Acute Cheilitis Associated with Oseltamivir after Influenzae A Infection.

Oseltamivir is a neuraminidase inhibitor used to treat acute influenza A or B in adult and pediatric patients. Adverse reactions are usually mild. Here, we report novel side effects associated with oseltamivir. The patient was an 11-year-old girl who developed lower lip cheilitis and stomatitis, after taking oseltamivir. Her symptoms and signs resolved within 36 h of oseltamivir discontinuation. She has clinically fully recovered and has remained well.

Olanzapine Overdose in a Two-Year-Old Girl Resulting in Both High Serum and Plasma Levels.

The antipsychotic olanzapine is used increasingly to treat various psychiatric illnesses. Accidental olanzapine overdose is uncommon among children. Here, we report a case of a child presenting with an unexplained coma. Accidental ingestion of olanzapine (20 mg) was confirmed by measurement of drug concentrations in both serum and plasma.

Fibrillin I gene polymorphism is associated with tall stature of normal individuals.

In order to test the hypothesis that polymorphisms of the Marfan syndrome gene (FBN1) might affect the stature (height) of normal individuals, we genotyped three exonic SNPs on 428 males, 219 with tall stature (>2 SD) and 209 with normal stature (within +/-1 SD). One of the SNPs, rs8033037, in exon 15 showed a significant correlation (P = 0.0061) with the adult height, suggesting that FBN1 is one of the 'stature genes' of normal individuals.

Prevalence of Mutations in the FGFR3 Gene in Individuals with Idiopathic Short Stature.

FGFR3 (fibroblast growth factor receptor 3) is a gene responsible for the most common form of osteodysplasia, achondroplasia, which results in extreme short stature. An allelic disorder, hypochondroplasia, however, presents with a much milder phenotype and is sometimes indistinguishable from idiopathic short stature. In this study, in order to test the possibility of the mildest end of hypochondroplasia being labeled as idiopathic short stature and the possibility of polymorphism of FGFR3 acting as one of the stature genes of normal individuals, we examined the prevalence of sequence alterations of the FGFR3 gene among individuals diagnosed clinically with idiopathic short stature. Sequencing analysis of all exons of the FGFR3 gene on 54 individuals with idiopathic short stature did not reveal any sequence variations related to the stature of the individuals. These results suggest that hidden hypochondroplasia among idiopathic short stature individuals is not a common occurrence and the contribution of polymorphism of the FGFR3 gene as a determinant of stature in normal individuals is small if any.

Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism.

Mutations in the gene coding for hepatocyte nuclear factor-1beta (HNF-1beta) have been known to cause a form of maturity-onset diabetes of the young (MODY5), which is usually characterized by dominantly inherited adolescence-onset diabetes mellitus associated with renal cysts. This report, however, describes recurrence of a novel missense mutation in the HNF-1beta gene, S148W (C443G), in two sibs, one with neonatal diabetes mellitus and the other with neonatal polycystic, dysplastic kidneys leading to early renal failure. The former patient had only a few small renal cysts with normal renal functions, and the latter had only a transient episode of hyperglycemia, which resolved spontaneously. Interestingly, both parents were clinically unaffected, and PCR restriction fragment length polymorphism analysis showed that the mother was a low-level mosaic of normal and mutant HNF-1beta, which suggested that the recurrence was caused by germline mosaicism. This is the first report of permanent neonatal diabetes mellitus caused by a mutation of the HNF-1beta gene as well as the first report of germline mosaicism of this gene. In addition, the two cases described here show that additional factors, genetic or environmental, can have a significant influence on the phenotypic expression of HNF-1beta mutations.

Earlier initiation of GH therapy does not influence adult height but enables earlier start of pubertal induction in children with multiple pituitary hormone deficiency.

OBJECTIVE: For patients with GH and gonadotrophin deficiency, adult height and sexual maturation are important not only for their physical but also psychological status. GH therapy is usually initiated soon after diagnosis but the differences in the age for initiation of therapy have not been previously examined. In this study, we assessed the influence of timing of initiation of GH therapy on adult height and the time of initiation of pubertal induction. DESIGN, PATIENTS AND MEASUREMENTS: Height-related data from 16 short children (13 boys and three girls) with GH and gonadotrophin deficiency who reached adult height after 10.9 +/- 2.3 years of GH therapy were analysed retrospectively. RESULTS: Adult height (0.00 +/- 0.69 SD) improved remarkably compared to height SDS at the start of GH therapy (-3.75 +/- 0.94 SD). The age at which GH therapy was started ranged from 3.2 to 12.0 years, but we found that such a difference in age did not affect adult height. However, an earlier start of GH therapy allowed earlier pubertal induction without loss of height potential. CONCLUSIONS: Earlier initiation of GH therapy is not required for normalization of adult height in patients with GH and gonadotrophin deficiency but it makes earlier pubertal induction possible, which is important for quality of life.

Parental origin of normal X chromosomes in Turner syndrome patients with various karyotypes: implications for the mechanism leading to generation of a 45,X karyotype.

The parental origin of the X chromosome of 45,X females has been the subject of many studies, and most of them have shown that the majority (60-80%) of the X chromosomes are maternal in origin. However, studies on the parental origin of normal X chromosomes are relatively limited for Turner syndrome (TS) females with sex chromosome aberrations. In this study, we used PCR-based typing of highly polymorphic markers and an assay of methylation status of the androgen receptor gene to determine the parental origin of normal X chromosomes in 50 unbiased TS females with a variety of karyotypes. Our results showed a higher paternal meiotic error rate leading to the generation of abnormal sex chromosomes, especially in the case of del(Xp) and abnormal Y chromosomes. Isochromosome Xq and ring/marker X chromosomes, on the other hand, were equally likely the result of both maternal and paternal meiotic errors. A thorough review of previous results, together with our data suggests, that the majority of TS karyotype are caused by paternal meiotic errors that generate abnormal sex chromosomes, and that most 45,X cells are generated by mitotic loss of these abnormal sex chromosomes, resulting in maternal X dominance in these cells.

Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications.

Propionic acidemia [MIM 606054] is a form of organic acidemia caused by genetic deficiency of propionyl-CoA carboxylase (PCC) and characterized by attacks of severe metabolic acidemia and hyperammonemia beginning in the neonatal period or in early infancy. There are, however, patients who have higher PCC activities and present later with unusual symptoms, such as mild mental retardation or extrapyramidal symptoms, sometimes even without metabolic acidosis. Through the neonatal screening of more than 130,000 Japanese newborns we detected a frequency of patients with propionic acidemia more than ten times higher than previously reported, most of them with milder phenotypes. The mutational spectrum was quite different from that of patients with the severe form and there was a common mutation (Y435C) in the beta subunit of the PCC gene (PCCB). Since patients with the mild form could present with unusual symptoms and therefore could easily remain unrecognized, it is important to identify those patients and clarify their natural history. Molecularly, one of the mutations (A1288C) caused an unusual pattern of multiple exon skipping and another unidentified mutation lead to the absence of mRNA. Taking into consideration previous findings regarding PCCB mutations, it appears that this gene is particularly prone to posttranscriptional modifications such as missense mediated exon skipping, mRNA decay, or rapid product degradation.