Case Report iMedPub Journals Journal of Rare Disorders: Diagnosis & Therapy 2019 www.imedpub.com ISSN 2380-7245 Vol.5 No.2:4 DOI: 10.36648/2380-7245.5.2.196 Congenital Chloride Diarrhea in a Bartter Maria Helena Vaisbich*, Juliana Caires de Oliveira Syndrome Misdiagnosed Brazilian Patient Achili Ferreira, Ana Carola Hebbia Lobo Messa and Abstract Fernando Kok The differential diagnosis in children with hypokalemic hypochloremic alkalosis Department of Pediatric Nephrology, include a group of an inherited tubulopathies, such as Bartter Syndrome (BS) Instituto da Criança, University of São Paulo, and Gitelman Syndrome (GS). However, some of the clinically diagnosed São Paulo, Brasil patients present no pathogenic mutation in BS/GS known genes. Therefore, one can conclude that a similar clinical picture may be caused by PseudoBartter Syndrome (PBS) conditions. PBS include acquired renal problems (ex.: use of diuretics) as well as genetic or acquired extrarenal problems such as cystic *Corresponding author: fibrosis or cyclic vomiting, respectively. The accurate diagnosis of BS/GS needs Maria Helena Vaisbich a rational investigation. First step is to rule out PBS and confirm the primary renal tubular defect. However, it is not easy in some situations. In this sense, Department of Pediatric Nephrology, we reported a patient that was referred to our service with the diagnosis Instituto da Criança, University of São Paulo, of BS, but presented no mutation in BS/GS known genes. The whole-exome São Paulo, Brasil. sequencing detected a SCL26A3 likely pathogenic mutation leading to the final diagnosis of Congenital Chloride Diarrhea (CCD). Reviewing the records, the [email protected] authors noticed that liquid stools were mistaken for urine. In addition, urinary and fecal samples were collected at an inappropriate time. The fecal sample taken during dehydration led to a low fecal chloride level and urine taken soon Tel: +55-11-99940-3433 after sodium and potassium chloride infusion led to a high urinary chloride fractional excretion. Based on this data, BS was misdiagnosed. Our goal is to report the first Brazilian CCD patient initially misdiagnosed as BS and discuss Citation: Vaisbich MH, Ferreira JCDOA, the difficulties to achieve the correct diagnosis in clinical practice. Messa ACHL, Kok F (2019) Congenital Chloride Keywords: Alkalosis; Child; Bartter syndrome; Gitelman syndrome; Congenital Diarrhea in a Bartter Syndrome Misdiagnosed chloride diarrhea; Hypokalemia Brazilian Patient. J Rare Disord Diagn Ther. Vol.5 No.2:4 Abbreviations: BS: Bartter Syndrome; GS: Gitelman Syndrome; PBS: PseudoBartter Syndrome; CCD: Congenital Chloride Diarrhea; CFTR: Cystic Fibrosis Transmembrane Conductance Regulator Received: August 16, 2019; Accepted: November 11, 2019; Published: November 18, 2019 Introduction aldosterone in childhood include a group of an autosomal recessive salt-loss tubulopathies, such as Bartter Syndrome General pediatricians are frequently the first professionals to (BS) and Gitelman Syndrome (GS) [3]. However, variants in detect metabolic and electrolyte disturbances in childhood known BS/GS genes have not been identified in some patients and they should be aware of the differential diagnosis. In cases [4] suggesting other rare diseases may cause a PseudoBartter of persistent hypochloremic hypokalemic metabolic alkalosis, Syndrome (PBS). Table 1 summarizes the main differential acquired situations such as cyclic vomiting, chloride-intake diagnosis of this metabolic and electrolyte disturbance and deficiency, laxative abuse, diuretics use or nephrotoxic agents provides some details of the etiologies. The clinical diagnosis of have to be investigated [1]. However, the late diagnosis could be BS can be achieved with a rational investigation excluding PBS harmful to patients with some rare genetic diseases [2]. In this and confirming the primary renal tubular dysfunction. However, context, the differential diagnosis of persistent hypochloremic it is not easy in some situations. Congenital Chloride Diarrhea hypokalemic metabolic alkalosis with high serum renin and (CCD), a disease characterized by fecal chloride waste, can © Under License of Creative Commons Attribution 3.0 License | This article is available from: https://raredisorders.imedpub.com 1 Journal of Rare Disorders: Diagnosis & Therapy 2019 ISSN 2380-7245 Vol.5 No.2:4 2 Table 1 Differential diagnosis of persistent hypochloremic hypokalemic metabolic alkalosis in childhood. Genetic Diseases Summary of Epidemiological Disease/Inheritance Genetics and Special Clinical Manifestations Lab Findings Treatment Data Pathogenesis Renal Genetic Diseases Pathogenic loss of function mutations Polyhydramnios (fetal polyuria) in SLC12A1 (15q15-q21) ↑ plasmatic renin and aldosterone; hypercalciuria; and prematurity. Life-threatening encoding Na+-K+-Cl- ↑K+FE, ↑Na+FE, ↑Cl-FE; isothenuria/ electrolyte disturbances; early BS Type cotransporter (NKCC2), hyposthenuria. nephrocalcinosis. 1/AR unknown leading to Na+, K+ and Cl- urinary waste There is no specific treatment. pathogenic loss of Treatment is based on electrolytes function mutation in supplementation and prostaglandin KCNJ1(11q24), which Similar to BS type 1, but less severe Similar to BS type 1, but newborns can present inhibitors objecting to reduce BS Type encodes ROMK, leading hypokalemic alkalosis. transient hyperkalemic metabolic acidosis. polyuria. AARS inhibitors can be 2/AR unknown to Na+, K+, Cl- urinary employed in selective cases with losses close monitoring of renal function Pathogenic mutation in and blood pressure. BSND (1p31) encoding In addition to the metabolic and Spironolactone can also be used to barttin a subunit of CLC- electrolyte disturbances patients Similar to BS type 1 Antenatal BS Type increase K+ tubular reabsorption. unknown Kb, responsible for its present sensorineural deafness. BS 4a/AR activation Compound heterozygous mutation In addition to the metabolic and in CLCNKA/CLCNKB, electrolyte disturbances patients Similar to BS type 1 BS Type unknown leading to Na+, K+, and present sensorineural deafness. 4b/DR Cl- urinary waste Unknown, but was the most Classic manifestations: failure Electrolytes supplementation and common type in Pathogenic mutations in to thrive, polydipsia, polyuria, prostaglandin inhibitor, preferably BS/GS patients CLCNKB, encoding CLC- vomiting, episodes of fever and COX 2 selective one. Inhibitors of evaluated at Nephrocalcinosis is uncommon and, patients can Kb (1p36) and leading to hypotension about 6 – 12 months AARS can be employed monitoring the Instituto present hypomagnesemia and hypercalciuria. urinary losses of Na+, K+ of age. However, there is a great renal function and blood pressure. da Criança – Classic BS - BS type and Cl-. phenotype overlap among classic Spironolactone can be used to HCFMUSP, Brazil 3/AR and antenatal forms. increase K+ tubular reabsorption. (unpublished data) Pathogenic mutations in MAGED2 (Xp11.21), Early manifestation with severe which encodes polyhydramnios and prematurity; ↑ plasmatic aldosterone and renin; MAGED2 associated MAGE-D2 protein Unknown high mortality rate. Notably, the ↑ K+FE, ↑Na+FE, Electrolytes supplementation BS (transient BS) implicated in the Few cases survivors evolving with complete ↑Cl-FE BS type 5/ regulation of NKCC2 and reported clinical resolution. X-linked recessive NCC, leading to severe antenatal form of BS. This article is available from: https://raredisorders.imedpub.com Journal of Rare Disorders: Diagnosis & Therapy 2019 ISSN 2380-7245 Vol.5 No.2:4 Genetic Diseases Pathogenic gain of function variants in CASR (3q13.3-q21.1), which encodes the Thiazides diuretics can be used CaSR, a calcium sensible Generally asymptomatic to decrease hypercalciuria and receptor. hypocalcemia, but there are cases Hypocalcemia and hypercalciuria (↑Ca++FE); ↑ also increase calcemia. PTH Therefore, even when present with seizures or tetany, urinary Na+, K+ and Cl-. ↑renin and aldosterone. supplementation can also be an the serum calcium is with hypercalciuria, have low- ↓ PTH. option. low, the hypercalciuria normal serum PTH concentrations 10% of the patients present nephrocalcinosis; 35% Calcium supplementation Hypocalcemia unknown persists. The K+ urinary and have often been diagnosed basal ganglia calcification and vitamin D. Na+, K+ and Cl- autosomal dominant wasting can be due to with hypoparathyroidism. supplementations are necessary. with BS /AD ROMK direct inhibition or due to electrogenic potential differential gradient. Pathogenic loss of function variants in Symptoms are uncommon in SLC12A3, which encodes ↑ plasmatic aldosterone and renin; Sodium, chloride and potassium children < 6 years old; more often NCC, leading to excessive ↑ K+FE, ↑Na+FE, rich diet and electrolytes occur in adolescents and young urinary loss of Na+, Cl-, K+ ↑Cl-FE supplementation Gitelman Syndrome/ Prevalence adults; hypotension is often. and Mg++, hypocalciuria AR 1-9:100.000 and hypomagnesemia Pathogenic gain of function variants in SCNN1B and SCNN1G, hypertension in children, young plasmatic aldosterone and renin; Liddle Syndrome encoding ENaC, leading adults and adolescents, specially ↑ K+FE; ENaC inhibitors as amiloride and (pseudo Prevalence to excessive sodium in familial cases; failure to thrive in ↓ Na+FE; triamtere hyperaldosteronism)/ <1: 1.000.000 reabsorption, and infants AD excessive urinary loss of K+ and H+. Dent type 1: Pathogenic mutations in CLCN5 (Xp11.22), which encodes the electrogenic The disease manifests