Key words

Neonatal Bartter syndrome, Hypokalemic metabolic alkalosis.

INTRODUCTION

Bartter syndrome is an inherited renal tubular disorder characterized by hypokalemia, hypochloremic metabolic alkalosis, normal blood pressure with hyperreninemia and increased urinary loss of sodium, potassium and chloride. The neonatal form of Bartter syndrome is rare and clinically manifests with failure to thrive, polyuria and episodes of dehydration. We report two infants with neonatal Bartter syndrome, who had typical clinical features, but early diagnosis was not made. Both improved with administration of Indomethacin and potassium supplements.

CASE REPORT

CASE 1

A 15- month- old boy was referred with complaints of failure to thrive since birth. He was a term small for gestational age (birth weight 1.8 Kg) and was a product of non- consanguineous marriage. Maternal polyhydramnios was detected in the fifth month of pregnancy. There was no history of birth asphyxia. He was exclusively breastfed for the first three months of life after which cow milk was given and by 5th month of life, complementary feeds were introduced, which were poorly tolerated. He showed poor oral acceptance for solids yet would consume liquids in large amounts and pass urine frequently. He developed vomiting, around 2-3 times a day, non-bilious, non-projectile, being partially relieved by anti-emetics. The weight gain was poor (4.5 Kg at 12 months).

At age of 14 months, he developed fever with respiratory distress, needing hospital admission for 10 days and was treated with intravenous antibiotics. Metabolic alkalosis was detected and he was referred to this hospital. There was no history of child neglect or parental discordance. There was no history of loose stools, cyanotic spells, seizures, altered sensorium and focal neurological deficits.

Examination showed weight 4 Kgs (expected 11.21 Kgs), length 60 cm (expected 79.4 cm) and head circumference 42 cms (<3 rd centile). He had no dysmorphic features. The blood pressure was normal. Systemic examination was within normal limits and neurological examination did not disclose any localizing signs. Detailed laboratory evaluation showed hypochloremic metabolic alkalosis, hypokalemia, increased urinary losses of K+, Ca++ and raised aldosterone level(Table 1), confirming the diagnosis of Bartter syndrome. Ultrasound abdomen revealed bilateral medullary nephrocalcinosis. The child was managed with Indomethacin 2 mg/Kg, potassium supplementation and supportive treatment along with dietary advice. On discharge, there was clinical and biochemical improvement with serum potassium of 4.2 meq/l. On regular follow-up visit upto present age of 5 yrs , he has showed consistent gain in weight.

CASE 2

A 7 ½ month old baby boy, resident of Kabul, Afghanistan, presented with complaints of failure to thrive, cough and polyuria since 4 months. He was a product of 2nd degree consanguineous marriage born as a term appropriate for gestational age by vaginal delivery. There was maternal history of polyhydramnios. There was no history of birth asphyxia. Family history was not significant.

The child required frequent hospitalizations for persistent cough in Kabul & Pakistan. Investigations on blood had shown low Na+, K+, Cl-, Mg+ and a high HCO3-, Aldosterone, PgE, Renin along with metabolic alkalosis. Ultrasound abdomen showed hyperechogenic kidneys. The chest Xray was normal. Nuclear scan was positive for gastroesophageal reflux. A provisional diagnosis of Bartter syndrome was made and he was referred to this hospital.

On examination his weight was 4.86 kg (expected 8.64 kg ), length 62.5 cm (expected 69.5 cm ) and head circumference 38 cms (<3rd centile).He had mild pallor and normal BP. Systemic examination was within normal limits. Laboratory investigations(Table) showed metabolic alkalosis and increased urinary excretion of K+ and Ca+. The Chest X Ray and ultrasound abdomen were normal.

Child was managed with Indomethacin, potassium supplementation and supportive treatment and discharged in stable condition. On follow-up he showed marked clinical and biochemical improvement.

DISCUSSION

The two patients we described had typical abnormalities of Bartter syndrome. Although, the typical features were present almost since birth, the diagnosis was delayed by several months. There was marked clinical improvement with initiation of Indomethacin and potassium supplements.

Bartter syndrome is an inherited renal tubulopathy which may manifest during the neonatal period, infancy or childhood(1). The sodium potassium 2 chloride co-transporter NKCC2 or the luminal Potassium channel ROMK causes neonatal Bartter syndrome, where tubular losses of sodium, potassium, chloride and water cause secondary hyperaldosteronism(3,1). Bhankar and Gajendragadkar have recently described a case report on Antenatal Bartter syndrome with sensorineural deafness.

Gittelman syndrome however is a phenotypically related channelopathy instead of being a variant of Bartter’s syndrome, affecting Sodium chloride co- transporter NCCT present in the distal convoluted tubule. Linkage analysis and mutational studies have revealed defects in the gene encoding Sodium chloride co- transporter NCCT(3). The neonatal variant is particularly uncommon.

Antenatal features include polyhydramnios and premature delivery(4). Amniotic fluid shows consistently elevated chloride levels. After birth, rapid weight loss may occur(5,6,7). Lethargy and poor feeding often develop(8). Special facial features like triangular face, prominent forehead, large eyes, strabismus, protruding ears, drooping mouth exist as also sensorineural deafness, convulsions and increased susceptibility to infections(4).

Metabolic alkalosis with hypokalaemia occurs in the first week of life. Urine has low specific gravity with very high sodium, chloride and calcium levels while potassium is normal(8). However, after 1–3 weeks, the level of potassium in the urine rises with relatively less level of sodium than in the first week of life. Prostaglandin levels are high, both in blood and in urine(8,9). Hyperprostaglandin E2 is a secondary phenomenon due to fluid and electrolyte loss, and is suppressed by appropriate fluid and electrolyte replacement over a period of time. Serum Renin and Aldosterone levels are also very high, and are important in establishing the diagnosis. Untreated infants fail to thrive, and may die in a few days as a result of dehydration, poor feeding or severe electrolyte disturbance. Mild mental retardation is linked to delay in diagnosis and treatment(8).

Therapeutic efforts should be directed to correct dehydration and electrolytic imbalance(10). The treatment of Bartter syndrome consists of supplementation of potassium (1 – 3 meq/kg/day) and after 6 – 12 weeks of life, administration of Indomethacin (2 – 3 mg/kg/day)(1,4). Ibuprofen (30 mg/kg/day) has similar effect, but Indomethacin has been more widely used. The treatment results in striking clinical improvement although serum potassium levels may not increase to above 3.5 meq/l. Potassium sparing diuretics and angiotensin converting enzyme inhibitors have also been used(1).

Prenatal diagnosis can be made by the high chloride content of the amniotic fluid and mutational analysis of genomic DNA extracted from cultured amniocytes(11).

Bartter syndrome and other renal tubulopathies should be considered in an infant with no obvious cause of failure to thrive and unexplained polyuria. Early investigation and treatment should begin to prevent long term side effects like growth failure, nephrocalcinosis and renal failure.

REFERENCES

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