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.

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.

RESUMO A Síndrome Nefrótica (SN) idiopática em crianças pode, raramente, complicar-se. O tromboembolismo é uma das complicações mais raras, principalmente no primeiro episódio, e de diagnóstico mais difícil, uma vez que a clínica pode ser inespecífica. Descrevemos o caso de uma criança de 5 anos com episódio inaugural de SN, destacando-se hipoalbuminemia inicial grave (< 2g/dL). Apresentou fraca resposta inicial à corticoterapia e, após 8 dias de internamento, iniciou quadro de cefaleias e vômitos, sem alterações hemodinâmicas, sem febre, sem exantema e com exame neurológico normal. Perante a suspeita de hipertensão intracraniana, foi realizada TC-CE, que mostrou trombose venosa cerebral (TVC). Foi então iniciada terapêutica anticoagulante com posterior boa evolução clínica. Trata-se de uma criança sem fatores de risco pró-trombóticos evidentes. Desde o diagnóstico, teve 3 recaídas, uma das quais com níveis baixos de antitrombina, que no episódio inaugural eram normais, apesar de avaliados já numa fase não proteinúrica. Suspeita-se, assim, que esse déficit plasmático em antitrombina na recaída poderá mimetizar a queda plasmática inicial, hipótese também apoiada pela hipoalbuminemia grave ao diagnóstico. Esta trombofília grave adquirida poderá ter sido mecanismo etiológico para a trombose venosa cerebral. O interesse deste caso prende-se com a raridade de complicações tromboembólicas na SN Pediátrica, ainda mais raras no episódio inaugural. Nesse caso, a boa evolução foi possível após a associação da terapêutica anticoagulante. Embora sem fatores de risco iniciais evidentes, a evolução do caso permitiu a suspeita de uma trombofília adquirida grave como mecanismo fisiopatológico do tromboembolismo cerebral.

ABSTRACT Complications are rare in pediatric cases of idiopathic nephrotic syndrome (NS). Thromboembolism ranks among the most uncommon and difficult complications to diagnose, particularly in the first episode of NS, since clinical signs might be unspecific. This report describes the case of a 5-year-old girl with NS for the first time presenting with severe hypoalbuminemia (< 2g/dL). The patient responded poorly to therapy with corticosteroids. On day 8 of hospitalization she started having headaches and vomiting; she did not present hemodynamic alterations, fever or exanthems, and her neurological parameters were normal. The patient was suspected for intracranial hypertension, and computed tomography scans revealed she had cerebral venous sinus thrombosis (CVST). She was started on anticoagulants and showed clinical signs of improvement. The patient had no evident prothrombotic risk factors. She had three other episodes since she was diagnosed, one in which her plasma antithrombin level was low. Although antithrombin levels were normal in her first episode, she was tested after the resolution of proteinuria. The low levels of antithrombin seen in the first recurrence might have mirrored the initial drop in plasma antithrombin levels, an idea supported by the severe hypoalbuminemia she had when diagnosed. This severe manifestation of acquired thrombophilia might be in the origin of CVST. This report presents a rare case of thromboembolic complication in a pediatric patient with NS. The patient progressed well since she was started on anticoagulants. Although she did not present any evident risk factors at first, the development of her case indicated that severe acquired thrombophilia might have worked as the pathophysiological mechanism leading to CVST.

Introduction. Rickets is a paediatric disease which should be suspected in children presenting with failure to thrive, motor developmental delay and orthopaedic abnormalities. Although rare, hereditary hypophosphataemic rickets is the most common form of heritable rickets. Patients and Methods. Retrospective observational study of all children with hypophosphataemic rickets observed at a paediatric nephrology unit of a tertiary paediatric hospital from 1982 to 2012, identified from the unit’s database. Data collected included demographics, risk factors, pre-existing medical conditions, clinical, radiographic and laboratory findings, treatment and morbidity. Results. Eleven children with hypophosphataemic rickets were studied, with a median age at admission of 4.25 years (0.66-10.92). Family history of rickets or orthopaedic abnormalities was found in five children. The first clinical manifestations were delayed/abnormal gait (7/11) and short stature (4/11). Skeletal deformities were present in all children: genus valgum or varum (11/11), thickening of the wrists (7/11), rachitic rosary (4/11), frontal skull bossing (2/11), Harrison’s groove (1/11). Dental abscess was reported in one child and joint pain in six. Laboratory findings included increased alkaline phosphatase (11/11), low serum phosphorus (11/11), normal serum calcium (10/11) and parathyroid hormone values (6/11) and low renal phosphorus reabsorption rate (9/10). None of the children had hypercalciuria. All children were treated with oral phosphorus and calcitriol (8/11 with lack of compliance). Seven children were discharged with a median age of 16.5 years; all had bone deformities, 5/7 had short stature and 1/7 had nephrocalcinosis. Discussion. Hypophosphataemic rickets is a rare disease with significant long-term morbidity. It should be suspected in children presenting with short stature, developmental delay and orthopaedic abnormalities. Increased alkaline phosphatase, low serum phosphorus with normal serum calcium and impaired renal tubular reabsorption of phosphate confirm the diagnosis. Early diagnosis and treatment are essential to minimise morbidity in children