Bartter Syndrome Gitelman Syndrome Liddle Syndrome Cystinuria Cysti
Inheritance Autosomal recessive Autosomal recessive Autosomal dominant Autosomal recessive Autosomal recessi
Affected part of Thick ascending limb of loop of Distal convoluted tubule DCT (Principal cells of Proximal convoluted Proximal convolute
nephron Henle conector tubule) tubule
Mutation Type I → NKCC → Na/K/2Cl SLC12A→ NCCT gene → Na/Cl Gain of function of ● rBAT / SLC3A1 All mutations in CT
(Type → gene → protein) Type II → KCNJ→ ROMK symporter SCNN1B & SCNN1G ● bAT1 / SLC7A9 cystinosin
Type III → CLCNKB → ClCkb ● Sensitive to thiazide genes → ENaC β and ɣ - Infantile: two se
Type IV → BSND → barttin diuretics subunits → prevents its alleles
- IVb → CLCNKA & CLCNKB → ubiquitination and - Adolescent: one
both channels degradation severely mutated a
Type V (A.D.) → CASR → CaSR - Adult: two mildly
Pathophysiology Dysfunction of protein disrupts the Failure to reabsorb Na and Cl → ↑ ENaC activity Failure to reabsorb Defective cystinos
electrochemical gradient → failure volume depletion. -↑Na retention → HTA COAL (cystine, ornithine, lysosomal transpo
to reabsorb Na, Cl, and K → Electrochemical disruption and ↓RAAS arginine, lysine) aa in the inside lysosomes a
negative lumen → failure to inhibits TRPM (Mg reabsorption) - ↑H excretion → PCT → if pH 5-7 → → crystals deposit
paracellularly reabsorb Mg and Ca and ↑ TRPV instead → ↑Mg and metabolic alkalosis cystine crystalizes damage → Fancon
↓Ca in urine - ↑K excretion
Electrolyte - Hypokalemia - Hypocalciuria - Hypokalemia Risk Factors: In Fanconi Sd: hyp
imbalances - Hypochloremia - Hypomagnesemia - Hypercalciuria hyponatremia, hyp
- Hypercalciuria → stones - Hypokalemia - Hypocitraturia bicarbonate
- Hyperuricosuria
Clinical features - ↑ RAAS activity Like Classic Bartter (milder) - Early-onset - Recurrent renal stones Infantile
● Normotensive - Diagnosed until late childhood hypertension (75% bilateral) - Multiorgan involv
● M. alkalosis or adulthood ● ↑ risk of cerebral - Renal colic - Metabolic acidos
● K depletion - ↑ RAAS activity ischemia - Hematuria - polyuria dehydra
- Nephrocalcinosis ● Normotensive ● Non-responsive - recurrent UTIs - vomiting, constip
Neonatal ( I, II & IV) ● M. alkalosis to tx Complications - Loss of appetite &
- Fetal polyuria ● K depletion - ↓K: - HTA - Salt & spicy food
● Polyhydramnios (24-30 w) - Polyuria ● Cramps - Renal insufficiency - Febrile episodes,
● FTT - FTT → due to ↑PGE ● Weakness - ESRD - Progression to:
● Fluid loss production ● muscle pain Associated symptoms ● ESRD (at 7
- Preterm delivery - Developmental delays ● Fatigue - Retinitis pigmentosa ● Blindness &
- Dysmorphic facies & strabismus - Salt craving ● Constipation - Hemophilia ● Cerebral ca
- Types IV & IVb → deafness - Cramps & muscle weakness ● Palpitations - Muscular dystrophy ● Thyroid ins
Classic (III) - <2 y.o. - Hereditary pancreatitis Adolescent
- Polyuria - Diagnosed by ag
- FTT → due to ↑PGE production - Only kidneys and
Inheritance Autosomal recessive Autosomal recessive Autosomal dominant Autosomal recessive Autosomal recessi
Affected part of Thick ascending limb of loop of Distal convoluted tubule DCT (Principal cells of Proximal convoluted Proximal convolute
nephron Henle conector tubule) tubule
Mutation Type I → NKCC → Na/K/2Cl SLC12A→ NCCT gene → Na/Cl Gain of function of ● rBAT / SLC3A1 All mutations in CT
(Type → gene → protein) Type II → KCNJ→ ROMK symporter SCNN1B & SCNN1G ● bAT1 / SLC7A9 cystinosin
Type III → CLCNKB → ClCkb ● Sensitive to thiazide genes → ENaC β and ɣ - Infantile: two se
Type IV → BSND → barttin diuretics subunits → prevents its alleles
- IVb → CLCNKA & CLCNKB → ubiquitination and - Adolescent: one
both channels degradation severely mutated a
Type V (A.D.) → CASR → CaSR - Adult: two mildly
Pathophysiology Dysfunction of protein disrupts the Failure to reabsorb Na and Cl → ↑ ENaC activity Failure to reabsorb Defective cystinos
electrochemical gradient → failure volume depletion. -↑Na retention → HTA COAL (cystine, ornithine, lysosomal transpo
to reabsorb Na, Cl, and K → Electrochemical disruption and ↓RAAS arginine, lysine) aa in the inside lysosomes a
negative lumen → failure to inhibits TRPM (Mg reabsorption) - ↑H excretion → PCT → if pH 5-7 → → crystals deposit
paracellularly reabsorb Mg and Ca and ↑ TRPV instead → ↑Mg and metabolic alkalosis cystine crystalizes damage → Fancon
↓Ca in urine - ↑K excretion
Electrolyte - Hypokalemia - Hypocalciuria - Hypokalemia Risk Factors: In Fanconi Sd: hyp
imbalances - Hypochloremia - Hypomagnesemia - Hypercalciuria hyponatremia, hyp
- Hypercalciuria → stones - Hypokalemia - Hypocitraturia bicarbonate
- Hyperuricosuria
Clinical features - ↑ RAAS activity Like Classic Bartter (milder) - Early-onset - Recurrent renal stones Infantile
● Normotensive - Diagnosed until late childhood hypertension (75% bilateral) - Multiorgan involv
● M. alkalosis or adulthood ● ↑ risk of cerebral - Renal colic - Metabolic acidos
● K depletion - ↑ RAAS activity ischemia - Hematuria - polyuria dehydra
- Nephrocalcinosis ● Normotensive ● Non-responsive - recurrent UTIs - vomiting, constip
Neonatal ( I, II & IV) ● M. alkalosis to tx Complications - Loss of appetite &
- Fetal polyuria ● K depletion - ↓K: - HTA - Salt & spicy food
● Polyhydramnios (24-30 w) - Polyuria ● Cramps - Renal insufficiency - Febrile episodes,
● FTT - FTT → due to ↑PGE ● Weakness - ESRD - Progression to:
● Fluid loss production ● muscle pain Associated symptoms ● ESRD (at 7
- Preterm delivery - Developmental delays ● Fatigue - Retinitis pigmentosa ● Blindness &
- Dysmorphic facies & strabismus - Salt craving ● Constipation - Hemophilia ● Cerebral ca
- Types IV & IVb → deafness - Cramps & muscle weakness ● Palpitations - Muscular dystrophy ● Thyroid ins
Classic (III) - <2 y.o. - Hereditary pancreatitis Adolescent
- Polyuria - Diagnosed by ag
- FTT → due to ↑PGE production - Only kidneys and
