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1.
J Bone Miner Metab ; 39(6): 1066-1075, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34255195

RESUMO

INTRODUCTION: Measurement of fibroblast growth factor 23 (FGF23) has been reported to be clinically useful for the differential diagnosis of chronic hypophosphatemia. However, assays for research use only are available in Japan. Thus, the objective of this study was to examine the clinical utility of a novel and automated chemiluminescent enzyme immunoassay for the measurement of FGF23. MATERIALS AND METHODS: Participants were recruited from July 2015 to January 2017 at six facilities in Japan. Thirty-eight patients with X-linked hypophosphatemic rickets (XLH 15 males, 23 females, age 0-66 years), five patients with tumour-induced osteomalacia (TIO 3 males, 2 females, age 60-73 years), and twenty-two patients with hypophosphatemia (11 males, 11 females, age 1-75 years) caused due to other factors participated in this study. RESULTS: With the clinical cut-off value of FGF23 at 30.0 pg/mL indicated in the Diagnostic Guideline of Rickets/Osteomalacia in Japan, the sensitivity and specificity of FGF23-related hypophosphatemic rickets/osteomalacia without vitamin D deficiency (disease group-1) were 100% and 81.8%, respectively, which distinguished it from non-FGF23-related hypophosphatemia (disease group-2). Furthermore, the diagnostic sensitivity of FGF23-related hypophosphatemia with vitamin D deficiency remained at 100%. Among the four patients with FGF23 levels ≥ 30.0 pg/mL in disease group-2, two patients with relatively higher FGF23 values were suspected to have genuine FGF23-related hypophosphatemia, due to the ectopic production of FGF23 in pulmonary and prostate small cell carcinomas. CONCLUSION: The novel FGF23 assay tested in this study is useful for the differential diagnosis of hypophosphatemic rickets/osteomalacia in a clinical setting.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Osteomalacia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Mol Genet Metab ; 125(1-2): 174-180, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30049651

RESUMO

OBJECTIVE: To investigate the utility of serum pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. METHODS: Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. RESULTS: Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. CONCLUSIONS: The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.


Assuntos
Fosfatase Alcalina/genética , Terapia de Reposição de Enzimas , Hipofosfatasia/tratamento farmacológico , Imunoglobulina G/genética , Fosfato de Piridoxal/sangue , Proteínas Recombinantes de Fusão/genética , Adolescente , Adulto , Fosfatase Alcalina/sangue , Fosfatase Alcalina/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Etanolaminas/urina , Feminino , Humanos , Hipofosfatasia/sangue , Hipofosfatasia/patologia , Hipofosfatasia/urina , Imunoglobulina G/uso terapêutico , Lactente , Recém-Nascido , Masculino , Piridoxal/sangue , Ácido Piridóxico/sangue , Proteínas Recombinantes de Fusão/uso terapêutico , Vitamina B 6/metabolismo , Adulto Jovem
3.
Endocr J ; 65(6): 593-599, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29526992

RESUMO

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.


Assuntos
Hipocalcemia/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Hipocalcemia/sangue , Hipocalcemia/diagnóstico , Incidência , Lactente , Japão/epidemiologia , Masculino , Prevalência , Raquitismo/sangue , Raquitismo/diagnóstico , Raquitismo/epidemiologia , Avaliação de Sintomas , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
4.
Clin Calcium ; 28(10): 1343-1349, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30269116

RESUMO

Vitamin D dependency is caused by inborn error in the process of vitamin D metabolism or action. It is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)2D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)2D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate diagnosis and therapy.


Assuntos
Raquitismo Hipofosfatêmico Familiar/etiologia , Deficiência de Vitamina D/complicações , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Humanos , Osteomalacia , Vitamina D , Deficiência de Vitamina D/diagnóstico , Vitaminas
5.
Pediatr Nephrol ; 32(10): 1845-1850, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27450397

RESUMO

Nail-patella syndrome (NPS) is an autosomal-dominant disease caused by LMX1B mutations and is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Renal involvement is the major determinant of the prognosis for NPS. Patients often present with varying degrees of proteinuria or hematuria, and can occasionally progress to chronic renal failure. Recent genetic analysis has found that some mutations in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy). The classic term "nail-patella syndrome" would not represent disease conditions in these cases. This review provides an overview of NPS, and highlights the molecular genetics of NPS nephropathy and LMX1B-associated nephropathy. Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed. This recent progress provides insights that help to define potential targeted therapeutic strategies for LMX1B-associated diseases.


Assuntos
Redes Reguladoras de Genes/genética , Nefropatias/genética , Proteínas com Homeodomínio LIM/genética , Síndrome da Unha-Patela/genética , Fatores de Transcrição/genética , Animais , Análise Mutacional de DNA , Modelos Animais de Doenças , Membrana Basal Glomerular/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Terapia de Alvo Molecular/métodos , Mutação , Síndrome da Unha-Patela/diagnóstico , Síndrome da Unha-Patela/tratamento farmacológico
6.
BMC Nephrol ; 18(1): 100, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28335748

RESUMO

BACKGROUND: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by mutations in the LMX1B gene and is characterized by nail dysplasia, skeletal abnormalities, and nephropathy. We herein report a case of steroid-resistant nephrotic syndrome (SRNS) prior to overt orthopedic symptoms in a patient with NPS. CASE PRESENTATION: A 24-year-old woman presented to our hospital with knee pain. She had poorly developed nails, hypoplastic patellas, dislocation of the elbows, and iliac horns in the pelvis. At the age of 7, she developed nephrotic syndrome and was diagnosed with primary focal segmental glomerulosclerosis by renal biopsy. She received long-term corticosteroid therapy with no obvious response. Her clinical course and orthopedic manifestations indicated NPS, and a genetic analysis showed a de novo mutation in the LMX1B gene (c.819 + 1G > A). Nephropathy in this case was considered to be associated with NPS. Therefore, we discontinued corticosteroids without the exacerbation of nephrotic syndrome. CONCLUSIONS: Patients with NPS may develop nephrotic syndrome prior to overt orthopedic symptoms and only show non-specific findings in renal biopsy at an early stage of NPS nephropathy. Hereditary nephrotic syndrome, often presenting as childhood-onset SRNS, may also be difficult to diagnose in patients with the following conditions: renal symptoms prior to overt extrarenal symptoms, de novo mutations, and non-specific findings in renal biopsy. Therefore, in the management of SRNS in children, we need to reconsider the possibility of hereditary diseases such as NPS even without a family history.


Assuntos
Proteínas com Homeodomínio LIM/genética , Síndrome da Unha-Patela/diagnóstico , Síndrome Nefrótica/diagnóstico , Fatores de Transcrição/genética , Corticosteroides/uso terapêutico , Feminino , Humanos , Rim/patologia , Rim/ultraestrutura , Mutação , Síndrome da Unha-Patela/complicações , Síndrome da Unha-Patela/genética , Síndrome da Unha-Patela/patologia , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/genética , Falha de Tratamento , Adulto Jovem
7.
Pediatr Int ; 59(1): 99-102, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28102624

RESUMO

Partial monosomy of 10p is a rare chromosomal abnormality. Common features are hypoparathyroidism, deafness, renal anomalies, distinctive facies, and mental retardation, with phenotypic variability. We report two patients with chromosomal abnormalities identified on single-nucleotide polymorphism (SNP) array analysis. Although patient 1 had common features of monosomy10p, G-banding indicated a normal karyotype. SNP array and fluorescence in situ hybridization (FISH), however, indicated unbalanced translocation of a 10p terminal deletion of 11.7 Mb and a 15q terminal duplication of 8.2 Mb. In patient 2, SNP array and FISH indicated a 10p terminal deletion of 12.6 Mb and a 7q terminal duplication of 1.9 Mb. This is the first case report of monosomy 10p combined with trisomy 15q (patient 1). Because the clinical heterogeneity of the 10p deletion syndrome would be affected by duplication of another chromosome, we emphasize that SNP/microarray analysis is necessary to confirm genotype-phenotype correlation.


Assuntos
Anormalidades Múltiplas/genética , Transtornos Cromossômicos/genética , Polimorfismo de Nucleotídeo Único , Trissomia/genética , Adulto , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 15/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Translocação Genética
8.
Clin Calcium ; 26(2): 277-83, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-26813508

RESUMO

Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2.


Assuntos
Raquitismo Hipofosfatêmico Familiar , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Calcitriol , Cálcio/administração & dosagem , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/etiologia , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/terapia , Humanos , Mutação , Patologia Molecular , Receptores de Calcitriol/genética , Vitamina D/administração & dosagem
9.
Pediatr Int ; 57(5): 864-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25865080

RESUMO

BACKGROUND: Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease (metabolic bone disease of prematurity, MBDP). MBDP is frequently found in very low-birthweight (VLBW) infants, but long-term height prognosis is not well known. METHODS: VLBW infants from two major neonatal intensive care units were studied. Medical records were reviewed. A total of 143 subjects were analyzed after excluding subjects who died, or who had severe complications that could affect linear growth, Silver-Russell syndrome, severe cholestasis, and/or chromosomal abnormality. The relationship between MBDP and height at age 3 was investigated. RESULTS: Height standard deviation score (SDS) at age 3 negatively correlated with peak serum alkaline phosphatase (ALP) activity in early life (r = -0.30, P = 0.0003) and positively correlated with serum phosphorus (P) at peak ALP (r = 0.33, P = 0.0002). In addition, serum P independently affected height SDS at 3 years of age (ß = 0.19, P = 0.018), and was significantly different between infants with and without catch-up growth in height (difference: 0.23 mmol/L, 95%CI: 0.09-0.36, P = 0.0010). CONCLUSIONS: MBDP, particularly hypophosphatemia in the early period of life, is associated with linear growth until 3 years of age in VLBW infants.


Assuntos
Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/metabolismo , Osso e Ossos/metabolismo , Doenças do Prematuro/epidemiologia , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Minerais/metabolismo , Doenças Ósseas Metabólicas/diagnóstico , Pré-Escolar , Progressão da Doença , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/metabolismo , Masculino , Prognóstico
10.
Matern Child Nutr ; 11(4): 525-36, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24118748

RESUMO

Maternal vitamin D status is important for fetal development and the prevention of pregnancy complications. Mothers require both sufficient intakes and skin production of this vitamin. We investigated the validity and test-retest reliability of a self-administered diet history questionnaire (DHQ) to establish a method of assessing vitamin D intakes of Japanese pregnant women, using a serum marker. A total of 245 healthy pregnant women in the second trimester, who were not taking vitamin D supplements, were recruited at a university hospital in Tokyo between June 2010 and July 2011. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured as an indicator of vitamin D status. To assess the test-retest reliability of the DHQ, 58 pregnant women completed it twice within a 4-5-week interval. Significant positive correlations between intakes and serum concentrations of vitamin D were found (r = 0.266 for daily intakes and r = 0.249 for energy-adjusted intakes). In the winter investigation in which the serum 25(OH)D concentrations were less likely to be affected by sunlight exposure, the correlation coefficients were 0.304 for both daily and energy-adjusted intakes. After excluding participants with pregnancy-associated nausea, the coefficients increased. The intraclass correlation coefficient between vitamin D intakes estimated from the two-time DHQ was 0.638. The DHQ provides an acceptable validity and reliability of the vitamin D intake of Japanese pregnant women. However, the data of women with nausea should be interpreted with caution. We believe that the DHQ is a useful questionnaire to grasp and improve vitamin D intakes during pregnancy.


Assuntos
Registros de Dieta , Inquéritos e Questionários/normas , Vitamina D/administração & dosagem , Adulto , Feminino , Humanos , Japão , Avaliação Nutricional , Gravidez , Segundo Trimestre da Gravidez , Reprodutibilidade dos Testes , Vitamina D/análogos & derivados , Vitamina D/sangue
11.
Nihon Rinsho ; 73(11): 1959-64, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26619675

RESUMO

Kenny-Caffey syndrome (KCS) is a very rare dysmorphologic syndrome characterized by proportionate short stature, cortical thickening and medullary stenosis of tubular bones, delayed closure of anterior fontanelle, eye abnormalities, and hypoparathyroidism. Two types of KCS were known: the autosomal recessive form (KCS type 1), which is caused by mutations of the TBCE gene, and the autosomal dominant form (KCS type 2), which is caused by mutations of the FAM111A gene. TBCE mutation also causes hypoparathyroidism-retardation-dysmorphism syndrome, and FAM111A mutation also causes gracile bone dysplasia. These two diseases can be called as KCS-related syndromes. In this article, we review the clinical manifestations of KCS and discuss its related syndromes.


Assuntos
Nanismo , Hiperostose Cortical Congênita , Hipocalcemia , Anormalidades Múltiplas , Calcinose , Nanismo/genética , Nanismo/patologia , Transtornos do Crescimento , Humanos , Hiperostose Cortical Congênita/genética , Hiperostose Cortical Congênita/patologia , Hipocalcemia/genética , Hipocalcemia/patologia , Hipoparatireoidismo , Deficiência Intelectual , Chaperonas Moleculares/genética , Osteocondrodisplasias , Receptores Virais/genética , Convulsões
12.
Nephrol Dial Transplant ; 29(1): 81-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24042019

RESUMO

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal-dominant disorder caused by LMX1B mutation. In patients with the renal lesions typical of NPS without skeletal or nail findings, it is described as nail-patella-like renal disease (NPLRD). However, the pathogenesis of NPLRD is largely unknown. METHODS: A 6-year-old girl with microscopic haematuria and mild proteinuria was diagnosed with NPLRD because of an aberrantly thickened glomerular basement membrane (GBM) and deposition of Type III collagen in the GBM observed by electron microscopy. Immunohistological analyses of podocyte protein expression were performed on biopsy tissues. Sequence analysis of LMX1B was performed, and the functional consequences of the detected mutation were analysed by luciferase reporter assay. RESULTS: When analysing molecules that are important for podocyte development, maintenance and maturation, CD2AP expression was found to be altered in the podocytes. A novel LMX1B missense mutation (R246Q) was identified. Functional analyses revealed partial but significant impairment of R246Q transcriptional activity. However, no dominant-negative effect of R246Q was detected, which suggests that NPLRD is caused by LMX1B haploinsufficiency. CONCLUSIONS: This is the first report on LMX1B mutation identified in a patient with NPLRD. Residual transcriptional activity would account for normality of the nails and patella in this case. Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.


Assuntos
Proteínas com Homeodomínio LIM/genética , Mutação de Sentido Incorreto/genética , Síndrome da Unha-Patela/genética , Nefrite Hereditária/genética , Fatores de Transcrição/genética , Animais , Criança , Feminino , Humanos , Imuno-Histoquímica , Rim/patologia , Síndrome da Unha-Patela/patologia , Nefrite Hereditária/patologia , Podócitos/metabolismo
14.
Horm Res Paediatr ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493780

RESUMO

INTRODUCTION: Autosomal dominant hypophosphatemic rickets (ADHR) is caused by pathogenic variants in the fibroblast growth factor 23 (FGF23) gene, which plays a key role in the regulation of phosphorus metabolism. FGF23 has the RXXR motif recognized by furin, leading to cleavage between R179 and S180 and thereby inactivating the protein's function. Previously reported variants in FGF23 causing ADHR occurred only affecting residues R176 or R179, which are located in the RXXR motif, leading to impaired cleavage. Impairment of protein cleavage increases bioactive FGF23 levels, subsequently resulting in the development of ADHR. CASE PRESENTATION: A 13-year-old boy with ADHR with the appearance of rickets on bone radiographs as well as documented hypophosphatemia was found to have a novel S180I variant in the FGF23 gene. Unlike previously reported pathogenic variants, this novel variant was located outside the RXXR motif. Subsequently, western blotting showed that the S180I mutant was resistant to proteolysis than the wild-type, similar to pathogenic variants model mutant (R176Q/R179Q). CONCLUSION: The novel variant in FGF23 presented herein, found in a patient with ADHR, is the first pathogenic variant found outside the typical furin recognition sequence. It exhibits proteolysis resistance due to impaired cleavage.

15.
Am J Med Genet A ; 161A(9): 2234-43, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23913813

RESUMO

Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty-five MLL2 mutations and two KDM6A mutations were novel. Non-protein truncating-type MLL2 mutations were mainly located around functional domains, while truncating-type mutations were scattered through the entire coding region. The facial features of patients in the MLL2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Face/anormalidades , Doenças Hematológicas/genética , Histona Desmetilases/genética , Mutação , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Doenças Vestibulares/genética , Anormalidades Múltiplas/diagnóstico , Adolescente , Adulto , Substituição de Aminoácidos , Criança , Pré-Escolar , Exoma , Fácies , Feminino , Estudos de Associação Genética , Doenças Hematológicas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Taxa de Mutação , Fenótipo , Doenças Vestibulares/diagnóstico , Inativação do Cromossomo X , Adulto Jovem
16.
BMC Infect Dis ; 13: 465, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-24093148

RESUMO

BACKGROUND: Parvovirus B19 can cause petechial rashes in the acute phase of illness as well as erythema infectiosum (fifth disease) during convalescence. This petechial rash is often called "gloves and socks" syndrome because of the typical distribution of the eruption. However, involvement of other sites (e.g., intertriginous area) and generalized involvement have been recently recognized. We report here a patient with parvovirus-associated petechiae and cephalhematoma. CASE PRESENTATION: The patient was a previously healthy 10-year-old boy. There was a family history of fatal bleeding; his sister died of intracranial bleeding with an uncertain cause at the age of 5 months. The patient was admitted to our hospital because of sudden onset of cephalhematoma associated with fever. He reported that he had no recent head trauma but that he massaged his scalp on the day before admission. On admission, his temperature was 38.8°C; otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes were present on his trunk and limbs. The initial laboratory tests were essentially normal, including platelet count and coagulation tests. Expanded laboratory tests were repeated to explore the etiology of his skin hemorrhage, all of which indicated that hematological disorders were unlikely. His symptoms subsided spontaneously over the next few days and he was discharged uneventfully. Anti-parvovirus IgM titer was elevated during hospitalization and typical erythema infectiosum was seen approximately 1 week after discharge. During 6 months follow-up, he remained stable without recurrence of a hemorrhagic episode. Finally, we concluded that his cephalhematoma was responsible for acute parvoviral infection. CONCLUSIONS: This is believed to be the first report describing a possible association between parvovirus B19 infection and cephalhematoma. Parvovirus B19 infection should be considered in the differential diagnosis of children who present with unexplained hemorrhage such as cephalhematoma or petechiae.


Assuntos
Exantema/virologia , Hemorragia/virologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Púrpura/virologia , Criança , Humanos , Masculino , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/fisiologia
17.
Clin Calcium ; 23(10): 1437-43, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24076641

RESUMO

Vitamin D dependency was first termed for patients resembling vitamin D-deficiency but require high doses of vitamin D administration. Now this disease is known to be caused by defective conversion of 25OHD to 1,25 (OH) 2D, which is termed vitamin D-dependent rickets type 1 or 1α-hydroxylase deficiency, or by end-organ unresponsiveness to 1,25 (OH) 2D, which is called vitamin D-dependent rickets type 2 or hereditary vitamin D-resistant rickets. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for some atypical cases for adequate therapy.


Assuntos
Raquitismo/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/metabolismo , Calcitriol/deficiência , Humanos , Mutação/genética , Raquitismo/diagnóstico , Raquitismo/tratamento farmacológico , Raquitismo/genética
18.
Endocr J ; 59(11): 1007-14, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22785457

RESUMO

The prevalence of vitamin D deficiency, presenting as hypocalcemic seizures or rickets in children, is increasing worldwide due to insufficient vitamin D intake and lack of exposure to sunshine. However, considering that relatively few children with low 25-hydroxyvitamin D [25(OH)D] levels manifest symptoms, it is possible that genetic factors may predispose individuals to vitamin D deficiency. Recent twin studies have reported that the level of serum of 25(OH)D is influenced by genetic factors. In addition, genome-wide association studies and candidate gene studies have revealed that several vitamin D-related genes, including VDR, GC, NADSYN1, CYP2R1, CYP24A1, CYP27B1, and C10orf88 contribute to variations in serum 25(OH)D levels. To investigate whether genetic predisposition contributes to vitamin D deficiency, we analyzed polymorphisms in vitamin D-related genes in 30 Japanese patients with vitamin D deficiency presenting at less than 4 years of age, along with 66 controls. A χ(2) test showed that the genotype frequencies of BsmI polymorphism in VDR and rs10898191 in NADSYN1 were significantly different between the two groups. The allele frequencies of BsmI, ApaI, TaqI in VDR, rs10898191 in NADSYN1, and rs705117 in GC were also significantly different. In particular, the frequency of the BAtS haplotype in VDR was significantly increased in the patient group relative to controls (p = 0.0014; odds ratio, 5.61; 95% confidence interval 1.92 - 16.40). Although this is a small study, our findings suggest that VDR, NADSYN1, and GC polymorphisms may be linked to the manifestation of vitamin D deficiency in Japanese children.


Assuntos
Amida Sintases/genética , Receptores de Calcitriol/genética , Deficiência de Vitamina D/genética , Proteína de Ligação a Vitamina D/genética , Vitamina D/genética , Povo Asiático , Aleitamento Materno/efeitos adversos , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
19.
Acta Paediatr ; 101(6): e259-62, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22251140

RESUMO

UNLABELLED: Glucose transporter 1 deficiency syndrome (GLUT1DS) is an autosomal dominant disorder of brain energy metabolism caused by impaired GLUT1-mediated glucose transport across the blood-brain barrier. Although the clinical spectrum of this disorder is expanding rapidly, the growth patterns and endocrine status of these patients are not well known. We report the case of a boy aged 12 years and 7 months who has GLUT1DS complicated by growth failure. His failure to grow had progressed since birth, and his body height was 125 cm (-3.6 SDS). Growth hormone stimulation tests showed severe growth hormone deficiency (GHD), and we initiated GH replacement therapy. After 2 years of treatment, the boy's growth rate recovered from 1.7 cm/year before treatment, to 7.5 cm/year and 4.3 cm/year after treatment with no adverse effects. We speculate that GHD is a possible complication of GLUT1DS and discuss the underlying causative mechanism. CONCLUSION: GHD may be a possible complication of GLUT1DS.


Assuntos
Transtornos do Metabolismo de Glucose/complicações , Transportador de Glucose Tipo 1/deficiência , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/deficiência , Criança , Humanos , Masculino
20.
Horm Res Paediatr ; 94(5-6): 211-218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34425577

RESUMO

BACKGROUND: About twice as many boys as girls undergo growth hormone (GH) therapy in GH deficiency (GHD). However, this sex difference may not correctly reflect a real incidence. OBJECTIVES: We analyzed the evidence of a selection bias whereby more boys seek treatment at short stature clinics. SUBJECTS AND METHODS: The present study included 3,902 children who visited 17 short stature clinics with a height SD score of -2 SD or less. The percentage of children who underwent the GH stimulation test was compared between boys and girls, as was the percentage of children ultimately diagnosed with GHD. RESULTS: The children comprised 2,390 boys (61.3%) and 1,512 girls (38.7%), with a boy:girl ratio of 1.58:1. The percentage of children who underwent the GH stimulation test did not differ between boys (45.7%) and girls (49.8%). Among the children who underwent the GH stimulation test, the percentage diagnosed with GHD did not differ significantly between boys (22.0%) and girls (20.1%). The boy:girl ratio of children diagnosed with GHD was 1.59:1. CONCLUSIONS: The boy:girl ratio of children with short stature (1.58:1) did not differ significantly from that of children diagnosed with GHD (1.59:1). These results indicate that the predominance of boys in GHD does not reflect a real incidence, but rather a selection bias whereby a higher proportion of boys with short stature seek treatment at clinics. This difference arises because parents are more concerned about boys' height, and because boys reach adult height at an older age.


Assuntos
Instituições de Assistência Ambulatorial , Viés , Estatura/fisiologia , Hormônio do Crescimento Humano/deficiência , Criança , Feminino , Humanos , Japão , Masculino , Fatores Sexuais
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