Clinical evaluation of recombinant human growth hormone in Noonan syndrome.

The objective of this study was to investigate the effect of administration of recombinant human growth hormone (hGH) in patients with Noonan syndrome. hGH was administered (0.5 IU/kg/week) to 15 patients with Noonan syndrome over a 2 year period.

Japanese familial patients with male-limited precocious puberty.

Familial male-limited precocious puberty (FMPP) is a rare disease caused by constitutively activating mutations in the luteinizing hormone receptor (LH-R) gene. In the present study, we analyzed the LH-R gene in members of a Japanese FMPP family. Two males of the family were affected and had a heterozygous M398T mutation; one patient developed pubertal signs as early as 2 years of age, and the other at 6 years of age.

Genetic and endocrinological evaluations of three 46,XX patients with congenital lipoid adrenal hyperplasia previously reported as having presented spontaneous puberty.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of adrenal and gonadal steroids. It was demonstrated that loss-of-function mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH and that 46,XX patients with CLAH develop spontaneous puberty. We had reported that three 46,XX patients with CLAH had presented spontaneous puberty and one of the patients had developed life-threatening ovarian cysts, before the etiology of CLAH had been clarified.

Growth and metabolic disturbances in a patient with total parenteral nutrition: a case of hypercalciuric hypercalcemia.

Hypercalciuria is a common side effect during total parenteral nutrition (TPN). We report a patient with long-term TPN, who demonstrated hypercalciuria, hypercalcemia and growth retardation. The patient is a six-year-old Japanese girl with Hirschsprung disease (jejunal agangliosis).

Analysis of the FGFR3 gene in Japanese patients with achondroplasia and hypochondroplasia.

It has been reported that mutations in the FGFR3 gene cause autosomal dominant forms of dwarfism, achondroplasia (ACH) and hypochondroplasia (HCH). In the present study, we analyzed the FGFR3 gene in 26 Japanese patients with ACH and 14 with HCH. Genomic DNAs of the patients were isolated from whole blood.

Bone mineral density in Turner syndrome: relation to GH treatment and estrogen treatment.

The bone mineral density (BMD) of the second metacarpal bone of the left hand was measured in 57 patients with Turner syndrome by the digital image processing (DIP) method to study the relations between the treatment regimen and their bone mineral density. BMD SD score in the patients who had started the GH treatment before 10 years old was within +/-2SD of the standard before 14 years, but the score decreased to below -2SD after 14 years. In the patients who had started GH treatment after 10 years old, BMD score were significantly lower than -2SD, although there was tendency to increased.

Acid-labile subunit (ALS) measurements in children.

Almost all of the serum IGFs are found in a ternary complex composed of IGF, IGFBP-3 and acid-labile subunit (ALS). It was reported that ALS levels were age- and sex-dependent. In the present study we measured serum ALS levels in 264 normal children (145 boys and 119 girls) aged from 5 days to 16 years, and 15 patients with growth hormone deficiency (GHD) aged from 11 months to 13 years.

Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia.

Objective: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH.

Methods: The subjects were three Japanese CLAH patients.

A Japanese family with autosomal dominant growth hormone deficiency.

Unlabelled: We report a 1-year-old Japanese boy and his father with isolated growth hormone deficiency II. In both cases, a G-->A transition of the first base of the donor splice site of intron 3 of the growth hormone-1 gene was detected. All unaffected family members were homozygous normal.

A novel frameshift mutation 840delA and a novel polymorphism D203A in the steroidogenic acute regulatory protein gene in a Japanese patient with congenital lipoid adrenal hyperplasia. Mutations in brief no. 117. Online.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomalrecessive disorder characterized by impaired production of all steroids including glucocorticoids, mineralocorticoids and sexsteriods. It has recently been reported that mutations in the steriodogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the StAR gene in a Japanese patient with CLAH.

[Childhood diabetes mellitus].

Long-term check of 68 type 1 diabetes patients (1978-1998); 23 under age 19, mean age 13.4 +/- 4.1 (group A) and 45 above age 20, mean age 26.

When and how to combine growth hormone with a luteinizing hormone-releasing hormone analogue.

The effect of combined treatment with growth hormone (GH) and a luteinizing hormone-releasing hormone (LHRH) analogue, or GH alone, on pubertal height gain was assessed in an uncontrolled study in 15 boys and 10 girls with GH deficiency (GHD). Seven boys and six girls were treated with GH alone (group 1), and eight boys and four girls were treated with a combination of GH and an LHRH analogue during puberty (group 2). Mean ages (+/- SD) at the start of GH treatment and at the onset of puberty were significantly lower in group 2 (8.

The regulatory effect of growth hormone on growth hormone-binding protein in human serum.

To study the acute and long-term effect of GH on its down-stream axis, we measured serum GH-binding protein (GHBP) by ligand-mediated immunofunctional assay. Diurnal changes in serum GHBP were determined by every 20-min sampling for 24 h in four normal short children. There were small or negligible fluctuations in serum GHBP levels, and no correlation with GH pulses was observed.

Nutrition related hormonal changes in obese children.

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.

GH and GnRH analog treatment in children who enter puberty at short stature.

It is well known that height at the onset of puberty is closely related to final height. To improve final height of short children who enter puberty at short stature, twenty-one short boys and six short girls were treated with a combination of GH and GnRH analog. The boys started the combination treatment at a mean age of 12.

A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) characterized by early-onset hypertension and hypokalemia is due to congenital deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Two isoforms of human 11 beta HSD are known, and the type 2 isoform (11 beta HSD2) has been recently shown to be responsible for AME. In this study we have analyzed the 11 beta HSD2 gene of a Japanese patient with AME.

[Sexual precocity].

Sexual precocity results from both GnRH-dependent and GnRH-independent mechanisms. The GnRH-dependent forms of precocious puberty can be treated effectively with long-acting agonist analogues of GnRH. However, for some children who have a poor growth rate during the analogue therapy, an additional growth hormone therapy should be considered to get them near to their normal final height.

Follow-up study of children with precocious puberty treated with cyproterone acetate. Ad hoc Committee for CPA.

A total of 1840 children and adolescents treated with cyproterone acetate (CPA) to block gonadal function, as a treatment for precocious puberty, short stature and other disorders, were registered to survey for the risk of developing hepatic tumors. Patients responding to follow-up numbered 1552 (85%). The cumulative dose and duration of CPA therapy for boys and girls were 110.

Homozygous Q258X mutation in the steroidogenic acute regulatory gene in a Japanese patient with congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. It has recently been reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the nucleotide sequences of exon 7 of the StAR gene in a Japanese CLAH patient with a karyotype of 47,XYY, and her parents.

Urinary biotinidase and alanine excretion in patients with insulin-dependent diabetes mellitus.

Twenty-four-hour urine specimens from 21 juvenile insulin-dependent diabetics and 10 healthy controls were compared with respect to biotinidase activity and alanine content. Urinary biotinidase activity was analysed by a newly developed high-performance liquid chromatography (HPLC) method. It was found that the excretion of biotinidase in urine was elevated in diabetics (7.

Apparent mineralocorticoid excess due to 11 beta-hydroxysteroid dehydrogenase deficiency: a possible cause of intrauterine growth retardation.

A Japanese boy with apparent mineralocorticoid excess (AME) is described. He was born with intrauterine growth retardation (IUGR) and elevated serum level of creatine phosphokinase (CPK). He was studied at 2 years of age because of polyurea and polydipsia of one year's duration and was found to have hypokalaemic alkalosis and sustained hypertension.

Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5.