Abstract Dent disease is a rare X-linked progressive renal disease characterized by hypercalciuria and low molecular weight proteinuria. In early childhood, patients may manifest only proteinuria and/or hypercalciuria, both of which are generally asymptomatic. The authors report three cases of male patients with asymptomatic, non-orthostatic nephrotic proteinuria first detected during screening for an acute condition. All had intermittent hypercalciuria, one had nephrocalcinosis, and one had mild hypotonia and some learning difficulties. Genetic testing identified pathogenic variants in all patients, two in the OCRL gene and one in the CLCN5 gene. To date, none have developed chronic kidney disease. The diagnosis of Dent disease can be challenging, but it should be considered in all men with unexplained proteinuria. This approach may not only allow for earlier diagnosis, but also avoid unnecessary testing and potentially harmful treatments. Xlinked X linked childhood andor or asymptomatic nonorthostatic non orthostatic condition nephrocalcinosis difficulties CLCN date challenging treatments

Resumo A doença de Dent é uma tubulopatia rara e progressiva ligada ao cromossoma X, caracterizada por hipercalciúria e proteinúria de baixo peso molecular. Na primeira década, os doentes manifestam apenas proteinúria e/ou hipercalciúria, sendo ambas geralmente assintomáticas. Posteriormente, os sintomas podem evoluir para insuficiência renal crónica. São apresentados três casos de crianças do sexo masculino com proteinúria nefrótica não ortostática assintomática detetada em contexto de doença aguda. Todas as crianças apresentaram hipercalciúria intermitente, uma apresentou nefrocalcinose e outra hipotonia ligeira e dificuldades de aprendizagem. O estudo genético identificou variantes patogénicas em todos os doentes, duas no gene OCRL e uma no gene CLCN5. Nenhum doente apresentou deterioração da função renal. O diagnóstico de doença de Dent pode ser desafiante, devendo ser considerado em casos de proteinúria inexplicável no género masculino. Esta abordagem permitirá, não só antecipar o diagnóstico, como evitar investigação e tratamentos desnecessários. X molecular década eou ou assintomáticas Posteriormente crónica aguda intermitente aprendizagem CLCN5 CLCN desafiante permitirá desnecessários

ABSTRACT Hypomagnesemia type I is a rare autosomal recessive disorder characterized by severe hypomagnesemia, often accompanied by hypocalcemia. This disease is caused by mutations in the TRPM6 gene (which encodes the respective channel), leading to reduced intestinal absorption of magnesium and increased renal excretion due to a defect in reabsorption in the distal convoluted tubule. It usually manifests itself in the first months of life, with symptoms of neuromuscular hyperexcitability and seizures, refractory to antiepileptic therapy. Treatment consists of administering high doses of magnesium throughout life. Here, we report a case of hypomagnesemia type I with a novel pathogenic variant of TRPM6 in a 5-month-old girl who developed refractory seizures due to hypomagnesemia.

ABSTRACT Membranoproliferative glomerulonephritis is a rare chronic glomerulonephritis in pediatric age. It may be a primary disorder or secondary to other chronic diseases. Diagnose of membranoproliferative glomerulonephritis is based on specific kidney biopsy findings. The prognostic factors, the outcome and the most suitable treatment regimen are incompletely known in children. We report a case of a 3-year-old boy that presented with nephritic/nephrotic syndrome and hypocomplementemia. After 10 days under corticosteroid therapy, he maintained worsening of renal function and a renal biopsy specimen revealed a membranoproliferative glomerulonephritis. Autoimmune disease and infections were initially excluded, but further investigation revealed positive Polymerase Chain Reaction for cytomegalovirus in blood and urine. Cytomegalovirus genome at biopsy was not identified. He completed six months of treatment with valganciclovir and corticosteroids with total remission of proteinuria and undetected viral loads. With this case, we would like to draw attention to a type of nephropathy that is rare in childhood.

Resumo Histórico A psoríase é uma doença crônica imunomediada que afeta principalmente a pele tanto em adultos quanto em crianças, mas também pode ter envolvimento sistêmico, particularmente com artrite e lesão renal. A nefropatia por IgA é o distúrbio renal mais frequentemente associado à psoríase. Aproximadamente um terço de todos os casos de psoríase começam na infância, mas a associação entre psoríase e distúrbios renais tem sido pouco relatada em pacientes pediátricos. A Púrpura de Henoch-Schönlein (PHS) é uma vasculite sistêmica caracterizada por depósitos de IgA nas paredes dos vasos de órgãos afetados e no mesângio do rim. A histopatologia da nefrite da PHS é idêntica à da nefropatia por IgA. Relato de caso Um menino de 6 anos de idade com início recente de psoríase desenvolveu PHS com envolvimento renal, clinicamente manifestado por proteinúria nefrótica e hematúria. A biópsia renal revelou crescentes fibrocelulares glomerulares e depósitos mesangiais de IgA compatíveis com a nefropatia por IgA. O tratamento com corticosteróides sistêmicos levou ao controle da hematúria, mas como a proteinúria nefrótica persistiu, a ciclofosfamida foi adicionada, levando a uma diminuição gradual da proteinúria. Conclusões Propomos um mecanismo comum subjacente na patogênese tanto da PHS quanto da psoríase, envolvendo uma desregulação da resposta imune mediada por IgA, que poderia predispor a ambas as entidades, bem como a danos renais e nefropatia por IgA nesses pacientes.

Abstract Background Psoriasis is a chronic immune-mediated disorder that primarily affects the skin in both adults and children but can also have systemic involvement, particularly with arthritis and kidney injury. IgA nephropathy is the most frequent kidney disorder associated with psoriasis. Approximately one third of all cases of psoriasis begin in childhood, but association between psoriasis and renal disorders has scarcely been reported in pediatric patients. Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA deposits in the vessel walls of affected organs and in the mesangium of the kidney. HSP nephritis histopathology is identical to IgA nephropathy. Case report A 6-year-old boy with recent onset of psoriasis developed HSP with kidney involvement, clinically manifested by nephrotic-range proteinuria and hematuria. Kidney biopsy revealed fibrocellular glomerular crescents and mesangial IgA deposits compatible with IgA nephropathy. Treatment with systemic corticosteroids led to the control of hematuria, but as nephrotic-range proteinuria persisted, cyclophosphamide was added, leading to a gradual decrease in proteinuria. Conclusions We propose an underlying common mechanism in the pathogenesis of both HSP and psoriasis, involving a dysregulation of the IgA-mediated immune response, which could predispose to both entities as well as to kidney damage and IgA nephropathy in these patients.