Kenji Fujieda

Efficacy and Safety of Up to 8 Years of Long-term Growth Hormone Treatment in Short Children Born Small for Gestational Age in Japan: Analysis of the Subpopulation According to the Japanese Guideline.

The efficacy and safety of 8 yr of GH treatment was assessed in 44 Japanese children with small for gestational age (SGA) short stature who met the criteria for GH treatment initiation (height SD score (SDS) <–2.5 SD) of the Japanese guidelines. Height SDS in subjects improved throughout the study period, and average height SDS improved from –3.5 to –1.6 and from –3.4 to –1.9 in the 0.033/0.067 mg and 0.067/0.067 mg groups, respectively, after 8 yr of GH treatment. Delta height SD was approximately +2 after 4 yr of treatment, and ∆ IGF-1 showed a significant positive correlation with ∆ height SD after both 1 and 2 yr (r = 0.415 and 0.488, respectively) of treatment. There was no correlation between the age at the start of treatment and age at onset of puberty, and the median age at the onset of puberty in the subjects was almost the same as that in healthy children. In conclusion, clinically significant improvements in the height SDS was confirmed in short children born SGA after 8 yr of GH treatment without any safety problems.

Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother.

BACKGROUNDnIntrauterine transmission of cytomegalovirus (CMV) can occur even in CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly acquired CMV strain during pregnancy had a major role in such transmission. Although reactivation of latently infected CMV is another plausible cause, no direct evidence has been documented.nnnOBJECTIVESnWe sought to identify the route(s) and maternal risk factor of CMV infection that occurred in consecutive pregnancies and resulted in symptomatic congenital infections.nnnSTUDY DESIGNnA newborn identified with congenital CMV infection in our newborn screening program developed hearing loss and subsequent nystagmus. The mother had a history of an elective abortion due to a severe fetal CMV infection 32 months prior to delivery of this newborn. We analyzed maternal serological changes and compared CMV genomic sequences in specimens obtained from the aborted fetus and the present case. We also analyzed immunological functions of the mother.nnnRESULTSnOur major findings were as follows: (1) the aborted fetus and the present case were infected with the same strain. (2) The congenital infection that resulted in the abortion was due to a primary infection. (3) CMV DNA was undetectable in the mothers blood from 3 months after the abortion. These results strongly suggested that maternal viral reactivation caused the congenital infection in the present case. However, we could not find impairment of immunological functions in the mother.nnnCONCLUSIONSnViral reactivation in an apparently immunocompetent mother can cause symptomatic congenital CMV infection.

Analysis of expression and structure of the rat GH-secretagogue/ghrelin receptor (Ghsr) gene: roles of epigenetic modifications in transcriptional regulation.

In the current study, to elucidate the molecular basis of cell type-specific expression of the GH-secretagogue/ghrelin receptor type 1A (GHSR1A), we characterized the structure and putative promoter region of the rat Ghsr gene. We identified an alternative 5-untranslated first exon that contains multiple transcription start sites, and confirmed a 200-bp sequence proximal to this exon to be sufficient for basal promoter activity. A promoter-associated CpG island conserved across different species was found to be hypomethylated in Ghsr1a-expressing cell lines, while being heavily methylated in non-expressing cells. In cells with low or absent Ghsr1a expression, treatment with demethylating agents activated Ghsr1a transcription. Chromatin immunoprecipitation assays demonstrated Ghsr1a-expressing cells to display active histone modifications, whereas repressive modifications were present exclusively in other cell types. These results suggest epigenetic modifications at GHSR to play important roles in determining GHSR1A expression and abundance, and therefore the consequent sensitivity of cells to ghrelin.

Axial spondylometaphyseal dysplasia: Additional reports†‡

Axial spondylometaphyseal dysplasia (SMD) (OMIM 602271) is an uncommon skeletal dysplasia characterized by metaphyseal changes of truncal‐juxtatruncal bones, including the proximal femora, and retinal abnormalities. The disorder has not attracted much attention since initially reported; however, it has been included in the nosology of genetic skeletal disorders [Warman et al. (2011); Am J Med Genet Part A 155A:943–968] in part because of a recent publication of two additional cases [Isidor et al. (2010); Am J Med Genet Part A 152A:1550–1554]. We report here on the clinical and radiological manifestations in seven affected individuals from five families (three sporadic cases and two familial cases). Based on our observations and Isidors report, the clinical and radiological hallmarks of axial SMD can be defined: The main clinical findings are postnatal growth failure, rhizomelic short stature in early childhood evolving into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and function rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on fundoscopic examination and cone‐rod dystrophy on electroretinogram. The radiological hallmarks include short ribs with flared, cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. Equally affected sibling pairs of opposite gender and parental consanguinity are strongly suggestive of autosomal recessive inheritance.

Identification of a novel mutation in the exon 2 splice donor site of the POU1F1/PIT‐1 gene in Japanese identical twins with mild combined pituitary hormone deficiency

Contextu2002 To date, approximately 35 different POU1F1 mutations have been described in patients with familial and sporadic combined pituitary hormone deficiency (CPHD) from different ethnic backgrounds. The majority are missense mutations clustered within the conserved POU‐specific and POU‐homeo domains, encoded by exons 4 and 6, respectively.

Weight-for-height charts for Japanese children based on the year 2000 Report of School Health Statistics Research

Obesity during adulthood has become a major health problem that can lead to other serious illnesses, such as hypertension, heart disease, stroke, and type 2 diabetes mellitus, thereby causing increased overall mortality (1). Many studies have suggested that these conditions originate in childhood and that preventive measures against adult obesity should be started as early as possible (2). Although evaluations of adiposity are essential for this purpose, the measurement of body fat is complicated (3). Therefore, body mass index (BMI, kg/m2), relative body weight (obesity index), and other adiposity-related indices are normally used as surrogate markers of body fat in the health care system, including in school-based examinations. n nBMI and age-specific BMI percentiles are widely used in many countries, and have been proven to be closely related to adiposity in children (4). According to the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) growth references, obesity and overweight status are defined as a BMI that equals or exceeds the 95th percentile value for children and adolescents of the same age and sex (5). n nIn contrast, relative body weight is widely used in Japan. Relative body weight is the percentage of the median or standard body weight of children of the same height, and is called the obesity index. The obesity index is quite comprehensive and is easy to understand for the general public, including children and adolescents. n nAccordingly, weight-for-height charts for preschool-aged children were developed (6) (Fig. 1, a: boys; b: girls) and are printed in maternity health record books. These books are distributed to all pregnant women and are used to maintain and promote health in pregnant women, mothers, fetuses, infants, and preschool-aged children. n n n nFig. 1. n nWeight-for-height charts with +30%, +20%, +15%, 0%, –15%, and –20% lines (obesity index) for preschool-aged Japanese boys (a) and girls (b). Obtained from reference (8). n n n nBased on the use of weight-for-height charts for preschool-aged children, weight-for-height charts for children and adolescents should also be developed. Therefore, we analyzed the relationship between height and weight using the 2000 Report of School Health Statistics Research (7), and thereby constructed weight-for-height charts for school-aged children and adolescents. These charts will not only be practical for evaluating the obesity status of individual children, but also for performing studies of public health.