Hypokalemic Hypochloremic Metabolic Alkalosis Research Articles

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Questions.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Questions.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Answers.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Answers.

The utility of next generation sequencing in the correct diagnosis of congenital hypochloremic hypokalemic metabolic alkalosis

Persistent hypokalemic hypochloremic metabolic alkalosis represents a heterogeneous group of genetic disorders of which the most common is Bartter syndrome (BS). BS is an inherited renal tubulopathy caused by defective salt reabsorption in the thick ascending loop of Henle, which results in persistent hypokalemic hypochloremic metabolic alkalosis. Here we report a 10-year-old girl of a consanguineous family. She presented prenatally with severe polyhydramnios and distended bowel loops. Thereafter, she displayed failure to thrive and had recurrent admissions due to dehydration episodes associated with diarrhea, and characterized by hypokalemia, hypochloremia and metabolic alkalosis. BS was considered her working diagnosis for several years despite negative genetic analysis of the known genes associated with BS. Whole exome sequencing identified a novel homozygous c.1652delT deleterious frameshift mutation in the SLC26A3 gene, which confirmed the diagnosis of congenital chloride diarrhea (CCD), a rare autosomal recessive disease that mimics biochemically BS. A review of twelve additional reported cases of CCD that were initially misdiagnosed as BS, emphasizes CCD in the differential diagnosis of BS, and highlights the clinical discrepancies between these two entities. Taken together, our report further emphasizes the typical clinical features of CCD, and the importance of next generation sequencing in the diagnosis of syndromes with genetic heterogeneity. We suggest including SLC26A3 in the extended BS targeted gene panels.

Growth hormone deficiency in children with antenatal Bartter syndrome.

Background Bartter syndrome is a group of rare autosomal-recessive renal disorders characterized by hypokalemic hypochloremic metabolic alkalosis associated with severe growth failure; the exact causes for growth retardation are unclear. GH deficiency (GHD) has been reported in a few cases of Bartter syndrome. The aim of our study was to determine the prevalence of GHD in children with antenatal Bartter syndrome and to assess their response to GH therapy. Methods Ten patients aged 1.5-14.5 years and diagnosed with antenatal Bartter syndrome were enrolled. Seven children with short stature underwent GH stimulation tests. Results Common presenting symptoms were failure to thrive and polyuria. The mean patient height at study entry was -2.7 standard deviation (SD) (range 0.89 to -5.95) and mean weight (SD) was -1.7 (range 1.89 to -4.11). A decline in height and weight (SD) was observed over the years. GHD was diagnosed in four children and GH therapy was started in all of them. Two patients responded very well and gained >1 SD in height, one patient stopped therapy due to non-adherence and one had a poor response. Conclusions In addition to other important causes for poor growth in antenatal Bartter syndrome, our findings suggest that GHD should also be considered as a cause of growth retardation and therefore, clinical assessment of the GH axis is recommended. GH therapy has a role in the treatment of growth failure in some individuals with Bartter syndrome.

Antenatal bartter syndrome caused by a novel homozygous mutation in SLC12A1 Gene

Antenatal Bartter syndrome (BS) is an autosomal recessive hereditary renal tubular disorder caused by mutation in the solute carrier family 12 member 1 (SLC12A1) gene on chromosome 15q21.1. This syndrome is characterized by polyuria, hyponatremia, hypokalemic hypochloremic metabolic alkalosis, and hypercalciuria associated with increased urinary loss of electrolytes. Herein, we report a very low-birth-weight premature newborn with antenatal BS caused by a novel homozygous mutation in the SLC12A1 gene, c.596G>A (p.R199H).

Gastric-Outlet Obstruction

Clinical Image: An 80-year-old lady presented after “passing out” on rising from her bed. This was preceded by 4 weeks of diffuse, dull, intermittent, non-radiating abdominal pain, associated with bloating, which was more to solids than liquids and relieved by vomiting. She noted early satiety, a 15 lbs weight loss (last 3 months) and constipation. Examination revealed a malnourished woman with temporal and supraclavicular wasting. Her abdomen was distended, tender, with a “succussion splash” 9 hours after her last meal. Lab results were consistent with hypokalemic hypochloremic metabolic alkalosis and prerenal azotemia. Abdominal radiograph showed inferior displacement of Transverse Colon (Figure 1A). Computed Tomography (CT) showed a distended stomach, pyloric inflammation (Figure 1B) and partial gastric outlet obstruction (GOO) (Figure 1C). Subsequent EGD showed pyloric stenosis with partially obstructing duodenal bulb ulceration. Biopsy was negative for H. pylori infection, scar tissue or malignancy. She was treated with intermittent NG tube suction and intravenous proton pump inhibitors (PPI’s). Her diet was progressively advanced. She was discharged home on oral PPI’s and was symptom free at 4-week follow-up.

Evaluation of Hypertrophic Pyloric Stenosis by Pediatric Emergency Physician Sonography

The objective was to evaluate the accuracy of pediatric emergency physician (EP) sonography for infants with suspected hypertrophic pyloric stenosis (HPS). This was a prospective observational pilot study in an urban academic pediatric emergency department (PED). Patients were selected if the treating physician ordered an ultrasound (US) in the department of radiology for the evaluation of suspected HPS. Sixty-seven patients were enrolled from August 2009 through April 2012. When identifying the pylorus, pediatric EPs correctly identified all 10 positive cases, with a sensitivity of 100% (95% confidence interval [CI] = 62% to 100%) and specificity of 100% (95% CI = 92% to 100%). There was no statistical difference between the measurements obtained by pediatric EPs and radiology staff for pyloric muscle width or length (p = 0.5 and p = 0.79, respectively). Trained pediatric EPs can accurately assess the pylorus with US in the evaluation of HPS with good specificity.

Congenital chloride diarrhea: late presentation

Correspondence: Laila Al Bishi Consultant General Pediatrician, Pediatric Department North West Armed Forces Hospital, Tabuk, Kingdom of saudi Arabia Tel +966 44411088 ext 85363 Fax +966 44411056 email toonisi@gmail.com Abstract: We report the case of a male infant who presented with diarrhea at 6 months of age. He was failing to thrive, and biochemical investigation revealed hypokalemic hypochloremic metabolic alkalosis. Diagnosis of congenital chloride diarrhea was suspected and confirmed by the stool chloride result. He was started on high-dose sodium chloride and potassium chloride to control the electrolyte imbalance. The disease was difficult to control for a year after diagnosis. Late presentation is associated with severe chronic electrolyte disturbances and high-dose replacement therapy.

Vomiting in a 22-day-old firstborn male

A 22-day-old healthy appearing male infant presented with persistent vomiting after feeding with onset shortly after birth. This is the father’s second child and the mother’s first. Switching formulas had been unsuccessful. Abdominal X-ray (AXR) revealed a dilated air-filled stomach with a nonspecific bowel gas pattern (Fig. 1). Ultrasound (US) demonstrated a thick and elongated pylorus, confirming the diagnosis (Figs. 2 and ​and33). Fig. 1 AXR showing a dilated and air-filled stomach Fig. 2 US showing an elongated and thickened pylorus Fig. 3 US view from a slightly different angle confirms the measurements Pyloric stenosis is an important cause of gastric outlet obstruction and vomiting in infants. Peak incidence occurs between 2 and 5 weeks of age with an incidence of 1–8 per 1,000 live births. Male infants are predominantly affected 4:1 over female infants [1]. There is a familial component, with sons of affected fathers carrying a 5% risk of pyloric stenosis [2]. The cardinal feature of this disorder is projectile, nonbilious vomiting that occurs anywhere from the end of feeding up to 30 min after. Afterwards the infant exhibits a desire to feed more. Persistent emesis results in hypokalemic hypochloremic metabolic alkalosis with dehydration. Palpation of an olive-shaped, muscular, mobile, and nontender mass in the left upper quadrant is pathognomonic of this condition. During feeding, gastric peristaltic waves can sometimes be observed from left to right upper abdominal quadrants. Radiographic signs of pyloric stenosis include gastric distension with air, a maximal gastric diameter of 7 cm or greater, and thick walled gastric antrum [3]. Abdominal US confirms the diagnosis by illustrating the increased length and thickness of the pyloric muscle. Before surgical treatment, correction of dehydration and serum electrolytes is necessary. Definitive therapy is pyloromyotomy with an excellent outcome [4].

A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. A 10-year-old boy had severe growth retardation (height standard deviation score -8.15). He had a thin, triangular face, prominent ears and forehead, and big eyes. Megacystis, bilateral hydroureteronephrosis, and residual urine were detected in ultrasonography, but there was no vesicoureteral reflux. Lumbosacral magnetic resonance (MR) showed posterior disc bulging at L4-5. Serum sodium and chloride levels were normal, but mild hypokalemia was overlooked initially. During follow-up, hypokalemic hypochloremic metabolic alkalosis developed, with high urinary chloride and potassium excretion (52 and 43 mEq/L, respectively). The patient, with renal salt loss, was thought to have classic Bartter syndrome due to absence of nephrocalcinosis, presence of persistent hypercalciuria and sensorineural deafness, and presence of relatively mild clinical and laboratory findings, except polyuria initially. The child was treated with indomethacin, spironolactone, and oral potassium in addition to growth hormone (GH). During treatment, he had considerable increase in weight and height compared with the period of GH therapy only. We present this case because, although growth retardation is a major feature of Bartter syndrome, associated GH deficiency is rarely reported in the literature. Diagnosis of Bartter syndrome was made later, as our patient was followed for megacystis and megaureter secondary to the neurogenic bladder and GH deficiency initially; and proteinuria associated with focal segmental glomerulosclerosis responded to treatment for Bartter syndrome.

Linkage of Infantile Bartter Syndrome with Sensorineural Deafness to Chromosome 1p

Bartter syndrome (BS) is a family of disorders manifested by hypokalemic hypochloremic metabolic alkalosis with normotensive hyperreninemic hyperaldosteronism. We evaluated a unique, inbred Bedouin kindred in which sensorineural deafness (SND) cosegregates with an infantile variant of the BS phenotype. Using a DNA-pooling strategy, we screened the human genome and successfully demonstrated linkage of this unique syndrome to chromosome 1p31. The genes for two kidney-specific chloride channels and a sodium/hydrogen antiporter, located near this region, were excluded as candidate genes. Although the search for the disease-causing gene in this family continues, this linkage further demonstrates the genetic heterogeneity of BS. In addition, the cosegregation of these phenotypes allows us to postulate that a single genetic alteration may be responsible for the SND and the BS phenotype. The identification and characterization of this gene would lead to a better understanding of the normal physiology of the kidney and the inner ear.

Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS.

Congenital Chloride Diarrhea

Congenital chloride diarrhea (CCD) is a common metabolic disorder in Saudi children with an incidence of 1 in 5,500. The present retrospective study from Saudi Arabia, over 7.5 years, presents the clinical, biochemical, and treatment details in 10 children with CCD. The perinatal characteristics of maternal polyhydramnios, prematurity, abdominal distention, and diarrhea were seen in 100% and hyperbilirubinemia in 90% of patients. Hypokalemic hypochloremic metabolic alkalosis was a feature in 50% of the children and acidosis in both neonates. Fecal chloride greater than 100 mmol/L in 100% and fecal chloride greater than the sum of fecal sodium and potassium were found in 55% of patients. The mean age at the time of diagnosis was 10 months and the mean duration of follow-up for the group was 38 months (range 2-89 months). Eight of the nine patients treated with continuous oral electrolyte solution demonstrated "catch-up" physical growth. Mental subnormality, growth retardation, and renal impairment were seen in one patient who failed to comply with the treatment. Cerebral palsy in another child was due to neonatal intraventricular hemorrhage.