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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the</span><span class="elsevierStyleBold"> </span><span class="elsevierStyleBold">Editor&#44;</span></p><p class="elsevierStylePara">Congenital nephrotic syndrome &#40;CNS&#41; is a serious&#44; rare disease which in most cases has autosomal recessive monogenic inheritance&#46; Several genes are implicated&#44; the most frequent of which are NPHS1&#44; NPHS2&#44; WT1 and LAMB2&#46;<span class="elsevierStyleSup">1&#44;2</span> It manifests clinically with massive proteinuria&#44; general oedema&#44; hypoalbuminaemia and hypertriglyceridaemia appearing in the first three months of life&#46;<span class="elsevierStyleSup">3</span> Here&#44; we present the first case of a CNS patient with multigenic alteration of three of the four most common genes&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE REPORT</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Our patient was a one-month-old male from Morocco&#44; who came to the Emergency department after presenting symptoms such as vomiting&#44; rejection of food and abdominal distension which had lasted 4 days&#46; The pregnancy was controlled&#44; with no relevant obstetric or perinatal history&#46; The baby was born full-term with the proper weight for his gestational age&#46; On examination the patient&#8217;s general condition was fair&#44; with cutaneous-mucous paleness and general oedema predominant in the lower limbs&#46; A grade IV&#47;VI polyfocal systolic murmur was auscultated&#46; The abdomen was distended&#44; with the presence of the superficial venous system and ascites&#46; Laboratory analyses revealed normocytic-normochromic anaemia&#44; leukocytosis with a normal formula&#44; creatinine below 0&#46;2mg&#47;dl and 10mg&#47;dl urea&#44; high cholesterol and triglycerides&#44; and reduced total proteins and albumin&#44; as well as hyponatraemia&#44; hypopotassaemia and hypocalcaemia &#40;Table 1&#41;&#46; The parathyroid hormone was slightly high&#46; The patient&#8217;s urine presented nephrotic-range proteinuria with a urine protein&#58;creatinine index of 33&#46;7&#46;</p><p class="elsevierStylePara">When CNS was suspected&#44; the patient began to undergo intensive diuretic and antiproteinuric therapy&#44; antithrombotic prophylaxis&#44; adjuvant treatment with alfacalcidol&#44; iron&#44; calcium carbonate and levothyroxin&#44; as well as enteral nutrition with hyperprotein&#44; hypercaloric formula&#46; He required treatment with serum albumin and erythropoietin&#46; Moderate pulmonary valve stenosis and atrial septal defect were diagnosed in the cardiology study&#46; The genetic study revealed mutations of the frameshift type for the NPHS1 gene&#44; of the intronic variant type for the NPHS2 gene and of the missense type for the WT1 gene&#46;</p><p class="elsevierStylePara">At three months of age he was readmitted due to convulsive status epilepticus secondary to severe hypocalcaemia&#46; The high quantities of intravenous calcium which needed treatment via peripheral venous access caused a third-degree burn which required a cutaneous graft to be placed&#46;</p><p class="elsevierStylePara">Intensive care was required on two occasions&#44; at 4 and 6 months of age&#44; for sepsis secondary to <span class="elsevierStyleItalic">Staphylococcus hominis</span> and <span class="elsevierStyleItalic">Enterococcus faecalis</span> respectively&#44; which were resolved with empirical antibiotic treatment and then according to the results of the antibiogram&#46;</p><p class="elsevierStylePara">Finally&#44; the patient died at 8 months of age due to bilateral pneumonia linked to pneumothorax with decompensation of the underlying pathology which caused refractory hypoxaemia&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">CNS may be suspected in the prenatal period due to high levels of alphaphetoprotein&#44; maintaining normal figures for cholinesterase from the 15<span class="elsevierStyleSup">th</span> week of gestation in amniotic fluid and maternal blood&#46;<span class="elsevierStyleSup">2&#44;4</span> At birth the link between premature birth and a large placenta can provide guidance&#44;<span class="elsevierStyleSup">5</span> factors which were not present in our patient&#46;</p><p class="elsevierStylePara">The most frequent cause of this condition is the NPHS1 gene mutation&#44; with autosomal recessive inheritance&#44; responsible for encoding nephrin&#46;<span class="elsevierStyleSup">2&#44;5&#44;6</span> This alteration is particularly common in Finland&#44; therefore it has been referred to as CNS of the Finnish type&#46; The NPHS2 gene encodes the protein podocin and is the most common cause of cortico-resistance in childhood&#46;<span class="elsevierStyleSup">7</span> The WT1 gene plays a crucial role in the embryonic development of the kidney and the genitals and has been linked to the presence of syndromes such as WAGR&#44; Denys-Drash and Frasier&#46;<span class="elsevierStyleSup">1&#44;8</span> It is considered a monogenic condition and no cases have been described in the literature of more than two genes being implicated&#44; therefore the clinical-pathological importance of the finding we have made in this case is not known&#46;</p><p class="elsevierStylePara">The method of choice for its diagnosis is genetic analysis&#44; although first secondary causes have to be discarded&#44; such as congenital infections&#44; autoimmune diseases or exposure to toxins during pregnancy&#46;<span class="elsevierStyleSup">9</span> Knowing this can be useful in the patient&#8217;s treatment&#44; prognosis and monitoring&#44; and is key to offering genetic counselling to the family&#46;<span class="elsevierStyleSup">10</span> Renal biopsy does not reveal the causes of CNS&#44; as histological findings can occur in various conditions&#46;<span class="elsevierStyleSup">2</span> CNS is not normally linked to heart malformations&#44; with the exception of a high frequency of ventricular hypertrophy&#46;<span class="elsevierStyleSup">11</span> Our patient presented pulmonary valve stenosis and atrial septal defect&#44; defects scarcely written about in the literature&#46;</p><p class="elsevierStylePara">The most frequent complications are bacterial infections&#44; especially gram-negative microorganisms&#46;<span class="elsevierStyleSup">2</span> Our patient presented two septic infections due to gram-positive bacteria&#44; findings that are less frequent but nonetheless described in other publications&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">The number of hospitalizations in these patients continues to be very high because it is difficult to treat and leads to complications&#44; which reduces the patient&#8217;s quality of life&#46;<span class="elsevierStyleSup">12</span> It is possible that multigenic involvement might entail greater clinical severity&#44; but as there are no findings similar to ours in the literature we cannot confirm these speculations&#46; The aim of treatment is to control the oedema&#44; prevent and treat complications&#44; and provide adequate nutrition to maximize growth and delay replacement therapy&#44; although&#44; in the majority of cases&#44; kidney transplantation is the only curative method of treatment&#46;<span class="elsevierStyleSup">3&#44;5&#44;6</span></p><p class="elsevierStylePara">In conclusion&#44; CNS is a rare&#44; severe pathology that is difficult to treat&#44; the causes of which can include various genes&#44; which may have important implications on clinical severity and associated complications&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12157&#95;16025&#95;56742&#95;en&#95;t1&#95;12157&#46;jpg" class="elsevierStyleCrossRefs"><img src="12157_16025_56742_en_t1_12157.jpg" alt="Analytical parameters upon admission&#46;"></img></a></p><p class="elsevierStylePara">Table 1&#46; Analytical parameters upon admission&#46;</p>"
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