysinuric Protein Intolerance

Answer 14

• Restrict proteins
• Citrulline supplementation

Question 15

Hartnup Disorder

Genes involved

Answer 15

SLC6A19→encodes low affinity transporter of neutral aa drom lumen into cell

Question 16

Hartnup Disorder

characterized by

Answer 16

ISOLATED neutral aminoacidurea

Tryptophan def.→decreased niacin, serotonin synthesis→PELLAGRA

Question 17

Why are hartnup pt usually asymptomatic

Answer 17

cuz high protein diet

Question 18

How are symptomatic hartup pt treated

Answer 18

Niacin supplements

Question 19

Familial Renal Glucosuria

Answer 19

• Bening
• NO long term renal comploications
• 170g/day causing osmotic diuresis→frequent UTI and nocturnal eneuresis
• If starved, low fluid esp during pregnancy→KETOSIS and dehydration
• some→mild tubular defects (selective/genrealzied amminoacidurea and hyperCaurea)

Question 20

Familial Renal Glucosuria

gene involved

Answer 20

SLC5A2→SGLT2→Major Na Glu reabsorber in KIDNEY ONLY (1:1)

NOTE: no clear genotype phenotype relationship

• homozygous, compound heterozygous→SEVERE
• heterozygous→Slight glucosuria

Question 21

Fanconi- Bickel Syndrome

Answer 21

• RARE
• GLYCOGEN STORAGE DISEASE
• Hepatomegaly, renal fanconi, sevrely stunted growth, cataracts?

Question 22

Fanconi- Bickel Syndrome

Therapy

Answer 22

• Ketogenic diet
• Complex carbs

Question 23

Fanconi- Bickel Syndrome

gene involved

Answer 23

SLC2A2→GLUT 2

• glucose transport across hepatocyte plasma membrane
• uptake of glucose by ß cells (glucose sensning mechanism)
• transcellular glucose transport in enterocytes and tubular cells

NOTE:

• biallelic mutations found with no clear genotype phenotupe relationship
• heterozygous missense mutation only of GLUT2 mutations causes isolated renal glucosurea

Question 24

Vitamin B12 Malabsorption with Proteinurea

Answer 24

• Megaloblastic anemia
• in childhood→ anemia, recurrent infections, failure to thrive and neurological damage
• 50%→ isolated mild to moderate proteinurea with no tubular, glmoerular pattern and normal kidney function
• SUBCLINICAL: atherosclerosis, dementia, osteoperosis in elderly
• NOT DUE to decrease IF but stil cant transport B12 across intestinal membrane

Question 25

Vitamin B12 Malabsorption with Proteinurea

Therapy

Answer 25

Life long B12 parenteral infusion to reverse EXRTRARENAL manifestations

Question 26

Vitamin B12 Malabsorption with Proteinurea

Mutations

Answer 26

CUBN→CUBULIN
AMN→AMNIONLESS→ urogenital malformations since involved in gastrulation

imserald grabeck