Lead is highly toxic to the human body and children are much more vulnerable to lead toxicity than adults. Many studies have revealed that relatively low levels of blood lead can adversely affect human health, especially childhood growth and development. Blood lead levels (BLL) of children and adults have been decreasing recently almost all over the world, but a safety level for blood lead does not exist, and lead exposure is still a serious health problem especially for fetuses and children. Maternal lead burden causes fetal lead exposure and increases the risk of abortions, prematurity, low birth weight, and some minor anomalies. Infant BLL are inversely associated with weight gain. A negative relationship between somatic growth and BLL in children has been revealed. It has been suggested that lead exposure causes decrease of gonadotropin secretion of adolescents and delay of pubertal development. Several studies have revealed that children who are exposed to cigarette smoke have higher BLL than children who are not. Children should be protected from cigarette smoke for the purpose of avoiding the risk of increased BLL which might adversely affect their intellectual development and physical growth.

抄録全体を表示

Serum phosphate levels are regulated in both calcium-dependent and -independent fashions. Active vitamin D increases while PTH decreases serum phosphate levels in association with the elevation of serum calcium. On the other hand, a calcium-independent phosphaturic factor, historically called phosphatonin is believed to exert a physiological function based on findings in hereditary and tumor-induced diseases characterized by hypophosphatemia with normocalcemia. Among them, autosomal dominant hypophosphatemic rickets (ADHR) has contributed greatly to its elucidation because the gene responsible for ADHR encodes fibroblast growth factor 23 (FGF23) that has been found to have a phosphaturic effect. In addition, FGF23 has been proved to be involved in most cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets that are also characterized by hypophosphatemia and normocalcemia. Moreover, familial tumoral calcinosis, which represents the metabolic mirror image of hypophosphatemic conditions, is caused by a loss-of-function mutation in the FGF23 gene in some patients. Very recently, hereditary hypophosphatemic rickets with hypercalciuria has been found to be caused by mutations in the SLC34A1 gene which encodes a type of sodium phosphate cotransporter. These findings may provide new strategies for treating patients with abnormal phosphate metabolism.

抄録全体を表示

Gitelman syndrome (GS) is a renal tubular disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria due to defective tubular reabsorption of magnesium and potassium. This disease is caused by mutations of the thiazide-sensitive Na-Cl cotransporter (NCCT) gene, SLC12A3. Manifestations of GS are heterogeneous, from asymptomatic to mild symptoms of cramps and easy fatigue, to tetany and paralysis. Polydipsia, polyuria, and nocturia are also frequent in GS patients. Here we describe two Japanese patients with GS followed as nocturnal enuresis. In the first patient, occasional muscle cramps, easy fatigue and headache led to the diagnosis of GS. The parents of this patient reported that he had been affected by polydipsia and polyuria, especially nocturnal enuresis from early childhood. The second patient was referred to our clinic because of muscular weakness and cramps. He had a past history of transient muscle weakness and muscle cramps. He had also suffered from nocturnal enuresis since 3 yr of age. Laboratory findings of these patients were consistent with those of GS. Sequencing analysis of the SLC12A3 gene from two patients showed four mutations, which were previously reported. In our two patients, their manifestations had been underestimated and the correct diagnosis was delayed. GS is generally likely to be benign, however signs of GS are found in early childhood. Especially, we must recognize that nocturnal enuresis is frequent in symptoms of GS.

抄録全体を表示

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are caused by mutations of the WT1 gene. These disorders are characterized by renal disease, abnormality of male sex differentiation, and Wilms' tumor and gonadoblastoma. There have been few reports on gonadal function in a large series of patients with mutations of the WT1 gene. Here, we evaluated the relation between gonadal function and the phenotype of external genitalia in 15 Japanese patients with WT1 mutations. We confirmed three sets of information. First, if a diagnosis of DDS and FS is arrived at by genetic analysis, there are some overlaps in the phenotypes of external genitalia and renal complications. Second, the responses of serum T for the human CG (HCG) loading test coincided with the phenotype of external genitalia in both DDS and FS, except two patients. One DDS patient had male type external genitalia with a low level of serum T response, and one FS patient had complete female external genitalia despite a definite serum T response to HCG stimulation. Third, four FS patients had incomplete development of pubic hair, together with low DHEA-S levels.

抄録全体を表示

The prevalence of abnormalities in androgen receptor gene (AR) among patients with ambiguous genitalia is unknown. Moreover, endocrinological data from prepubertal patients with AR mutation are very limited. Thus, the aim of this study was to examine the prevalence of abnormalities in AR among patients with both ambiguous genitalia, which was defined as a combination of two or more genital abnormalities (i.e. hypospadias, microphallus (penile length < 25 mm), hypoplastic scrotum, bifid scrotum, undescended testis) in this study, and normal to elevated T levels. We also compared the endocrinological data of prepubertal patients with AR mutation and ambiguous genitalia with that of those without the AR mutation. We screened 26 Japanese prepubertal 46,XY patients (five from three families were included) with both ambiguous genitalia and normal to elevated T levels. Mutations in AR were found in three (two of the three were related). Among the 23 patients without mutation in AR, the steroid 5-alpha-reductase 2 gene (SRD5A2) was also examined in eight patients with elevated T/dehydrotestosterone ratio after the hCG (>10) or with undervirilized family members. No mutation in SRD5A2 was found. Characteristics of the three patients with mutation in AR were compared with the 23 patients without mutation. In two patients, basal T levels (0.3, 0.2 ng/ml) and peak T levels after the hCG tests (8.3, 8.5 ng/ml) tended to be higher, and the peak LH/ peak FSH ratios after the GnRH tests (4.6, 4.0) were higher than in patients without mutation, at the ages of 1 yr and 9 mo and 3 yr and 8 mo, respectively. In conclusion, an abnormality in either AR or SRD5A2 was not common among patients with ambiguous genitalia and normal testosterone secretion. Elevated peak LH/peak FSH ratio (≥4) after the GnRH test in addition to detectable basal T levels and elevated peak T levels after the hCG test may infer AR abnormality in prepubertal patients with ambiguous genitalia at the age of one and over, although further study is needed, because our data were limited.

抄録全体を表示

This study examined discrepancies between the perceptions of physicians treating short children with GH deficiency (GHD) using GH replacement therapy (GHRT) and the perceptions of the parents of these children and identified the major causes of parental anxiety. Three attending pediatric endocrinologists and the parents of 31 GHD children participated in this study. The physicians and parents completed a specially designed questionnaire to rate the types and degrees of psychosocial problems that GHD children might experience. For 6 of the first 11 questions, the physicians rated psychological problems differently than the parents did, tending to over- or underestimate parental concerns. This discrepancy did not disappear with treatment. However, the difference in the perception of anxiety between the physicians and parents changed for issues regularly discussed between them. Physicians and nurses were ranked as the most reliable providers of information. The parents of children who had previously undergone GHRT were a highly desired source of information. Psychosocial problems remain largely unaddressed by endocrinologists. Endocrinologists treating short stature are encouraged to be more involved in understanding parents' anxieties, evaluation of misperceptions concerning parents' expectations, and addressing these issues in future communication with parents. Support by experienced psychologists may help endocrinologists with this issue.

抄録全体を表示