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CONTEXT: Thyroglobulin (Tg), encoded by TG, is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). OBJECTIVE: We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. METHODS: We screened 1061 patients with CH for 13 CH-related genes and identified 30 patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into 2 groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the 7 missense variants using HEK293 cells. RESULTS: Twenty-seven rare TG variants were detected, including 15 nonsense, 3 frameshift, 2 splice-site, and 7 missense variants. Patients were divided into 2 groups: 13 patients with biallelic truncating variants and 17 patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with thyrotropin stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the 7 missense variants was confirmed in vitro. CONCLUSION: To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.
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Hipotiroidismo Congénito , Estudios de Asociación Genética , Tamizaje Neonatal , Tiroglobulina , Humanos , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/diagnóstico , Femenino , Masculino , Tiroglobulina/genética , Recién Nacido , Japón/epidemiología , Preescolar , Mutación Missense , Lactante , Niño , Fenotipo , Genotipo , Células HEK293 , Pueblos del Este de AsiaAsunto(s)
Enfermedad de Hirschsprung , Síndromes de Inmunodeficiencia , Osteocondrodisplasias , Enfermedades de Inmunodeficiencia Primaria , Humanos , Pueblos del Este de Asia , Cabello/anomalías , Enfermedad de Hirschsprung/diagnóstico , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , HermanosRESUMEN
Sitosterolemia (OMIM #210250) is a rare lipid disorder caused by variants in genes encoding adenosine triphosphate (ATP)-binding cassette subfamily G Member 5 (ABCG5) or 8 (ABCG8), which play roles in the intestinal and biliary excretion of cholesterol and plant sterols, such as sitosterol and campesterol. Although considered an autosomal recessive disorder, recent reports have shown that a heterozygous ABCG5 variant can also cause mild symptoms. Here, we report the case of an infant with a heterozygous variant of ABCG5. A 6-mo-old breast-fed Japanese male infant was found to have elevated serum total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels of 528 mg/dL and 449 mg/dL, respectively, upon examination for growth disturbances. As weaning progressed, the cholesterol levels normalized. Genetic analysis revealed that the patient and his mother had the heterozygous variant c.1166G>A (p.Arg389His) in ABCG5. Compared to his father, who did not have the ABCG5 variant, the patient and his mother had mild elevations of serum sitosterol and campesterol. Serum sitosterol and campesterol levels were 9.6 and 12 µg/mL for the patient, 4.9 and 9.3 µg/mL for his mother, and 2.1 and 3.4 µg/mL for his father, respectively. Therefore, heterozygous variants of ABCG5 may lead to transient hypercholesterolemia during breastfeeding.
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SLC26A4 is a known iodide transporter, and is localized at the apical membrane of thyrocytes. Previously, we reported that SLC26A7 is also involved in iodide transport and that Slc26a7 is a novel causative gene for congenital hypothyroidism. However, its detailed role in vivo remains to be elucidated. We generated mice that were deficient in Slc26a7 and Slc26a4 to delineate differences and associations in their roles in iodide transport. Slc26a7-/- mice showed goitrous congenital hypothyroidism and mild growth failure on a normal diet. Slc26a7-/- mice with a low iodine environment showed marked growth failure. In contrast, Slc26a4-/- mice showed no growth failure and hypothyroidism in the same low iodine environment. Double-deficient mice showed more severe growth failure than Slc26a7-/- mice. RNA-seq analysis revealed that the number of differentially expressed genes (DEGs) in Slc26a7-/- mice was significantly higher than that in Slc26a4-/- mice. These indicate that SLC26A7 is more strongly involved in iodide transport and the maintenance of thyroid function than SLC26A4.
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Antiportadores de Cloruro-Bicarbonato/metabolismo , Hipotiroidismo Congénito , Yodo , Transportadores de Sulfato/metabolismo , Animales , Antiportadores de Cloruro-Bicarbonato/genética , Hipotiroidismo Congénito/genética , Yoduros , Yodo/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Ratones , Transportadores de Sulfato/genéticaRESUMEN
X-linked nephrogenic diabetes insipidus (NDI) is caused by variations in arginine vasopressin receptor 2 (AVPR2). Some patients show partial resistance to arginine vasopressin (AVP). A 19-month-old Japanese boy presented with polydipsia since infancy. His mother had a history of polydipsia during pregnancy, and his maternal granduncle also had polydipsia. Intermediate urine osmolality and markedly high plasma AVP levels were observed in the water deprivation test. Subsequent pitressin administration caused no further elevation in urine osmolality. We diagnosed the patient with partial NDI, initiated therapy with hydrochlorothiazide, and placed him on a low-sodium diet. Although his urine volume decreased by 20-30% after the initiation of therapy, progressive hydronephrosis and growth retardation developed 2 years later. We investigated his genetic background by multiplex targeted sequencing of genes associated with inherited renal diseases, including AVPR2 and aquaporin-2 (AQP2). We identified a hemizygous missense variant in AVPR2 NM_000054:c.371A>G,p.(Tyr124Cys) in the boy and a heterozygous variant in the mother at the same locus. Distinguishing partial NDI from primary polydipsia is difficult because of its mild symptoms. Markedly elevated plasma AVP levels with intermediate urine osmolality may suggest partial NDI, and genetic analysis can be useful for such patients.
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Here, we present a previously healthy adolescent with aseptic meningitis without skin rash caused by varicella vaccine derived from the Oka/Biken strain; the patient received a single dose of varicella vaccine at 1 year of age. Pediatricians should be aware of the potential for reactivation of varicella vaccine derived from the Oka/Biken strain, which can cause aseptic meningitis in vaccinated children even in the absence of a skin rash.
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Vacuna contra la Varicela/efectos adversos , Varicela/prevención & control , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/etiología , Adolescente , Vacuna contra la Varicela/administración & dosificación , Exantema , Femenino , Voluntarios Sanos , Humanos , Infección Latente , Vacunación/efectos adversos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversosRESUMEN
Background: Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transmembrane transporter protein. MCT8 deficiency induces severe X-linked psychomotor retardation. Previous reports have documented delayed myelination in the central white matter (WM) in these patients; however, the regional pattern of myelination has not been fully elucidated. Here, we describe the regional evaluation of myelination in four patients with MCT8 deficiency. We also reviewed the myelination status of previously reported Japanese patients with MCT8 deficiency based on magnetic resonance imaging (MRI). Case Reports: Four patients were genetically diagnosed with MCT8 deficiency at the age of 4-9 months. In infancy, MRI signal of myelination was observed mainly in the cerebellar WM, posterior limb of internal capsule, and the optic radiation. There was progression of myelination with increase in age. Discussion: We identified 36 patients with MCT8 deficiency from 25 families reported from Japan. The available MRI images were obtained at the age of <2 years in 13 patients, between 2 and 4 years in six patients, between 4 and 6 years in three patients, and at ≥6 years in eight patients. Cerebellar WM, posterior limb of internal capsule, and optic radiation showed MRI signal of myelination by the age of 2 years, followed by centrum semiovale and corpus callosum by the age of 4 years. Most regions except for deep anterior WM showed MRI signal of myelination at the age of 6 years. Conclusion: The sequential pattern of myelination in patients with MCT8 deficiency was largely similar to that in normal children; however, delayed myelination of the deep anterior WM was a remarkable finding. Further studies are required to characterize the imaging features of patients with MCT8 deficiency.
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Objectives Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations. Methods We enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH. Results We identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants. Conclusions The prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.
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Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/genética , Autoantígenos/genética , Preescolar , Hipotiroidismo Congénito/epidemiología , Análisis Mutacional de ADN , Oxidasas Duales/genética , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Yoduro Peroxidasa/genética , Proteínas de Unión a Hierro/genética , Japón/epidemiología , Masculino , Proteínas de la Membrana/genética , Receptores de Tirotropina/genética , Tiroglobulina/genética , Pruebas de Función de la Tiroides , Factor Nuclear Tiroideo 1/genéticaRESUMEN
Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. Pendrin, the iodide exporter that transports iodide to thyroid follicles, is responsible for Pendred syndrome, a disorder characterized by congenital hypothyroidism and hearing loss. However, thyroid hormone levels are basically normal in patients with Pendred syndrome, indicating the presence of another unknown iodide transporter. Here, we show that SLC26A7 is a novel iodide transporter in the thyroid. We observe that SLC26A7 is specifically expressed in normal thyroid tissues and demonstrate its function in iodide transport. Using whole-exome sequencing, we also find a homozygous nonsense mutation in SLC26A7 (c.1498 C > T; p.Gln500Ter) in two siblings with congenital goitrous hypothyroidism. The mutated SLC26A7 protein shows an abnormal cytoplasmic localisation and lacks the iodide transport function. These results reveal that SLC26A7 functions as a novel iodide transporter in the thyroid and its dysfunction affects thyroid hormonogenesis in humans and causes congenital goitrous hypothyroidism.
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Antiportadores/genética , Hipotiroidismo Congénito/genética , Bocio/congénito , Transportadores de Sulfato/genética , Animales , Antiportadores/metabolismo , Antiportadores/fisiología , Línea Celular , Preescolar , Codón sin Sentido , Perros , Femenino , Bocio/genética , Haplorrinos , Humanos , Recién Nacido , Masculino , Transportadores de Sulfato/metabolismo , Transportadores de Sulfato/fisiología , Glándula Tiroides/metabolismo , Hormonas Tiroideas/biosíntesisRESUMEN
AIMS/INTRODUCTION: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; also known as MODY2) is a benign hyperglycemic condition, which generally does not require medical interventions. The only known exception is increased birthweight and related perinatal complications in unaffected offspring of affected women. As previous data were obtained mostly from white Europeans, the present study analyzed the pregnancy outcomes of Japanese women with GCK-MODY to better formulate the management plan for this population. MATERIALS AND METHODS: The study participants were 34 GCK-MODY families whose members were diagnosed at Osaka City General Hospital during 2010-2017. A total of 53 pregnancies (40 from 23 affected women, 13 from 11 unaffected women) were retrospectively analyzed by chart review. RESULTS: Birthweights of unaffected offspring born to affected women were significantly greater as compared with those of affected offspring (P = 0.003). The risk of >4,000 g birthweight (16%), however, was lower as compared with that previously reported for white Europeans, and none of the offspring had complications related to large birthweight. Insulin treatment of the affected women resulted in a significant reduction in the birthweights of unaffected offspring. Perinatal complications including small-for-gestational age birthweight were found only in affected offspring born to insulin-treated women. CONCLUSIONS: In Japanese GCK-MODY families, unaffected offspring born to affected women were heavier than affected offspring. However, insulin treatment of affected women might not be advisable because of the lower risk of macrosomic birth injury, and an increased risk of perinatal complications in affected offspring.
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Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Glucoquinasa/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Recién Nacido , Japón/epidemiología , Masculino , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
Background Treatment for type 1 diabetes mellitus (T1DM) has greatly changed by the general use of insulin analogs and continuous subcutaneous insulin infusion (CSII). To investigate whether these advances have been translated into continued improvement in glycemic control in Japanese children and adolescents, we analyzed the registration data of the two consecutive recent cohorts of Japanese childhood-onset T1DM patients. Methods The registration data including hemoglobin A1c (HbA1c), hypoglycemia and insulin regimen were compared between the two cohorts (862 patients in the 2008 cohort and 1090 in the 2013 cohort). Results The proportion of subjects with multiple daily insulin injection therapy (MDI) and CSII significantly increased (p<0.0001) from 67.4% and 9.7% to 71.8% and 23.4%, respectively. In the 2013 cohort, almost all patients were treated with basal-bolus treatment using insulin analogs. The use of CSII increased in all age groups, especially in the age group 0-5 years. The rates of overall, moderate and severe hypoglycemia significantly declined from 10.24, 10.18 and 0.056 events/100 persons/period in the 2008 cohort to 0.66, 0.62 and 0.033 in the 2013 cohort (p<0.0001, <0.0001, 0.04), respectively. Contrarily, there were no significant changes in HbA1c values between the two cohorts. Conclusions The popularization of the basal-bolus treatment using insulin analogs hascontributed to a significant decrease in hypoglycemia. In contrast, the intensive insulin treatment may not be enough for the satisfactory improvement of glycemic control in Japanese children and adolescents with T1DM. Considerable points remain, such as diabetic education and support to motivate patients.
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Biomarcadores/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Sistemas de Infusión de Insulina , Insulina/uso terapéutico , Adolescente , Adulto , Glucemia/análisis , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Lactante , Recién Nacido , Insulina/análogos & derivados , Masculino , Pronóstico , Adulto JovenRESUMEN
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.
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Hipocalcemia/epidemiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adolescente , Niño , Preescolar , Femenino , Encuestas Epidemiológicas , Humanos , Hipocalcemia/sangre , Hipocalcemia/diagnóstico , Incidencia , Lactante , Japón/epidemiología , Masculino , Prevalencia , Raquitismo/sangre , Raquitismo/diagnóstico , Raquitismo/epidemiología , Evaluación de Síntomas , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/diagnósticoRESUMEN
BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH. METHODS: We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing. RESULTS: We detected 12 potentially pathogenic mutations in 11 families, with three having a mutation in ANOS1 (X-linked recessive); three and four having a mutation in FGFR1 and CHD7, respectively (autosomal dominant); and one having two TACR3 mutations (autosomal recessive). Among four patients with KS carrying a CHD7 mutation, one had perceptive deafness and two had a cleft lip/palate. CONCLUSIONS: The frequency of CHH genes in the Japanese was compatible with previous reports, except that CHD7 mutations might be more common. Furthermore, partial phenotype-genotype correlations were demonstrated in our cohort.
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Hipogonadismo/diagnóstico , Síndrome de Kallmann/diagnóstico , Mutación , Adolescente , Niño , Preescolar , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Proteínas de la Matriz Extracelular/genética , Femenino , Humanos , Hipogonadismo/genética , Lactante , Síndrome de Kallmann/genética , Masculino , Proteínas del Tejido Nervioso/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Adulto JovenRESUMEN
BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. RESULTS: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. CONCLUSION: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.
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Diabetes Mellitus/genética , Predisposición Genética a la Enfermedad , Mutación , Canales de Potasio de Rectificación Interna/genética , Receptores de Sulfonilureas/genética , Sustitución de Aminoácidos , Hiperinsulinismo Congénito/sangre , Hiperinsulinismo Congénito/tratamiento farmacológico , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/fisiopatología , Análisis Mutacional de ADN , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Monitoreo de Drogas , Resistencia a Medicamentos , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Epilepsia/fisiopatología , Femenino , Estudios de Asociación Genética , Gliburida/uso terapéutico , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Lactante , Enfermedades del Recién Nacido/sangre , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/genética , Enfermedades del Recién Nacido/fisiopatología , Insulina/uso terapéutico , Japón , Masculino , Canales de Potasio de Rectificación Interna/química , Trastornos Psicomotores/sangre , Trastornos Psicomotores/tratamiento farmacológico , Trastornos Psicomotores/genética , Trastornos Psicomotores/fisiopatología , Índice de Severidad de la Enfermedad , Receptores de Sulfonilureas/químicaRESUMEN
We report a Japanese female patient presenting with classic features of CHARGE syndrome, including choanal atresia, growth and development retardation, ear malformations, genital anomalies, multiple endocrine deficiency, and unilateral facial nerve palsy. She was clinically diagnosed with typical CHARGE syndrome, but genetic analysis using the TruSight One Sequence Panel revealed a germline heterozygous mutation in KMT2D with no pathogenic CHD7 alterations associated with CHARGE syndrome. Kabuki syndrome is a rare multisystem disorder characterized by five cardinal manifestations including typical facial features, skeletal anomalies, dermatoglyphic abnormalities, mild to moderate intellectual disability, and postnatal growth deficiency. Germline mutations in KMT2D underlie the molecular pathogenesis of 52-76% of patients with Kabuki syndrome. This is an instructive case that clearly represents a phenotypic overlap between Kabuki syndrome and CHARGE syndrome. It suggests the importance of considering the possibility of a diagnosis of Kabuki syndrome even if patients present with typical symptoms and meet diagnostic criteria of CHARGE syndrome. The case also emphasizes the impact of non-biased exhaustive genetic analysis by next-generation sequencing in the genetic diagnosis of rare congenital disorders with atypical manifestations.
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Purpose of developing the guidelines: The first guidelines for diagnosis and treatment of 21-hydroxylase deficiency (21-OHD) were published as a diagnostic handbook in Japan in 1989, with a focus on patients with severe disease. The "Guidelines for Treatment of Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) Found in Neonatal Mass Screening (1999 revision)" published in 1999 were revised to include 21-OHD patients with very mild or no clinical symptoms. Accumulation of cases and experience has subsequently improved diagnosis and treatment of the disease. Based on these findings, the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology further revised the guidelines for diagnosis and treatment. Target disease/conditions: 21-hydroxylase deficiency. Users of the guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, referring pediatric practitioners, general physicians; and patients.
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Purpose of developing the guidelines: Mass screening for congenital hypothyroidism started in 1979 in Japan, and the prognosis for intelligence has been improved by early diagnosis and treatment. The incidence was about 1/4000 of the birth population, but it has increased due to diagnosis of subclinical congenital hypothyroidism. The disease requires continuous treatment, and specialized medical facilities should make a differential diagnosis and treat subjects who are positive in mass screening to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, new findings on prognosis and problems in the adult phase have emerged. Based on these new findings, the 1998 guidelines were revised in the current document (hereinafter referred to as the Guidelines). Target disease/conditions: Primary congenital hypothyroidism. Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring patients to pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients.
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BACKGROUND: Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. METHODS: A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. RESULTS: CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. CONCLUSION: ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.
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Antagonistas de los Receptores de Endotelina , Estrés Oxidativo/efectos de los fármacos , Péptidos/farmacología , Animales , Aspartato Aminotransferasas/sangre , Creatinina/sangre , Peróxido de Hidrógeno/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Interleucina-6/metabolismo , PorcinosRESUMEN
BACKGROUND: This multicenter observational study was conducted to investigate the efficacy and safety of insulin detemir (detemir) for diabetes management in Japanese children and adolescents. METHODS: Data from the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes database were analyzed. Ninety children (32 boys, 58 girls; mean age, 11.9 ± 3.8 years) who transferred from a neutral protamine Hagedorn insulin or insulin glargine basal-bolus regimen to detemir basal-bolus therapy and who were observed for at least 12 months were identified. Clinical data obtained at 0, 3, 6, and 12 months were analyzed to determine the type of bolus insulin used, number and timing of detemir injections, detemir dose as a proportion of the total insulin dose, hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and frequency of severe hypoglycemia. RESULTS: Twelve months after switching to detemir, the detemir dose represented 39.8% of the total insulin dose, and 37.8% of patients were being treated with twice-daily injections. HbA1c and FBG were significantly reduced from baseline at 3 and 6 months but not at 12 months. Considering the seasonal HbA1c variation in the Japanese population, a separate analysis was performed using data for 65 children (21 boys, 44 girls; mean age, 11.6 ± 2.9 years) who switched to detemir during the winter. Subset analysis showed significant HbA1c reductions from baseline at all specified times. The incidence of severe hypoglycemia during detemir treatment was 4.4 episodes per 100 patient-years. CONCLUSIONS: Detemir is an effective and safe basal insulin for diabetes management in Japanese children and adolescents.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina de Acción Prolongada/administración & dosificación , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones Subcutáneas , Insulina Detemir , Japón/epidemiología , Masculino , Morbilidad/tendencias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Laparoendoscopic single-site surgery (LESS), a minimally invasive procedure, is gaining widespread acknowledgment in pediatric urology. We report the case of a 7-year-old girl with Turner's syndrome with 45,XO/46,XY mosaicism, for whom bilateral prophylactic gonadectomy using LESS was performed. Histopathological findings revealed bilateral streak gonads. The surgical and cosmetic outcome was excellent. Diagnostic and therapeutic laparoscopy is essential for accurate clinical management of patients with disorders of sex development. Although this is only a single case report, it supports the theory that LESS is an exceedingly practical and superior technique for such children, since it provides excellent magnification, as well as allowing normal psychological development owing to the concealed scar. Further studies and long-term follow-up are required to evaluate the benefits and limitations of applying LESS in pediatrics.