A Case of Secondary FSGS due to Chronic Chloride Diarrhea

Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease that is difficult to diagnose. CLD requires early treatment to correct electrolyte imbalance and alkalosis and to prevent severe dehydration. Renal injury is clearly associated with defective electrolyte balance induced by CLD, particularly during the first months or years of life. A 7-year-old boy was diagnosed with CLD following detection of a homozygous mutation (c.2063-1G>T) in SLC26A3 at 6 months of age. During treatment with electrolyte supplements, mild proteinuria was detected at 8 months of age, and is still present. Renal biopsy showed the presence of focal renal dysplasia, with metaplastic cartilage and mononuclear cell infiltration, calcification, and fibrosis in the interstitium. Up to two-thirds of the glomeruli exhibited global obsolescence, mostly aggregated in the dysplastic area. In nondysplastic areas, the glomeruli were markedly increased in size and severely hypercellular, with increased mesangial matrix, and displayed segmental sclerosis. The marked glomerular hypertrophy with focal segmental glomerulosclerosis suggested a compensatory reaction to the severe nephron loss or glomerular obsolescence associated with renal dysplasia, with superimposed by CLD aggravating the tubulointerstitial damage.

Oral Proton Pump Inhibitor for Treatment of Congenital Chloride Diarrhea

Congenital chloride diarrhea (CCD) is a rare autosomal recessive disease, which is characterized by electrolyte absorption defect due to impaired function of the Cl-/HCO3 - exchanger in the ileum and the colon. Its main features are profuse watery diarrhea, high fecal chloride concentration, and failure to thrive. Profuse watery diarrhea characterized by a high concentration of chloride in stools results in hypochloremia, hyponatremia, and dehydration with metabolic alkalosis. Early detection and therapeutic intervention can prevent life-threatening symptoms of CCD and growth failure. Recently, several therapies, such as proton pump inhibitors and butyrate, have been suggested for amelioration of diarrhea. Here, we report a case of CCD in a preterm male infant who was successfully treated with an oral proton pump inhibitor.

Clinical features and SLC26A3 genetic mutation analysis of a kindred with congenital chloride diarrhea / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and mutation of SLC26A3 gene of a patient with congenital chloride diarrhea in order to deepen the understanding of the disease.Methods The clinical data of the patient who was admitted in Affiliated Hospital of Capital Pediatric Institute in June 2014 were collected.Venous blood of the proband and his parents (2 mL for each) had been extracted for genomic DNA isolation.The 21 exons of SLC26A3 gene were amplified with polymerase chain reaction and screened for mutations by sequencing.Results The main clinical features of the patient included polyhydramnios,preterm,normal birth weight,watery diarrhea,low weight and severe electrolyte disturbances with hypochloremia,hypokalemia,hyponatremia and metabolic alkalosis.Renin angiotensin and aldosterone were high.His urine chloride concentration was low and fecal chloride concentration was high (＞ 90mmol/L).After oral salt substitution therapy with KCl and NaCl [3 mmol/(kg · d),4 mmol/(kg · d)],the electrolyte was better,alkalosis was alleviated,and growth and development were improved.The gene analysis revealed that the patient carried nt1631T ＞ A homozygous mutation on exon 15 which lead to Ile544Asn mutation in the predicted SLC26A3 transmembrane protein sequence,which was considered to be responsible for the functional abnormality of the Cl-/HCO3-protein.His parents were carriers of SLC26A3 gene and their clinical phenotype was normal.Conclusions Congenital chloride diarrhea is a rare autosomal recessive disorder and easily misdiagnosed.The patient of early postnatal diarrhea with persistent hypochloremia,hypokalemia,hyponatremia and metabolic alkalosis should be thought about this disease.Genetic analysis can help make the diagnosis.The prognosis is good if a patient has an early diagnosis and appropriate management.

Congenital chloride diarrhea：one case report / 临床儿科杂志

ObjectiveTo discuss the clinical diagnosis, treatment and genetic diagnosis of congenital chloride diarrhea (CCD), a rare autosomal recessive disease.Methods One month old boy with persistent diarrhea, hypochloremia, hyponatremia, hypokalemia and metabolic alkalosis, his stool electrolyte testing, clinical treatment and follow-up, as well as his and his parents’ SLC26A3 gene mutation analysis were retrospectively analyzed.Results The fecal electrolyte testing showed that the levels of Cl- and K+ were increased and the level of Cl- was much higher than the sum of Na+ and K+. After replacement therapy with NaCl and KCl, the blood electrolyte recovered to normal. Follow-up 4 years, the boy had a normal growth and development. Mutation analysis onSLC26A3 gene showed there was a homozygous mutation of 239G>A and both his father and mother carried the same heterozygous mutation. This mutation was ifrst discovered in China.Conclusions The sequencing analysis ofSLC26A3 mutation may help to diagnosis CCD.

Reporte de segundo caso en Cuba de clorhidrorrea congénita / Report of a second congenital chloride diarrhea case in Cuba

La clorhidrorrea congénita es un raro desorden autosómico recesivo, causado por un defecto en el intercambio de cloruro/bicarbonato en el íleon y colon. En este trabajo se reporta el caso de un niño de 1 año de edad con características patognomónicas de esta condición, consistentes en antecedentes prenatales de polihidramnios, diarreas acuosas desde el nacimiento, poca ganancia de peso, alcalosis metabólica y deshidratación. El diagnóstico fue confirmado por el elevado contenido de cloruro en heces, y es el segundo caso reportado en la literatura cubana.

Congenital chloride diarrhea is a rare autosomal recessive disorder caused by a defective exchange of chloride and bicarbonate in the ileum and the colon. This article reported the case of one-year old child with pathognomonic characteristics of this disease including prenatal history of polyhydramnios, watery diarrheas since birth, low weight gain, metabolic alkalosis and dehydration. The diagnosis was confirmed on the basis of the high contents of chloride in stools. He is the second case of this disease reported in the Cuban literature.

Congenital Chloride Diarrhea in Dizygotic Twins / 대한소아소화기영양학회지

Congenital chloride diarrhea (CLD) is a rare inherited autosomal recessive disorder. Mutations of the solute carrier family 26 member 3 gene cause profuse, chloride ion rich diarrhea, which results in hypochloremia, hyponatremia and metabolic alkalosis with dehydration. If a fetal ultrasound shows bowel dilatation suggestive of bowel obstruction, or if a neonate shows persistent diarrhea and metabolic alkalosis, CLD should be considered in the differential diagnosis. The severity of CLD varies, but early detection and early therapy can prevent complications including growth failure. We report a case of dizygotic twins affected by CLD who had been born to non-consanguineous parents. Both of them showed growth failure, but one of the twins experienced worse clinical course. He showed developmental delay, along with dehydration and severe electrolyte imbalance. He was diagnosed with CLD first at 6-month age, and then the other one was also diagnosed with CLD.

Identification of SLC26A3 Mutations in a Korean Patient with Congenital Chloride Diarrhea

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder with the hallmark of persistent watery Cl(-)-rich diarrhea from birth. Mutations in the solute carrier family 26, member 3 (SLC26A3) gene, which encodes a coupled Cl-/HCO3- exchanger in the ileum and colon, are known to cause CLD. Although there are a few reports of CLD patients in Korea, none of these had been confirmed by genetic analysis. Here, we describe the case of a Korean infant with clinical features of CLD. Using direct sequencing analysis, we identified 2 sequence variants: a missense variant of unknown significance (c.525G>C; p.Arg175 Ser) and a splicing mutation (c.2063-1G>T) in the SLC26A3 gene; these had been inherited from the father and mother, respectively. Whilst CLD is rare, its main symptom, diarrhea, is very common in infants. Hence, the diagnosis of CLD can prove difficult. Mutational analysis of the SLC26A3 gene should be considered as a viable method to confirm a diagnosis of CLD in Korean infants with persistent diarrhea.

Clorhidrorrea congénita / Congenital chloride diarrhea

Congenital chloride diarrhea (CCD) is a rare hereditary disease, with a prenatal onset, secondary to a deficit in the intestinal chloride transport. In the present study, we describe the clinical characteristics of three patients with congenital watery diarrhea, two of them females, aged between 9 and 14 months at the first visit. All patients presented perinatal antecedents of polyhydramnios and prematurity, watery stools since birth and growth failure. Metabolic alkalosis, hypokalemia and hypochloremia were found. Stool ionogram with elevated doses of chloride, exceeding both sodium and potassium, confirmed the diagnosis of CCD. Substitute treatment with sodium and potassium chloride was started with good results. CCD should be considered as a differential diagnosis to congenital watery diarrhea, since early diagnosis and appropriate treatment are mandatory for the normal development of the child, avoiding severe complications such as neurological sequelae and even death.

La clorhidrorrea congénita (CHC) es una enfermedad hereditaria rara, de comienzo prenatal secundaria aun defecto en el transporte intestinal de cloro. En este trabajo describimos las características clínicas de tres pacientes con diarrea acuosa congénita, dos desexo femenino, con edades comprendidas entre 9 y 14meses al momento de la consulta. Todos presentaban antecedentes perinatales de polihidramnios y prematurez,deposiciones líquidas desde el nacimiento y mal progreso ponderal. Se comprobó alcalosis metabólica,hipokalemia e hipocloremia. El ionograma en materia fecal, con dosajes de cloro elevado que superaban la sumade sodio y potasio, permitió confirmar el diagnóstico de CHC. Se instituyó tratamiento sustitutivo con cloruro de sodio y de potasio, con evolución favorable. Es de suma importancia tener en cuenta la CHC dentro de los diagnósticos diferenciales de diarrea acuosa congénita, ya que el diagnóstico precoz y el tratamiento adecuado permiten un desarrollo normal, evitandocomplicaciones graves, como secuelas neurológicas e incluso la muerte.

A Case of Congenital Chloride Diarrhea in Premature Infant

Congenital chloride diarrhea is a serious autosomal recessive disease, and defect of intestinal electrolyte absorption that involves, specifically, Cl-/HCO3- exchange in the distal part of the ileum and colon. The clinical feature is dominated by profuse, watery diarrhea containing high concentrations of chloride(> 90 mmol/L) and sodium. The chloride loss results in severe dehydration with a hypochloremic alkalosis. The molecular pathology involves an epithelial Cl - /HCO3 - exchanger protein. Mucosal ion transport is affected to differing degrees and the severity of the disease may thus vary. Recently, a gene defect on chromosome 7 has been identified. However, there was a deficit in replacement of fluid and electrolyte, abdominal distension remained and the character of stools was watery. We report a case of congenital chloride diarrhea in a premature female who presented with watery diarrhea containing high concentrations of chloride and abdominal distension.