Ans: (c) Bartter syndromeRef: Nelson Textbook of Pediatrics, 20th edition, Page 2534BARTTER SYNDROME (AUTOSOMAL RECESSIVE)Clinical Subtypes:Antenatal Bartter syndrome (Hyperprostaglandin E syndrome):Mutations-genes that encode the sodium potassium 2 chloride transporter NKCC2 (the site of action of furosemide) orThe luminal potassium channel ROMK - cause neonatal Bartter syndrome.Present with polyhydramnios, salt wasting and severe dehydration.Classic Bartter syndrome:Defects-genes that produce the basolateral chloride channel CIC-KbPresents milder in childhood with failure to thrive and a history of recurrent episodes of dehydration. PathogenesisDefect in sodium, chloride and potassium transport in the ascending loop of HenleHypokalemic metabolic alkalosis with hypercalciuria (similar to chronic loop diuretic use)The loss of sodium and chloride, with resultant volume contraction, stimulates the renin/angiotensin 11/ aldosterone axis.Aldosterone promotes sodium uptake and potassium secretion, exacerbating the hypokalemia.It also stimulates hydrogen ion secretion distally, worsening the metabolic alkalosis. Hypokalemia stimulates prostaglandins, which further activate the renin/angiotensin ll/aldosterone axis.Clinical Manifestations In Smaller ChildrenConsanguinity with history of polyhydramnios.Triangular facies, protruding ears, large eyes with strabismus and drooping mouth.In Older ChildrenHistory of recurrent episodes of dehydration, failure to thrive, Hypokalemic metabolic alkalosis, Urinary calcium, potassium and sodium levels - elevatedSerum renin, aldosterone and prostaglandin E levels - elevated (antenatal form)Blood pressure is usually normal, except in antenatal form - have severe salt wastingRenal function is typically normal, Ultrasound shows Nephrocalcinosis, due to hypercalciuria.Diagnosis - Based clinical presentation + laboratory findings.(Severe hypokalemia, usually <2.5mmol/L, with metabolic alkalosis. Hypercalciuria is typical)Differential Diagnosis:1. Diuretic abuse.2. Chronic vomiting - Measurement of urinary chloride (elevated - Bartter syndrome and low in patients - chronic vomiting).Treatment and PrognosisPrevent dehydration and maintaining nutritional status.Correcting hypokalemia (at very high doses)Sodium supplementation - Infants and young children.Indomethacin, a prostaglandin inhibitor, may also be effective.Long-term prognosis is generally good.Chronic hypokalemia, nephrocalcinosis and chronic indomethacin therapy can lead to chronic interstitial nephritis and chronic renal failure.GITELMAN SYNDROME (AUTOSOMAL RECESSIVE)Causes hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia.PathogenesisDefects - in sodium chloride co-transporter NCCT, present in the distal convoluted tubule (resembles chronic thiazide diuretic use).Clinical ManifestationsPresent late in childhood with history of recurrent muscle cramps and spasms due to hypomagnesemia.No history of recurrent episodes of dehydration.Biochemical abnormalities include hypokalemia, metabolic alkalosis and hypomagnesemia.The urinary calcium level is usually very low and urinary magnesium level is elevated.Prostaglandin E secretion, Renin and aldosterone levels - normal.Diagnosis - Adolescent - with hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Treatment - Correcting hypokalemia and hypomagnesemia.Liddle Syndrome:In collecting duct - gain of function mutations of the gene coding (epithelial sodium channel)Causes an inherited form of hypertension with hypokalemia and suppressed aldosteroneLoss of function mutations - pseudo hypoaldosteronism (severe sodium wasting and hyperkalemia).X (RECESSIVE)-linked nephrolithiasis (Dent disease)Mutations in the gene - voltage-gated chloride channel CLN5 (present throughout the nephron)Characterized by recurrent stone formation and progression to Fanconi syndrome.In loop of Henle - activating (severe hypoparathyroidism) and inactivating mutations (hyperparathyroidism) in the calcium receptor gene (which mediates parathyroid hormone-induced calcium uptake).ALPORT SYNDROME (AS) - (HEREDITARY NEPHRITIS)X-linked disease (85%) - Mutations in the genes coding for type IV collagen (gene - major component of basement membranes).Autosomal recessive - mutations in the COL4A3 and COL4A4 genes on chromosome 2Autosomal dominant form also occurs.Clinical Manifestations Renal manifestations:Asymptomatic intermittent microscopic hematuria.Recurrent episodes of gross hematuria occurring 1-2 days after an upper respiratory infectionProteinuria - frequently seen in males but may be absent in females.Progressive proteinuria can be severe enough to cause nephrotic syndrome.Extra renal manifestations:Bilateral sensorineural hearing loss (never congenital)Ocular abnormalities - anterior lenticonus (pathognomonic), macular flecks and corneal erosions.Rarely - Leiomyomatosis of the esophagus, tracheobronchial tree, and female genitals and platelet abnormalities.DiagnosisA careful family history+a screening urinalysis of first-degree relatives+an audiogram+ophthalmologic examination.Likely in the patient with hematuria and at least two of the followingMacular flecks, recurrent corneal erosions, GBM thickening and thinning, and sensorineural deafness.Absence of epidermal basement membrane staining for the a5 chain of type IV collagen in male hemizygotes and discontinuous epidermal basement membrane staining in female heterozygotes is pathognomonic for X-linked AS.Treatment:Progressive renal dysfunction leading to end-stage renal disease.Risk factors for progression - gross hematuria during childhood, nephrotic syndrome and prominent GBM thickening.Table for Different Electrolyte Imbalance:Combination of metabolic alkalosis, hypokalemia (high urinary losses of potassium and chloride, despite a state of relative volume depletion with secondary hyperaldosteronism), a high urine chloride level, and normal blood pressure is characteristic of Bartter syndrome, Gitelman syndrome and current diuretic use.Bartter syndrome is usually associated with hypercalciuria, and often with nephrocalcinosis.Children with Gitelman syndrome have low urinary calcium losses but hypomagnesemia as a consequence of urinary magnesium losses.