[Show abstract][Hide abstract] ABSTRACT: Wilms' tumor type 1 gene (WT1) encodes a zinc-finger transcription factor that plays a key role during genitourinary development and in adult kidney. Mutations in exons 8 and 9 are associated with Denys-Drash Syndrome, whereas those occurring in the intron 9 donor splice site are associated with Frasier Syndrome. Familial cases of WT1 mutations are rare with only few cases described in the literature, whereas cases of WT1 mutations associated with isolated nephrotic proteinuria with or without focal segmental glomerular sclerosis (FSGS) are even rarer. Exons 8 and 9 of WT1 gene were analyzed in two non-related female patients and their parents. Patient 1, who presented with isolated nephrotic proteinuria and histologic pattern of FSGS, is heterozygous for the mutation c.1227+4C>T. This mutation was inherited from her mother, who had undergone kidney transplant due to FSGS. Patient 2 is heterozygous for the novel c.1178C>T transition inherited from her father. The putative effect of this nucleotide substitution on WT1 protein is p.Ser393Phe mutation located within the third zinc-finger domain. The patient and her father presented, respectively, isolated nephrotic proteinuria and chronic renal failure. These data highlight the importance of the inclusion of WT1 gene mutational analysis in patients with isolated nephrotic proteinuria, especially when similar conditions are referred in the family.
Biochemical and Biophysical Research Communications 10/2013; 441(2). DOI:10.1016/j.bbrc.2013.10.064 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Frasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis. Arq Bras Endocrinol Metab. 2012;56(8):525-32.
Arquivos brasileiros de endocrinologia e metabologia 11/2012; 56(8):525-32. DOI:10.1590/S0004-27302012000800011 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pain induced by calcineurin inhibitors is a rare complication of unknown pathogenesis. We have reported herein a 7-year-old child who presented with abdominal pain, vomiting, and weight loss showing no significant findings after an extensive laboratory and imaging workup. After conversion from tacrolimus to sirolimus, there was complete resolution of the gastrointestinal symptoms and pain; the patient displays excellent renal function. Calcineurin inhibitor-induced pain syndrome is diagnosis of exclusion but must be considered because the withdrawal of this immunosuppressive agent is associated with improvement in symptoms and quality of life.
[Show abstract][Hide abstract] ABSTRACT: OBJETIVO: avaliar o desempenho da haste extensível ancorada por ganchos (HIMEX) em deformidades da osteogênese imperfeita (OI). MÉTODOS: Todas as crianças operadas com HIMEX entre 1990 - 2004. Foi comparado o número de fraturas, reaparecimento de deformidades e capacidade de deambulação antes e após a HIMEX; incidência de migração e sobrevida da haste por curvas de sobrevivência. RESULTADOS: 14 pacientes (2 a 18 anos), oito do sexo feminino, incluindo 46 procedimentos, 39 primários e sete re-operações. Idade média na primeira fratura de 148,21 dias e média de 42,6 fraturas/paciente pré colocação da HIMEX. Dos 46 procedimentos, 28 no fêmur e 18 na tíbia. Tempo médio de seguimento de 80,21 ± 36,71 meses. Houve diminuição significativa de fraturas/paciente (0,78) e melhora na deambulação em sete dos 14 pacientes. Porcentagem de re-operação de 18% e migração do implante em 12% (05/39). 80 % dos implantes in situ até 108 meses. Implantes na tíbia tiveram sobrevida significativamente menor que os do fêmur. O tipo da OI e a idade na época da cirurgia não influenciaram significativamente a incidência de re-operação. CONCLUSÃO: A HIMEX levou à redução significativa no número de fraturas, incidência menor de migração e sobrevida maior da haste do que a referida na literatura.
[Show abstract][Hide abstract] ABSTRACT: The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.
Arquivos brasileiros de endocrinologia e metabologia 12/2008; 52(8):1277-81. DOI:10.1590/S0004-27302008000800012 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mutations in the vitamin D receptor (VDR) are associated to the hereditary 1,25-dihydroxivitamin D-resistant rickets. The objectives of this work are: search for mutations in the VDR and analyze their functional consequences in four Brazilian children presented with rickets and alopecia. The coding region of the VDR was amplified by PCR e direct sequenced. We identified three mutations: two patients had the same mutation in exon 7 at aminoacid position 259 (p.Q259E); one patient had a mutation in exon 8 at codon 319 (p.G319V) and another one had a mutation in exon 3 leading to a truncated protein at position 73 (p.R73X). Functional studies of the mutant receptors of fibroblast primary culture, from patients' skin biopsy treated with increasing doses of 1,25(OH)2 vitamin D showed that VDR mutants were unable to be properly activated and presented a reduction in 24-hydroxylase expression level.
Arquivos brasileiros de endocrinologia e metabologia 12/2008; 52(8):1244-51. DOI:10.1590/S0004-27302008000800007 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growth failure is frequent and a clinically important issue in children with chronic kidney disease (CKD). Many factors contribute to impaired growth in these children, including abnormalities in the growth hormone (GH)--insulin-like growth factor 1 (IGF-1) axis, malnutrition, acidosis, renal bone disease and glucocorticoid associated treatment. The management of growth failure in children with CKD is complicated by the presence of other-disease related complications requiring medical intervention. Despite evidence of GH efficacy and safety in this population, this therapy is still underutilized. This review shows the impact, the causes and the treatment of growth failure in children with CKD.
Arquivos brasileiros de endocrinologia e metabologia 08/2008; 52(5):783-91. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze the changes in IGF-1, IGFBP-3, leptin and insulin after replacement doses of recombinant human growth hormone (rhGH) in short prepubertal children with chronic renal failure (CRF).
Eleven children (3F:8M), with mean age of 9.6 years, were treated with rhGH (0.23 mg/Kg weekly for 12 months). Serum leptin, insulin, glucose, IGF-1 and IGFBP-3 were measured before, 6 and 12 months after beginning rhGH treatment.
The serum levels of leptin, insulin and glucose did not vary during the treatment; normal leptin and glucose levels and high insulin were observed. There was a significant increment of IGF-1 and IGFBP-3 during the use of rhGH.
The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: To describe the case of a child with paracoccidioidomycosis who presented hypercalcemia with multiple osteolytic lesions.
A 6-year-old boy was admitted with a one-month history of fever and hepatosplenomegaly. On admission, he looked sick, pale, and had disseminated lymphadenopathy and hepatosplenomegaly. The laboratory findings included anemia (hemoglobin = 6.8 g/dl), eosinophilia (1,222/mm3), thrombocytopenia (102,000/mm3), and hypoalbuminemia (serum albumin = 2.2 g/dl). Paracoccidioides brasiliensis was identified in bone marrow examination. In the second week after admission, the patient presented joint pain, poor activity and difficulty in walking. He presented hypercalcemia (maximum value = 14.9 mg%) and reduction in renal function, which lasted for two weeks. On the 42nd day after admission, his chest X-ray showed lytic lesions in clavicle, scapula, ribs, and humerus, with bilateral slipped capital humeral epiphysis. The patient presented nephrocalcinosis and nephrolithiasis, reduction in creatinine clearance and evidence of tubular lesions. At the end of the second month after admission, Mycobacterium tuberculosis was isolated in gastric washing. The child received treatment for paracoccidioidomycosis and tuberculosis and has not had any sequelae for 3 years.
The development of symptomatic hypercalcemia leading to renal lesion, associated with multiple osteolytic lesions, had never been described in paracoccidioidomycosis. Although pulmonary tuberculosis was diagnosed and could be related to hypercalcemia, the sudden onset of hypercalcemia and its normalization without specific treatment for tuberculosis suggests that bone lysis was the most important factor in the genesis of hypercalcemia.
Jornal de Pediatria 07/2005; 81(4):349-52. DOI:10.2223/JPED.1375 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atualmente, é grande o impacto psicossocial da baixa estatura nas crianças e adolescentes com insuficiência renal crônica (IRC), sendo o hormônio de crescimento recombinante humano (rhGH) uma alternativa terapêutica. Avaliamos o crescimento e a composição corporal (CC) em 11 crianças pré-púberes (9M/2F; 3,5-12,8a) com IRC e baixa estatura e/ou baixa velocidade de crescimento, tratadas com rhGH (0,7-1,0UI/Kg/semana) por 18 meses. Avaliamos antropometria e CC por impedância bioelétrica tetrapolar antes e 6, 12 e 18 meses após o início do rhGH; maturação esquelética e função renal foram avaliadas antes e após 6 e 12 meses. Houve aumento significativo do peso, da altura, da VC e da massa magra (MM), com diminuição significativa da massa gorda (MG) no período de 0 a 6 meses de tratamento. Entre 0 e 12 meses houve apenas aumento significativo da altura. Entre 6 e 12 meses houve inversão da CC, com diminuição significativa da MM e aumento da MG. Entre 12 e 18 meses houve restabelecimento da CC inicial, com diminuição significativa da MG e aumento da MM. Não se observaram alterações na função renal, nem avanço exagerado da maturação esquelética. Em conclusão, o rhGH em doses de reposição por 18 meses promoveu melhora do crescimento com mudança da CC neste grupo de crianças com IRC, especialmente nos primeiros 12 meses de tratamento, sem efeitos colaterais. (Arq Bras Endocrinol Metab 2002;46/6:661-667)
[Show abstract][Hide abstract] ABSTRACT: A desnutrição está freqüentemente relacionada com doenças crônicas. O diagnóstico precoce realizado por técnicas práticas e simples favorece o tratamento, minimizando as complicações. OBJETIVO: avaliar a situação nutricional de crianças e adolescentes com insuficiência renal crônica (IRC) utilizando parâmetros antropométricos. MÉTODOS: Foram avaliadas 41 crianças e adolescentes com IRC ("clearance" de creatinina abaixo de 50 ml/min/1,73m2) acompanhadas no Ambulatório de Nefrologia Pediátrica do HC-Unicamp, de janeiro de 1995 a novembro de 1996, pelas medidas do perímetro braquial (PB) e da prega cutânea tricipital (PCT), com as quais calculou-se a área de gordura braquial (AGB) e área muscular braquial (AMB) e os respectivos escores z. Estas medidas foram realizadas pelo menos duas vezes, com intervalo de 0,21 a 1,3 anos (0,88 ± 0,04). RESULTADOS: Os escores z obtidos tanto para PB, como para PCT, AGB e AMB apresentaram valores muito baixos, sendo que, na evolução, apenas o escore z de AMB apresentou melhora estatisticamente significativa (p= 0,03 teste de Wilcoxon). Quando selecionados quanto ao tratamento de substituição renal, apenas os transplantados renais apresentaram melhora estatisticamente significativa para o escore z de PB (p= 0,02 teste de Wilcoxon). CONCLUSÃO: Estes dados mostram uma situação nutricional comprometida tanto em relação à reserva de gordura, quanto de músculo, com melhora no acompanhamento apenas em relação à área muscular.
Revista da Associação Médica Brasileira 06/2001; 47(2):137-140. DOI:10.1590/S0104-42302001000200032 · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: the purpose of this study is to evaluate the nutritional status of children and teenagers with chronic renal (CRF) failure using anthropometric measurements.
41 children and adolescents with (CRF) (creatinine "clearance" < 50 ml/min/1,73m(2)) followed at the Pediatric Nephrology Unit (HC-UNICAMP), between January 1995 and November 1996, were evaluated by the assessment of anthropometric measurements, mid upper arm circunference (MUAC) and triceps skinfold (TSF). With these measurements, mid arm fat area (MUAFA) and arm muscle area (AMA) were calculated and its z-scores. These measurements were performed twice at least, ranging from 0.21 to 1.3 years (0.88 +/- 0.04).
all the z-scores (MUAC, TSF, MUAFA and AMA) were very low, and only the AMA z-score was statistically significant (p= 0,03 Wilcoxon test). The patients were divided in to groups, according to their treatment, and the MAC z-score for the renal transplantation group was statistically significant (p= 0,02 Wilcoxon test).
these data demonstrate a compromised nutritional status from both muscle and fat stores, with an improvement in muscle stores.
Revista da Associação Médica Brasileira 01/2001; 47(2):137-40. · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Considering that the brain abscess is rare in infants, with a high mortality rate, the objective of this paper is to report the clinical evolution of ten children with the diagnosis of brain abscess in the Pediatric Nursery of the Hospital das Clínicas of the Medical School of the Campinas State University (UNICAMP).METHODS: The data of the patients with diagnosis of brain abscess recorded between January 1986 and July 1995 were reviewed. The following data were analyzed: age, sex, clinical manifestations, physical examination, radiological data, etiological agent, treatment, complications and clinical evolution of the patients.RESULTS: The age of the patients varied from 2 to 13 years (median 3 years); 6 of them were female. The neurological manifestations predominated, and 2 patients had history of prior otorhinolaryngological infection (chronic otitis media and sinusitis). Two patients had congenital cyanogenic cardiopathy (Fallot tetralogy and Pulmonary Stenosis with Interventricular Communication). The diagnosis and follow-up were made with computed tomography of the brain. In six cases there were one sole abscess located more frequently in the frontal lobe. The treatment in majority of the cases was broad-spectrum antibiotic association and surgical drainage. Five patients had neurological sequelae (seizure, hydrocephalus and paresis); one death occurred.CONCLUSIONS: Although rare, the brain abscess has to be remembered in patients that have neurological alterations associated to risk factors, as otorhinolaryngological infections and congenital cyanotic cardiopathy, being mandatory the realization of computed tomography of the brain to confirm the diagnosis.
Jornal de pediatria 01/1998; 74(1):62-6. DOI:10.2223/JPED.414 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The gastric emptying of watery meals was studied in 112 male Wistar rats. The meals utilized were saline and glucose-saline solutions whose emptying was assessed 10 and 30 minutes after administration. A liquid 5% glucose meal and a 0.25 M sodium bicarbonate meal were assessed after 30 minutes and a commercial meal was assessed after 60 minutes. For each study time eight control animals and eight animals bilaterally nephrectomized 48 hours before the gastric emptying tests were used. The meals were labeled with red phenol and the gastric residue was determined by standard methodology. A blood sample to determine serum creatine and blood gases analysis was obtained from 22 animals of the control group and the same number of nephrectomized animals. At the time of the gastric emptying tests, the nephrectomized animals had significantly higher levels of creatinine and moderate metabolic acidosis. Results for the saline meal showed that at 10 minutes there was a significant delay in emptying in animals with renal insufficiency. Results for the glucose-saline meal were similar to the saline alone group, except that they did not differ significantly between the control group and the nephrectomized groups. There was a significant delay in the emptying of all the other meals in the animals with renal insufficiency. These data suggest that uremia does not lead to serious disturbances in gastric motility, but that it does interfere with the mechanisms controlling gastric emptying.
Arquivos de Gastroenterologia 01/1998; 35(4):278-82.