Síndrome nefrótico congénito debutando con enfermedad de cambios mínimos / Congenital nephrotic syndrome debuting with disease of minimal changes

Resumen El síndrome nefrótico es la glomerulopatía primaria más frecuente en pediatría; es una patología que se caracteriza por la presencia de proteinuria, hipoalbuminemia, edema e hipercolesterolemia. Se habla de un neonato con antecedentes de prematuridad y hospitalización al nacer, posterior a múltiples infecciones recurrentes con evolución tórpida durante estancia hospitalaria y edema generalizado, de quien se sospecha tener síndrome nefrótico congénito, apoyándose en resultados paraclínicos positivos y una biopsia renal que reporte enfermedad de cambios mínimos. El síndrome nefrótico congénito es una entidad poco frecuente; sin embargo, presenta alta morbimortalidad, así como diversas formas de presentación clínica e histológica, y su manejo suele ser difícil dada la baja respuesta a corticoides. La presencia del síndrome nefrótico congénito es inusual, no obstante, presenta alta mortalidad y deja muchas secuelas, siendo la enfermedad renal crónica la más temida. Así que resulta importante sospechar en recién nacidos con infecciones recurrentes asociadas a presencia de edema generalizado para iniciar un manejo precoz que pueda ayudar a evitar consecuencias y mejorar la calidad de vida del paciente y su familia.

Abstract Nephrotic syndrome is the most common primary glomerulopathy in pediatrics; it is a pathology characterized by the presence of proteinuria, hypoalbuminemia, edema, and hypercholesterolemia. There is talk of a neonate with a history of prematurity and hospitalization at birth, after multiple infections recurrent with torpid evolution during hospital stay and edema generalized, suspected of having congenital nephrotic syndrome, relying on positive paraclinical results and a renal biopsy that reports minimal change disease. Congenital nephrotic syndrome is a rare entity; However, presents high morbidity and mortality, as well as various forms of clinical and histological, and its management is usually difficult given the low response to corticosteroids. The presence of congenital nephrotic syndrome is unusual; however, it presents high mortality and leaves many sequelae, with chronic kidney disease being the most feared. So, it is important to suspect in newborns with infections recurrent associated with the presence of generalized edema to initiate management early that can help prevent consequences and improve the quality of life of the patient and his family. .

Síndrome nefrótico congénito. Reporte de caso y revisión del enfoque diagnóstico / Congenital nephrotic syndrome. Case report and review of its diagnostic work up

Resumen El síndrome nefrótico se define como la unión de proteinuria masiva, hipoalbuminemia e hiperlipidemia, que pueden asociarse a edemas e hipercoagulabilidad. Se origina de una anormalidad de la barrera de filtración glomerular con una fuga masiva de proteína y los efectos secundarios consecuentes. En sus formas primarias, ocurre con una incidencia de 1-3 por cada 100.000 niños menores de 16 años. La forma congénita es una variante poco frecuente del síndrome nefrótico, la cual se presenta en el nacimiento o dentro de los tres primeros meses de vida, y suele ser resistente a la corticoterapia. Se debe evaluar primero la existencia de infecciones congénitas y luego buscar las enfermedades monogénicas más comunes, finalmente se puede recurrir a la secuenciación de nueva generación para buscar mutaciones en los demás genes candidatos. Se presenta el caso de una niña con síndrome nefrótico congénito de difícil control, enfatizando en el proceso diagnóstico y el manejo de soporte. Se resalta la importancia de la asesoría genética a la familia en todos los casos.

Abstract A nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminemia and hyperlipidemia, which may be associated with edema and hypercoagulability. It originates from an abnormality of the glomerular filtration barrier with a massive protein leak and the consequent side effects. In its primary forms, it occurs with an incidence of 1 - 3 per 100,000 children under 16 years of age. The congenital form is a rare variant of the nephrotic syndrome, which occurs at birth or within the first three months of life and is usually resistant to corticosteroid therapy. Congenital infections and most common related monogenic diseases should be tested. Finally, new generation sequencing must be used to search for mutations in other candidate genes. We present the case of a girl with congenital nephrotic syndrome difficult to control, emphasizing the diagnostic process and support management. The importance of genetic counseling to the family in all cases is highlighted.

Prenatal diagnosis of a fetus affected with Finnish type congenital nephrotic syndrome / 中华医学遗传学杂志

Objective@#To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF).@*Methods@#Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing.@*Results@#The fetus was found to carry compound heterozygous variants c. 1440+ 1G>A and c. 925G>T of the NPHS1 gene, which were respectively inherited from its mother and father.@*Conclusion@#Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.

Congenital nephrotic syndrome with neonatal polycythemia: a case report / 临床儿科杂志

Objectives To investigate the relationship between congenital nephrotic syndrome (CNS) and neonatal polycythemia, and clinical diagnosis and treatment. Methods The clinical manifestations, diagnosis, and treatment of a case of CNS with neonatal polycythemia were retrospective analyzed, and the related literature were reviewed. Results A male infant had abdominal distention after his birth, followed by feeding intolerance and poor response. On the third day of birth, he was diagnosed of neonatal polycythemia according to the levels of hemoglobin (249 g/L) and hematocrit (0.714 L/L). And after a partial exchange transfusion, the symptoms were improved. On the sixth day of birth, the infant had edema, urinary protein +++, serum albumin at 12.7 g/L and blood cholesterol at 8.84 mmol/L, and was clinical diagnosed of CNS. Oral hormone therapy was ineffective and he died 32 days after birth. Conclusions CNS combined with neonatal erythrocytosis is rare in clinic. The co-existing of the two is more likely to induce thromboembolism and organ dysfunction, and the clinical prognosis is poor.

The gene mutation in one neonate with Finnish type congenital nephrotic syndrome / 临床儿科杂志

Objective To investigate the NPHS1 gene mutations in Finnish type congenital nephrotic syndrome (CNF). Methods Clinical data of one neonate with CNF and the results of NPHS1 gene detection in the neonate and his parents were retrospectively analyzed. Results The male neonate who was born at gestational age of 34 weeks presented with breathing difficulties after birth, and then glycosuria, proteinuria, and hematuria at 3 days of age. The CNF was clinically diagnosed. The neonate carried two heterozygous mutations in NPHS1 gene, c.1699?>?C, p.(Cys567Arg) and c.3523_3524de1TT, p.(Leu1175Valfs). His father carried the heterozygous mutations of c.1699?>?C, p.(Cys567Arg). His mother carried the heterozygous mutations of c.3523_3524de1TT, p.(Leu1175Valfs). Conclusions The NHPSI gene mutation of c.1699?>?C, p.(Cys567Arg) and c.3523_3524de1TT, p.(Leu1175Valfs) may cause CNF. The mutation of c.1699?>?C, P. (Cys567Arg) has not been reported at home and abroad.

Síndromes nefróticos congénitos y hereditarios / Congenital and heritable nephrotic syndromes

En los últimos años se han identificado muchos síndromes nefróticos familiares y esporádicos que no responden a los tratamientos habituales (esteroides e inmunosupresores), evolucionan con relativa rapidez a la insuficiencia renal crónica y se producen por mutaciones genéticas. La mayoría de los síndromes nefróticos que se trasmiten genéticamente y que pueden ser congénitos, presentarse en el primer año de la vida, o en el niño mayor, son atribuidos a mutaciones en los genes NPHS1, NPHS2, WT1 y LAMB2. Otros síndromes nefróticos producidos por mutaciones genéticas pueden no manifestarse hasta la adultez. El objetivo fundamental de esta revisión fue llamar la atención sobre los síndromes nefróticos producidos por mutaciones genéticas en los que no sólo no se obtienen resultados con los tratamientos inmunosupresores, si no en los que dichos tratamientos pueden ser perjudiciales para el paciente

In past years many familial and sporadic nephrotic syndromes refractory to usual treatments (steroids and immunosuppressives), evolve quickly to a chronic renal failure produced by genetic mutations. Most of nephrotic syndromes genetically transmitted and that may be congenital, present in the first year of life or in the older child, are attributable to NPHS1, NPHS2, WT1 and KLAMB2 gen mutations. Other nephrotic syndromes produced by genetic mutations may not appear until adulthood. The main objective of present review was to alert on the nephrotic syndromes produced by genetic mutations without response to immunosuppressive treatments, but on those in which such treatment may be dangerous for patient

Progress in congenital nephrotic syndrome / 国际儿科学杂志

Congenital nephrotic syndrome,the common cause of end stage renal disease in chidren,is a rare kidney disorder.With the advanced molecular biology,much progress have been made in its etiology,diagnosis and treatment.This paper will mainly focus on its classification,diagnosis and therapy.

Two Korean Infants with Genetically Confirmed Congenital Nephrotic Syndrome of Finnish Type

Congenital nephrotic syndrome is defined as nephrotic syndrome which manifests in utero or during the first 3 months of life. The prototype of congenital nephrotic syndrome is congenital nephrotic syndrome of Finnish type (CNF, OMIM #602716), which is caused by loss-of-function mutations of the nephrin gene (NPHS1). There have been few clinical case reports of CNF in Korea, but none of which was confirmed by genetic study. Here, we report two children with congenital nephrotic syndrome. Genetic analysis of the NPHS1 gene revealed compound heterozygous frame-shifting mutations (c.2156_2163 delTGCACTGC causing p.L719DfsX4 and c.3250_3251insG causing p.V1084GfsX12) in one patient and a missense mutation (c.1381G>A causing p.R460Q) and a nonsense mutation (c.2442C>G causing p.Y814X) in the other patient. The nonsense mutation was novel. The clinical courses of the patients were typical of CNF. This is the first report of genetically confirmed CNF in Korea to date. The early genetic diagnosis of CNF is important for proper clinical management of the patients and precise genetic counseling of the families.

Early Onset Renal Failure in Congenital Nephrotic Syndrome associated with Congenital Diaphragmatic Hernia by WT1 Gene Mutation

We experienced a female neonate with congenital nephrotic syndrome (CNS) associated with congenital diaphragmatic hernia (CDH). Because of the rare combination of two conditions, we report this case with literature review. CDH was found immediately after birth and emergency operation was done for hernia repair. But on the next day, generalized edema and oliguria(0.59 mL/kg/hour) was found and her blood chemistry showed hypoalbuminemia (1.6 g/dL), increased BUN (27.7 mg/dL) and serum creatinine( 1.8 mg/dL) along with heavy proteinuria (4+). We started albumin infusion with a bolus of intravenous furosemide. We suspected the neonate had congenital nephrotic syndrome and her 24hr urine protein was 1,816 mg/day. In spite of immunosuppressive therapy, the nephrotic syndrome and renal failure progressed. We started peritoneal dialysis on the day of life 22 but it was not satisfactory. She was complicated by intracranial hemorrhage and multi-organ failure and expired at 34 days of age. Kidney necropsy was performed which showed diffuse mesangial sclerosis (DMS). Her chromosome study revealed 46, XX and her gene study revealed a heterozygous missense mutation, Arg366His, in Wilms tumor suppressor gene (WT1). This case deserves attention on account of the 4th case of CNS with CDH revealing the Arg366His mutation in the WT1 gene andG the 1st case of early onset renal failure without male pseudohermaphroditism and Wilms tumor with CNS, CDH and the Arg366His mutation in the WT1 gene. So, this report gives support to the hypothesis that Arg366His mutation in the WT1 gene can result in CNS and CDH.

Clinical Evaluation of Nephrotic Syndrome Manifesting in the First Year of Life

PURPOSE: This study was performed to report the diagnosis and treatment of nephrotic syndrome manifesting in the first year of life. METHODS: We retrospectively reviewed the clinical data with chart review in 7 patients who were diagnosed as nephrotic syndrome manifesting in the first year of life from 1996 to 2007. RESULTS: Three patients had congenital nephrotic syndrome, the other 4 patients had infantile nephrotic syndrome. Their ages ranged from birth to 11 months and male to female ratio was 1 to 6. Renal biopsies were done in 6 patients. One patient had Finnish type congenital nephrotic syndrome, 2 patients had diffuse mesangial sclerosis, 2 patients had focal segmental glomerulosclerosis and 1 patient had minimal change disease. Genetic analyses of NPHS2, PLCE1, and WT1 were done in 4 patients and 2 of them had WT1 mutation. Among 3 patients with congenital nephrotic syndrome, 1 patient was diagnosed as congenital nephrotic syndrome of Finnish type and the other 2 patients were diagnosed as Denys-Drash syndrome. All of the patients with congenital nephrotic syndrome died due to sepsis. Among 4 patients with infantile nephrotic syndrome, 2 patients died and 1 had remission, another patient progressed to end stage renal disease. CONCLUSION: Most of nephrotic syndrome manifesting in the first year was hereditary renal disease. Patients with nephrotic syndrome manifesting in the 3 month of life had poorer prognosis and needed more aggressive management including early dialysis and renal transplantation might be considered compared with infantile nephrotic syndrome. Further genotype-phenotype correlation studies are needed.

Galloway-Mowat Syndrome in Two Siblings

We report on two Korean siblings with multiple congenital anomalies : microcephaly, gyral abnormality, minor facial anomalies, and congenital nephrotic syndrome. The first infant developed proteinuria at age 3 days. This condition appeared similar to that described by Galloway and Mowat and reviewed by Cooperstone, et al, especially the presence of abnormal gyral patterns. She died at 19 months. The second infant; the brother of the first baby had a very similar condition. These two cases may represent the first cases of Galloway-Mowat syndrome in the Korean population.

Congenital Nephrotic Syndrome / 대한신장학회잡지

Congenital nephrotic syndrome(CNS) is a rare disease defined by nephrotic syndrome at birth or within the 1st year of life. This study is performed to investigate a classification based on clinicopathology and to evaluate the clinical course and prognosis according to types of CNS. We performed retrospective clinical study with chart review in 8 patients who were diagnosed as CNS from 1980 to 1995. The results were as follows: Their ages at the onset of illness ranged from birth to 7 months (median 2.2 months) and there were 7 males and 1 female. There were proteinuria, hypoalbuminemia and edema in all cases, accompanied with ascites(7cases), hematuria(5cases), hepatosplenomegaly(2cases), umbilical hernia(1case) and inguinal hernia(1case). A classification of these based on clinicopathology showed CNS of Finnish type in 2 patients, congenital syphilitic nephrotic syndrome in 2, mesangial glomerulosclerosis, minimal change disease, Drash syndrome and undefined CNS in 1 each. Of the 8 patients with CNS, 3 died of sepsis and renal failure, 1 responded to steroid and cyclosporin therapy and is alive at 20 months, 1 responded to penicillin, 1 discharged voluntarily, and 2 were lost to follow-up. In conclusion, it had been considered that all forms of CNS except the secondary ones have a very poor prognosis. But if the appropriate management including early renal transplantation is established under the definite diagnosis which is based on clinicopathology, we can expect long term survival, normal growth and development for the child of CNS.