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Central congenital hypothyroidism (CH) can occur as an isolated deficiency or as part of combined pituitary hormone deficiency. Unlike primary CH, central CH cannot be detected by newborn screening (NBS) using dry filter paper blood TSH levels, and early diagnosis remains challenging. In this study, the clinical and genetic backgrounds of patients with isolated central CH were determined through a questionnaire-based survey among members of the Japanese Society for Pediatric Endocrinology. The known causes of isolated central CH were studied in 14 patients, including six with previously reported patient data. The results revealed IGSF1 and TBL1X pathogenic variants in nine and one patient, respectively. All six patients with low free thyroxine (FT4) levels detected in NBS carried IGSF1 pathogenic variants. Five patients with isolated central CH diagnosed after 3 months of age were variant-negative, except for one female patient with a heterozygous IGSF1 variant. Two of the four variant-negative patients and a variant-positive patient were diagnosed with pituitary hypoplasia. One and two patients with IGSF1 variant had obesity and intellectual disability, respectively. Left amblyopia was identified in the patient with a TBL1X variant. The study revalidated that IGSF1 variants comprise the most frequent pathogenic variant in patients with isolated central CH in Japan. The neonatal period is the optimal time for the diagnosis of central CH, particularly IGSF1 abnormalities, and the introduction of T4 screening should be considered in the future, taking cost-effectiveness into consideration.
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Hipotireoidismo Congênito , Triagem Neonatal , Humanos , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/sangue , Feminino , Japão/epidemiologia , Masculino , Recém-Nascido , Lactente , Proteínas de Membrana/genética , Pré-Escolar , Criança , Imunoglobulinas/sangue , Imunoglobulinas/genética , Mutação , TransducinaAssuntos
Síndrome de DiGeorge , Doença de Graves , Hipocalcemia , Humanos , Hipocalcemia/complicações , Hipocalcemia/diagnóstico , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/genética , Deleção CromossômicaRESUMO
Congenital hyperinsulinism (CHI) is the most common form of persistent hypoglycemia in infants, and diazoxide is the most widely used drug for its treatment. Diazoxide suppresses insulin secretion and attenuates hypoglycemia by binding to sulfonylurea receptor 1 and activating KATP channels. While the short-term side effects of this drug, such as edema and blood cell abnormalities, are well known, the clinical course after its long-term oral administration remains unclear. Furthermore, there are currently no case reports clearly demonstrating a causal relationship between diazoxide and impaired glucose tolerance. We herein describe the case of a 9-year-old girl with CHI complicated with Kabuki syndrome who presented with impaired glucose tolerance due to decreased initial insulin secretion and insulin resistance caused by obesity resulting from diazoxide medication. This is a rare case of the insufficient effects of insulin due to the oral administration of diazoxide, and provides insights for managing the long-term administration of diazoxide to children.
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Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged thyroid gland with multiple nodules, is usually seen in adults and is recognized as a separate disorder from congenital hypothyroidism. Here we performed a linkage analysis of a family with both nongoitrous congenital hypothyroidism and MNG and identified a signal at 15q26.1. Follow-up analyses with whole-genome sequencing and genetic screening in congenital hypothyroidism and MNG cohorts showed that changes in a noncoding TTTG microsatellite on 15q26.1 were frequently observed in congenital hypothyroidism (137 in 989) and MNG (3 in 33) compared with controls (3 in 38,722). Characterization of the noncoding variants with epigenomic data and in vitro experiments suggested that the microsatellite is located in a thyroid-specific transcriptional repressor, and its activity is disrupted by the variants. Collectively, we presented genetic evidence linking nongoitrous congenital hypothyroidism and MNG, providing unique insights into thyroid abnormalities.
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Cromossomos Humanos Par 15 , Hipotireoidismo Congênito , Repetições de Microssatélites , Linhagem , Humanos , Hipotireoidismo Congênito/genética , Repetições de Microssatélites/genética , Feminino , Masculino , Cromossomos Humanos Par 15/genética , Bócio Nodular/genética , Adulto , Glândula Tireoide/patologia , Glândula Tireoide/metabolismo , Ligação GenéticaRESUMO
Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) is characterized by circulating blast cells in the blood. TAM usually resolves spontaneously, but several studies have associated this condition with early death, focusing on the development of effective treatments. We report the case of a neonate with DS who had TAM and novel GATA1 mutation. Although the patient eventually died of hepatic failure, exchange blood transfusion and low-dose cytarabine treatment dramatically improved pulmonary hypertension and acute renal failure refractory to conventional therapy. Such a blast-reducing approach might be useful for improving circulatory disturbances in neonates with DS and TAM.
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Antimetabólitos Antineoplásicos/administração & dosagem , Transfusão de Sangue , Citarabina/administração & dosagem , Síndrome de Down/terapia , Doenças do Recém-Nascido/terapia , Falência Hepática/terapia , Mielopoese , Síndrome de Down/complicações , Síndrome de Down/genética , Evolução Fatal , Fator de Transcrição GATA1/genética , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/terapia , Recém-Nascido , Doenças do Recém-Nascido/genética , Falência Hepática/complicações , Falência Hepática/genética , Masculino , Mutação , Insuficiência Renal/complicações , Insuficiência Renal/genética , Insuficiência Renal/terapiaRESUMO
IGF-binding proteins (IGFBPs) have multiple cellular effects, which occur by both IGF-dependent and -independent mechanisms. IGFBP-2 is involved in the regulation of both normal and carcinogenic cell growth. To further understand the actions of IGFBP-2, we carried out a yeast two-hybrid screen to search for intracellular partner proteins using a human prostate cDNA library. We isolated Pim-1-associated protein-1 (PAP-1)-associated protein-1 (PAPA-1) as an IGFBP-2-binding protein, whose expression and subcellular localization is regulated by both IGFBP-2 and androgens. Coimmunoprecipitation and glutathione S-transferase pull-down assay confirmed the interaction in vitro, and confocal microscopy showed the colocalization of IGFBP-2 and PAPA-1 in the nucleus. Suppression of PAPA-1 by small interfering RNA treatment enhanced the growth-promoting effect of IGFBP-2. Conversely, IGFBP-2-promoted bromodeoxyuridine incorporation into LNCaP cells was abrogated by the simultaneous overexpression of myc-hPAPA-1. Mouse embryonic fibroblasts from IGFBP-2 knockout mouse showed diminished growth activity compared with wild type, and expression of FLAG-mPAPA-1 decreased cell proliferation in IGFBP-2 knockout, but not control mouse embryonic fibroblasts. These studies suggest that the growth-promoting role of IGFBP-2 in prostate cancer is inhibited by its intracellular interaction with PAPA-1.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteínas Nucleares/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Masculino , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética , Proteínas Associadas a Pancreatite , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
Unilateral absence of a pulmonary artery (UAPA) is a rare anomaly. Although UAPA has been reported previously, its age-related pathogenesis and symptoms remain unclear. This retrospective cohort study included cases of UAPA reported in Japan at medical meetings or in the literature from 1990 through 2009. Patients with other congenital cardiac defects were excluded from the study. Clinical status was assessed according to age, and the clinical course of patients with isolated UAPA was compared with that of patients who had UAPA with a patent ductus arteriosus (PDA). Of the 92 patients with UAPA identified, 78 had isolated UAPA (14 with PDA). Hemoptysis and collateral arteries were observed in 0 and 13% of patients with isolated UAPA who were younger than 1 year, as compared with 24 and 50% of those 20 years of age or older, respectively. Pulmonary hypertension was present in 5% of the patients aged 1 to 19 years. Among patients 20 years or older, however, 32% had pulmonary hypertension, and 8% died. Compared with isolated UAPA, UAPA with PDA was associated with an earlier diagnosis (median age, 20 vs. 0 years; p = 0.002), a higher prevalence of pulmonary hypertension (22% vs. 86%; p < 0.0001), and a higher mortality rate (4% vs. 21%; p = 0.046). Collateral artery formation and pulmonary hypertension progress with age in patients with UAPA. Early diagnosis and revascularization may prevent the age-related progression of UAPA.
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Cardiopatias Congênitas/epidemiologia , Artéria Pulmonar/anormalidades , Adolescente , Fatores Etários , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
CONTEXT: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. Classic (CLCAH) and nonclassic (NCLCAH) forms were reported as total and partial deficiencies, respectively, of adrenal and gonadal steroid hormones. The rarity of LCAH has precluded large-scale epidemiological and clinical investigations. OBJECTIVE: To determine the epidemiological and clinical characteristics of 2 forms of LCAH. DESIGN: A multicenter cross-sectional cohort study in Japan on December 1, 2017. PARTICIPANTS: Fifty-seven patients with LCAH (median age, 23.7 years; range, 0.0-47.5 years). MAIN OUTCOME MEASURES: Patient demographics, STAR genotype, Quigley grade, endocrinological and imaging data, treatment, and prognosis. RESULTS: Fifty-three and 4 patients fulfilled definite and probable diagnostic criteria for LCAH, respectively. When NCLCAH was defined as either Quigley grade 1 in XY karyotype, no episode of salt losing or requirement of fludrocortisone, or onset of primary adrenal insufficiency (PAI) at 1 year or older, patients were divided into groups of 43 patients with CLCAH (75.4%), 11 with NCLCAH (19.3%), and 3 with unclassified LCAH (5.3%). All of the patients with CLCAH and 7/11 NCLCAH (63.6%) were treated with fludrocortisone. CLCAH was diagnosed at a significantly younger age than NCLCAH (median, 0.0 vs 4.0 years). STAR-Arg272Cys or -Met225Thr was identified only in NCLCAH (8/11, 72.7%). CONCLUSIONS: We demonstrated the relative proportions and clinical and molecular characteristics of NCLCAH and CLCAH in Japan. These criteria for NCLCAH correspond to all previously published cases and our cases whose masculinization of the external genitalia, ability of mineralocorticoid production, and onset of PAI were described.
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Hiperplasia Suprarrenal Congênita/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Fludrocortisona/uso terapêutico , Mineralocorticoides/uso terapêutico , Mutação , Fenótipo , Fosfoproteínas/genética , Adolescente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/genética , Adulto , Criança , Pré-Escolar , Estudos Transversais , Transtorno 46,XY do Desenvolvimento Sexual/tratamento farmacológico , Transtorno 46,XY do Desenvolvimento Sexual/genética , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
INTRODUCTION: Gitelman syndrome (GS) is a tubulopathy exhibited by salt loss. GS cases are most often diagnosed by chance blood test. Aside from that, some cases are also diagnosed from tetanic symptoms associated with hypokalemia and/or hypomagnesemia or short stature. As for complications, thyroid dysfunction and short stature are known, but the incidence rates for these complications have not yet been elucidated. In addition, no genotype-phenotype correlation has been identified in GS. METHODS: We examined the clinical characteristics and genotype-phenotype correlation in genetically proven GS cases with homozygous or compound heterozygous variants in SLC12A3 (n = 185). RESULTS: In our cohort, diagnostic opportunities were by chance blood tests (54.7%), tetany (32.6%), or short stature (7.2%). Regarding complications, 16.3% had short stature, 13.7% had experienced febrile convulsion, 4.3% had thyroid dysfunction, and 2.5% were diagnosed with epilepsy. In one case, QT prolongation was detected. Among 29 cases with short stature, 10 were diagnosed with growth hormone (GH) deficiency and GH replacement therapy started. Interestingly, there was a strong correlation in serum magnesium levels between cases with p.Arg642Cys and/or p.Leu858His and cases without these variants, which are mutational hotspots in the Japanese population (1.76 mg/dl vs. 1.43 mg/dl, P < 0.001). CONCLUSION: This study has revealed, for the first time, clinical characteristics in genetically proven GS cases in the Japanese population, including prevalence of complications. Patients with hypokalemia detected by chance blood test should have gene tests performed. Patients with GS need attention for developing extrarenal complications, such as short stature, febrile convulsion, thyroid dysfunction, epilepsy, or QT prolongation. It was also revealed for the first time that hypomagnesemia was not severe in some variants in SLC12A3.
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Deficiência de Vitamina D/complicações , Adulto , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/imunologia , Feminino , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Gravidez , Complicações na Gravidez/imunologia , Síndrome de Sjogren/imunologiaRESUMO
Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.
Assuntos
Insuficiência Adrenal/genética , Cromossomos Humanos Par 7/genética , Transtornos do Crescimento/genética , Mutação/genética , Síndromes Mielodisplásicas/genética , Proteínas/genética , Adolescente , Insuficiência Adrenal/patologia , Criança , Endossomos/metabolismo , Receptores ErbB/genética , Feminino , Genótipo , Transtornos do Crescimento/patologia , Humanos , Hipoadrenocorticismo Familiar , Lactente , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Linhagem , FenótipoRESUMO
The objective of this study was to investigate the growth pattern of children with the salt-wasting form of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (21-OHD). We reviewed the medical records of 13 patients in whom salt-wasting 21-OHD was diagnosed during the first 2 mo of life at our hospital from 1980 through 2008. Six reached adult height. Growth patterns, bone age, biochemical data, and the hydrocortisone dose at each growth stage were analyzed retrospectively. The mean adult height was 155.1 ± 6.5 cm (mean ± SD) in females and 158.1 ± 7.1 cm in males. Although length at birth was normal or longer than the national mean in almost all patients, the mean height SD score of both boys and girls decreased to below 0 SD during infancy. Subsequently, both boys and girls transiently showed growth acceleration and reached their peak growth velocity at 3-10 yr of age. In conclusion, in addition to suppression of growth during infancy, there was inappropriate growth acceleration during childhood. Especially from 3 mo to 3 yr of age, decreasing the hydrocortisone dose in patients who exhibit slower growth may lead to satisfactory height outcomes. Also, strict adjustment of the hydrocortisone dose to avoid accelerated growth from childhood to adolescence might improve adult height outcomes of patients with 21-OHD.
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X-linked myotubular myopathy is a severe congenital myopathy that can involve multiple organs. We report on a 10-month-old boy who manifested X-linked myotubular myopathy with subdural hemorrhage. The diagnosis of X-linked myotubular myopathy was based on typical muscle pathology and MTM1 missense mutation. The patient had undergone no traumatic episodes or bleeding diathesis. Axial growth acceleration is known to occur in X-linked myotubular myopathy, potentially leading to dolichocephaly. In our patient, an enlarged subdural space apparently stretched the bridging veins, increasing susceptibility to subdural hemorrhage. Patients who manifest X-linked myotubular myopathy with typical dolichocephaly are at increased risk for subdural hemorrhage.
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Hematoma Subdural/complicações , Miopatias Congênitas Estruturais/complicações , Causalidade , Hematoma Subdural/diagnóstico por imagem , Humanos , Lactente , Masculino , Miopatias Congênitas Estruturais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
This report concerns control of adrenocortical carcinoma in a 4-yr-old boy by adjuvant mitotane therapy. He presented precocious puberty and was diagnosed with adrenocortical carcinoma. He underwent surgical resection, and adjuvant mitotane therapy was initiated, leading to a final dose of 5.0 g/day. Despite monitoring of the plasma mitotane level, encephalopathy developed 5 mo after initiation. Although he recovered from the encephalopathy, careful follow-up of his growth and development is necessary. On the other hand, he has been free of recurrence and metastases for 3 yr since discontinuation of mitotane. A high dose of mitotane is potentially effective as an adjuvant chemotherapy for adrenocortical carcinoma, although optimal and safe usage needs to be established for children.
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Interaction between Programmed cell death-1 (PD-1), a member of costimulatory molecules, and its receptors Programmed cell Death-1 Ligand 1 (PD-L1) and Programmed cell Death-1 Ligand 2 (PD-L2), play an important role in the negative regulation of immune reactions. It was shown that a polymorphism in a regulatory site of the PD-1 gene was associated with susceptibility to several autoimmune diseases in various ethnic groups, whereas the contribution of the PD-1 gene or its ligand genes to the onset of type 1 diabetes (T1D) mellitus in the Japanese population remains unknown. We first screened PD-1, PD-L1, and PD-L2 genes for polymorphisms in the Japanese population, and then investigated the frequencies of polymorphisms in patients with T1D mellitus in comparison with healthy controls. In total, we identified 26 polymorphic sites within these genes, and then 23 polymorphisms with minor allele frequencies greater than 5% were intensively analyzed for genotyping in the patients and the controls. As a result, allele and genotype frequencies of the polymorphism numbers 2, 3, 4, 5, 6, and 8 in the PD-1 gene were different to some extent between the patients and the controls with P < 0.05, which did not reach statistical significance after the correction of multiple comparisons. Allele or genotype frequencies of any SNPs in the PD-L1 or PD-L2 gene did not show differences between the patients and the controls. The frequencies of the estimated haplotypes, those of which consisted of polymorphism numbers 2, 3, 4, 5, 6, and 8 in the PD-1, were significantly different between the patients and the controls (P = 0.00095). The in vitro assessment for a transcription activity of each haplotype of the PD-1 gene by luciferase assay did not demonstrate a functional difference between the haplotypes. In conclusion, the genetic evaluation by association study demonstrated that the PD-1 gene was a predisposing gene to the development of T1D mellitus in the Japanese population.
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Antígenos CD/genética , Proteínas Reguladoras de Apoptose/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Haplótipos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Ligantes , Masculino , Polimorfismo Genético , Receptor de Morte Celular Programada 1RESUMO
The identification of molecular determinants involved in the promotion of metastasis and development of androgen insensitive prostate cancer (AI-PCa) is necessary to discriminate aggressive from indolent disease and to identify therapeutic targets for advanced disease. Overexpression of one particular member of the insulin like growth factor (IGF) axis, IGFBP-2, is implicated in the development of AI-PCa and other cancers. Using the LNCaP human PCa progression model, we show that the AI and metastatic prostate cancer cell line C4-2B4 expresses greater amounts of secreted IGFBP-2 than the androgen sensitive (AS), non-metastatic LNCaP progenitor cell line. Further, the ability of androgens to decrease extracellular IGFBP-2 levels is attenuated in the AI and metastatic C4-2 cell line. The ability of androgen to negatively regulate extracellular IGFBP-2 levels was blocked by Casodex in a dose-dependent manner. The mechanism underlying the androgen-induced downregulation of secreted IGFBP-2 appears to involve extracellular proteolysis, resulting in the production of IGFBP-2 fragments lacking the ability to bind IGF-I and IGF-II. As C4-2 cells have an attenuated ability to proteolyze IGFBP-2 in response to androgen and C4-2B4 cells express greater amounts of IGFBP-2, our data implies that the diminished regulation of IGFBP-2 and loss of associated proteolytic fragments play a role in the increased metastatic behavior of these cells in vivo. Furthermore, our results suggest that either increased levels of intact IGFBP-2 or decreased levels of IGFBP-2 proteolytic fragments could serve as a biomarker to monitor for progression to AI-PCa.
Assuntos
Androgênios/farmacologia , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Endopeptidases/metabolismo , Humanos , Masculino , Neoplasias da Próstata/secundário , Receptores Androgênicos/metabolismoRESUMO
BACKGROUND: Nutritional rickets is considered rare in developed countries. However, reports on vitamin D deficiency rickets caused by improper lifestyle have recently increased. The clinical and laboratory characteristics of patients with vitamin D deficiency rickets treated at Fukuoka Children's Hospital, Fukuoka, Japan, were evaluated to clarify current causes and ways to prevent this disease. METHODS: Clinical records were reviewed, and obtained information and data were summarized. RESULTS: Eight patients with vitamin D deficiency rickets (five boys and three girls) were treated during the past 10 years (January 1992 to December 2001). Two infants were referred to the hospital for hypocalcemia and convulsion, and six toddlers (1-2 years old) for bowlegs. One patient lacked exposure to sunlight, and six had an unbalanced diet. The cause of rickets could not be established in one patient. Anthropometric and laboratory data did not indicate malnutrition. Serum alkaline phosphatase was 2518.3 +/- 1401.7 IU/l, calcium was 8.2 +/- 2.6 mg/dL (including 4.7 mg/dL in one infant and 4.8 mg/dL in another), and phosphorus was 4.9 +/- 1.0 mg/dL. High sensitive parathyroid hormone was 1393.1 +/- 321.7 pg/mL (reference range, 180-560), 1,25-dihydroxyvitamin D was 86.0 +/- 61.5 pg/mL (reference range, 20-70), and 25-hydroxyvitamin D was 11.6 +/- 5.6 ng/mL (reference range, 10-30). The patients recovered with a change to a balanced diet, the promotion of weaning, and/or an increase in sunlight exposure. CONCLUSION: Vitamin D deficiency rickets remains a common condition that is best managed by education and disease prevention.
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Estilo de Vida , Raquitismo/etiologia , Vitamina D/análogos & derivados , Fosfatase Alcalina/sangue , Osso e Ossos/metabolismo , Pré-Escolar , Feminino , Homeostase , Humanos , Lactente , Japão/epidemiologia , Masculino , Hormônio Paratireóideo/sangue , Raquitismo/epidemiologia , Luz Solar , Vitamina D/sangueRESUMO
BACKGROUND: Intensive insulin therapy increases the frequency of severe hypoglycemia despite markedly improved glycemic control in patients with type 1 diabetes mellitus. To determine the optimal dose of insulin, the authors designed algorithms based on self-monitored blood glucose levels. METHODS: Each dose of insulin was composed of two components: a basal dose determined on the basis of blood glucose levels over the previous two days and an additional dose determined on the basis of blood glucose level just before insulin injection. The patients were instructed to adjust each dose according to the algorithms. The authors investigated the effects of using algorithms on glycemic control, anthropometric data, body composition, and lipid profile in seven females with type 1 diabetes 12-20 years old. RESULTS: After 3 months, the daily dose of insulin increased significantly from 0.93 +/- 0.18 to 1.16 +/- 0.26 units/kg of body weight, and haemoglobin A(1C) decreased significantly from 8.27 +/- 1.33 to 6.50 +/- 0.64%. Severe hypoglycemia, however, did not occur. Body mass index increased significantly from 21.7 +/- 2.7 to 22.7 +/- 2.9 kg/m(2) with no increase in the percentage of body fat. All lipid-profile data showed a decreasing trend. CONCLUSIONS: Algorithms developed on the basis of self-monitored blood glucose levels are useful in determining the optimal dose of insulin and can improve glycemic control and lipid metabolism.
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Algoritmos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Análise de Variância , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/diagnóstico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Satisfação do Paciente , Probabilidade , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
We report a rare case of growth hormone and gonadotropin deficiency associated with dysmorphic features. A 16-year-old boy had left anophthalmia, microphallus, bilateral cryptorchidism, and mental retardation. His chromosomal karyotype was normal, 46, XY. Endocrinological studies revealed growth hormone and gonadotropin deficiency, attributed to hypothalamic dysfunction. Magnetic resonance imaging scan of the head showed a hypoplastic pituitary gland, decreased high intensity signals in the pituitary posterior lobe, absence of the left eye, and a hypoplastic left optic nerve with no abnormality of the pituitary stalk, corpus callosum, or septum pellucidum. Although not completely consistent with the features of septo-optic dysplasia (SOD), his condition was considered within the spectrum of SOD. Despite similarities to the Hesx1 knockout mouse, a model of human SOD, mutation analyses revealed no mutations or polymorphisms in coding regions of any exons or intron-exon boundaries of the HESX1 gene. Further genetic studies of this patient may improve understanding of molecular mechanisms involved in pituitary development.