- Bartter syndrome.

 Bartter syndrome

The pathogenesis:

Failure of chloride reabsorption in the thick ascending limb of the loop of Henlé,thus resembling the pharmacological effect of furosemide (frusemide)

Bartter syndrome has been associated with 5 distinct genetic defects in loop of Henle transporters:

CCD, cortisol collecting duct; DCT, descending convoluted tubule; PGE2, prostaglandin E2; TAL, thick ascending loop of Henle.

As a secondary response to salt wasting, there is activation of the renin–angiotensin–aldosterone pathway in an attempt to recover sodium chloride in the distal nephron.

This is achieved at the expense of increased potassium and hydrogen ion secretion, which largely explains the hypokalemic alkalosis.

Clinical picture:

Neonatal period:

ü  Such infants are usually born prematurely after a pregnancy complicated by polyhydramnios.

ü  In early life they may become so volume depleted as to experience secondary oliguric renal failure, during which time the hypokalemic alkalosis is masked.

ü  Severe episodes of recurrent dehydration,In this group, there is hypercalciuria and bone demineralization, which may be secondary to the increased production of prostaglandins PGE2 and PGI2, which are found in this and other forms of Bartter syndrome.

ü  Consanguinity suggests the presence of an autosomal recessive disorder.

Children present with

ü  failure to thrive,

ü  hypotonia,

ü  lethargy,

ü  Muscle cramps

ü  Muscle weakness.

ü  poor feeding,

ü  constipation.

ü  polydipsia and polyuria.

ü  normal to low blood pressure

Nephrocalcinosis is a serious and early complication (Type 1,2).

Investigations:

Serum chemistry reveals the classic biochemical abnormalities of a hypokalemic metabolic alkalosis.

·      Urine:

ü  Electrolytes (Na+, K+ and Cl– all are high)

ü  DD from vomiting by urine chloride which is high in barrters syndrome.

ü  Calcium may be high

· Plasma electrolytes:

ü  Sodium (variable),

ü  Hypocholermic

ü  Hypokalemic

ü  Low magnesium

ü  Normal calcium

· High plasma bicarbonate

· Renal function is typically normal.

· Renal ultrasonogram for nephrocalcinosis

· Genetic analysis.

· Kidneys demonstrate hyperplasia of the juxtaglomerular apparatus. Renal biopsy is rarely performed to diagnose this condition.

Management

·         Potassium (Goals are to maintain serum potassium levels >3.5mmol/L),

·         sodium and chloride replacement.

·         Prostaglandin inhibitors such as indometacin which reduces renal salt, water and potassium loss. Th e dose of indomethacin is 0.5–1 mg/kg/day, divided into 4 doses, with stepwise increase to a maximum of 2–4 mg/kg/day.ACEIs such as captopril may give additional control.

·         Bartter syndrome presenting in older children may run a relatively mild course without hypercalciuria or nephrocalcinosis. Simple potassium supplementation may be all that is required.

·         In a minority of patients,chronic hypokalemia, nephrocalcinosis, and chronic indomethacin therapy can lead to chronic interstitial nephritis and chronic renal failure.

References:-

1. Moin A. Saleem, Jane Tizard, Jan Dudley, Carol Inward, Richard Coward, Mary McGraw, Disorders of the urinary system, Forfar & Arneil’s TEXTBOOK of PEDIATRICS, Seventh Edition
2. Illustrated Textbook of Pediatrics SECOND EDITION CH16
3. Rajasree Sreedharan and Ellis D. Avner, Bartter and Gitelman Syndromes and Other Inherited Tubular Transport Abnormalities, Chapter 531, NELSON TEXTBOOK OF PEDIATRICS, TWENTIETH EDITION 2016
4. Oxford Handbook of Paediatrics 2^nd ed  CH11 nephrology