Susumu Kanzaki

Serum levels of carboxyterminal propeptide of type I procollagen and pyridinoline crosslinked telopeptide of type I collagen in normal children and children with growth hormone (GH) deiciency during GH therapy

In this study, we investigated age-related changes in serum levels of both the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline crosslinked telopeptide of type I collagen (ICTP) to elucidate bone formation and resorption, respectively, in 200 normal Japanese children (141 males and 59 females, age range 0-16 years). Furthermore, to clarify the effect of GH on bone turnover, we measured serum PICP and ICTP in 26 growth hormone (GH)-deficient children (20 males and 6 females, age range 4-15 years) who showed significant bone growth during recombinant human GH therapy. In the normal children, the curves for age-related changes in both serum PICP and ICTP levels almost paralleled that of the standard height velocity curve in both sexes. The serum levels of both peptides were higher than those in adults, and the peak increases corresponded with the timing of the adolescent growth spurt. Furthermore, the serum levels of PICP and ICTP were significantly correlated with the height velocity. In the GH-deficient patients, the serum ICTP levels before GH therapy were lower than those in age- and sex-matched controls. Both PICP and ICTP levels in serum increased significantly at the beginning of GH therapy. Furthermore, the percent increase in PICP after 1 month of GH treatment was positively correlated with the percent increase in height velocity during 1 year of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty

OBJECTIVE Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultrasensitive assay for children.

Molecular defects in achondroplasia and the effects of growth hormone treatment

Seino Y, Moriwake T, Tanaka H, Inoue M, Kanzaki S, Tanaka T, Matsuo N, Niimi H. Molecular defects in achondroplasia and the effects of growth hormone treatment. Acta Pa; diatr 1999; Suppl 428: 118–20. Stockholm. ISSN 0803–5326

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children

Abstract: The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually.

Malignant osteopetrosis treated with high doses of 1α-hydroxyvitamin D3 and interferon gamma

A male infant with malignant osteopetrosis was treated with high doses of 1 α -hydroxyvitamin D 3 and interferon gamma. Therapy with 1 α -hydroxyvitamin D 3 increased the serum calcium level despite the markedly elevated serum level of 1 α ,25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression.

Systematic molecular analyses of SHOX in Japanese patients with idiopathic short stature and Leri-Weill dyschondrosteosis

The etiology of idiopathic short stature (ISS) and Leri–Weill dyschondrosteosis (LWD) in European patients is known to include SHOX mutations and copy-number variations (CNVs) involving SHOX and/or the highly evolutionarily conserved non-coding DNA elements (CNEs) flanking the gene. However, the frequency and types of SHOX abnormalities in non-European patients and the clinical importance of mutations in the CNEs remains to be clarified. Here, we performed systematic molecular analyses of SHOX for 328 Japanese patients with ISS or LWD. SHOX abnormalities accounted for 3.8% of ISS and 50% of LWD cases. CNVs around SHOX were identified in 16 cases, although the ~47 kb deletion frequently reported in European patients was absent in our cases. Probably damaging mutations and benign/silent substitutions were detected in four cases, respectively. Although CNE-linked substitutions were detected in 15 cases, most of them affected poorly conserved nucleotides and were shared by unaffected individuals. These results suggest that the frequency and mutation spectrum of SHOX abnormalities are comparable between Asian and European patients, with the exception of a European-specific downstream deletion. Furthermore, this study highlights the clinical importance and genetic heterogeneity of the SHOX-flanking CNVs, and indicates a limited clinical significance of point mutations in the CNEs.

Hypothyroidism and hypoparathyroidism in an 11 year old boy with hemochromatosis secondary to aplastic anemia

This is the first reported case, to our knowledge, of hypoparathyroidism and hypothyroidism due to secondary hemochromatosis with onset during childhood. The patient was a boy with refractory aplastic anemia in whom primary hypothyroidism and hypoparathyroidism became apparent at the age of 10 and 11 years old, respectively. He had received a total of 100 L of transfused blood by the age of 10 years. The patient showed poor annual height gain due to primary hypothyroidism, together with hypocalcemia, cataract and intracranial calcification due to hypoparathyroidism. The early appearance of both thyroid and parathyroid dysfunction in this patient may have been due to the delay of initiation of iron‐chelating agents and liver dysfunction due to hepatitis type C.

Urinary glycylprolyl dipeptidyl aminopeptidase (GP‐DAP) in insulin‐dependent diabetic patients

Urinary glycylprolyl dipeptidyl aminopeptidase (GP‐DAP) concentrations were determined in 36 insulin‐dependent diabetic children aged 4–18 years with a duration of diabetes ranging from 1 month to 14 years. Abnormal urinary GP‐DAP concentrations were found in 19 of the 36 patients. Twelve of 27 patients without microalbuminuria also had increased urinary concentrations of GP‐DAP. There was a significant correlation between urinary GP‐DAP and plasma fructosamine (r= 0.52, p < 0.001). Our data suggest that urinary GP‐DAP may be used as a marker for diabetic nephropathy. However, there is also a possibility that increased urinary GP‐DAP concentrations are functionally related to poor metabolic control. Longitudinal studies are needed to establish the clinical usefulness of urinary GP‐DAP.

Pericentric inversion inv(2) (p11.2q21) associated with Treacher Collins−Franceschetti syndrome

Pericentric inversions are among the most common chromosomal rearrangements in humans. Such rearrangements of chromosome 2 are the second most common inversions. Treacher Collins–Franceschetti syndrome is an autosomal dominant disorder with anomalies of the orbit, face and ear positioning. A causative gene for this syndrome has been isolated from chromosome 5q32–33.1.1 It is suggested that haploinsufficiency is the underlying mechanism. However, Dixon suggested the possibility of genetic heterogeneity2 due to a number of different chromosome anomalies associated with the syndrome.3–6 Here we describe a new patient of Treacher Collins– Franceschetti syndrome associated with pericentric inversion of chromosome 2.

Suppression of nocturnal growth hormone secretion in epilepsy with continuous spike‐waves during slow‐wave sleep

modify hormone secretion from the anterior pituitary gland.1–3 That is, transient postictal rises of serum prolactin (PRL) have been recorded following generalized tonic–clonic and some partial seizures.1,2 However, it remains unsettled what effect epileptiform discharges have on growth hormone (GH) secretion. Matthew and Woods4 and Valdizan et al.5 reported that there were no significant changes in nocturnal GH secretion observed in patients with various types of seizures. Takeshita et al., however, reported that serum GH levels were elevated after generalized tonic–clonic seizures.3 Epilepsy with continuous spike-waves during slow-wave sleep (CSWS)6 is characterized by electrical status epilepticus during slow-wave sleep.7 As nocturnal GH secretion usually shows its highest level during the first slow-wave sleep phase (stages III and IV),8 massive spike-wave discharges during slow-wave sleep in patients with CSWS may affect nocturnal GH secretion. We, therefore, studied the effects of diffuse spike and wave discharges on nocturnal GH secretion in epileptic patients with CSWS.