Metabolic and immunological assessment of small-for-gestational-age children during one-year treatment with growth hormone: the clinical impact of apolipoproteins.

Children born small for gestational age (SGA) are at a higher risk for metabolic disorders later in life. In this study, we aimed to characterize young SGA children without catch-up growth and evaluate the effects of GH treatment on endocrinological, metabolic, and immunological parameters. Study design is a one-year single hospital-based study included prospective observation of SGA patients during 12 months of GH treatment. Clinical and laboratory profiles of SGA children at baseline were compared with controls born appropriate size for age. Twenty-six SGA children (median age, 3.4 years) and 26 control children (median age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical, immunological, and endocrinological parameters were assessed at baseline and 1, 3, 6, 9, and 12 months after the start of GH treatment. As a result, median height SD score (SDS) of SGA children increased by +0.42 with 12-month GH treatment. Body mass index SDS was lower in SGA children than in controls. Serum apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH treatment. Serum leptin and resistin levels, which were lower in SGA children than in controls at baseline, did not change remarkably with GH treatment. Monocyte counts, which were lower in SGA patients at baseline, increased after GH treatment. Neutrophil counts significantly increased after GH treatment. Natural killer cell ratios, which were higher in SGA patients, decreased after GH treatment. In conclusion, there was no evidence suggesting metabolic abnormalities in SGA children. Serum apolipoprotein changes might predict the beneficial role of GH treatment in lowering cardiometabolic risk.

Placental mesenchymal dysplasia and fetal hematologic disorder.

Placental mesenchymal dysplasia (PMD) is a rare, recently recognized placental vascular anomaly. About 20% of patients with this placental anomaly have Beckwith-Wiedemann syndrome. We report a case of a phenotypically normal neonate with anemia and thrombocytopenia associated with PMD. Histologic examination of the placenta showed findings consistent with PMD, including chorangioma. The patient's hematologic abnormalities resolved during the week following birth. Normal phenotypic fetuses with PMD seem to exhibit hematologic disorders at birth in some cases, especially in the presence of chorangioma.

N-terminal pro-brain natriuretic peptide as a useful predictor of early surgery in neonates with congenital heart diseases: a prospective observational study.

Pediatric studies have found a correlation between the clinical heart failure score and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. However, the clinical usefulness of this marker remains unclear in neonates. At hospitals without pediatric cardiologists, neonatologists or general pediatricians must judge whether surgery is indicated and transfer patients to a specialized hospital in a timely fashion as required. Thus, we tested the hypothesis that increased NT-proBNP levels predict short-term outcomes in neonates with congenital heart diseases (CHDs) and are thus a useful tool for evaluating clinical status and guiding treatment. Subjects were term or near-term newborns (≥36 weeks' gestation) with CHDs confined to left-to-right shunt lesions. Clinical parameters and NT-proBNP levels were measured on the first 7, 14, 21, and 28 days of life (DOL). We divided patients into a surgical (n = 7) and a conservative-treatment group (n = 21), and then compared clinical variables and outcomes between the groups. In the surgical group, NT-proBNP levels had a tendency to increase during the first 14 postnatal days and were significantly greater than in the conservative-treatment group on 7 DOL [median (range), 13,983 pg/mL (4,732-26,524) vs. 1,954 pg/mL (671-10,881); p = 0.0028] and on 14 DOL [29,274 pg/mL (14,006-33,740) vs. 2,050 pg/mL (1,304-9,250); p = 0.0055]. In contrast, NT-proBNP levels tended to decrease sequentially in the conservative-treatment group. The values of additional markers, such as mean NT-proBNP level on 7 and 14 DOLs (M7-14) and NT-proBNP level on 14 DOL minus that on 7 DOL (Δ7-14), were both significantly greater in the surgical group than in the conservative-treatment group. To examine the usability of M7-14 and Δ7-14 when the difference and mean cut-off levels were set at 10,000 and 3,000 pg/mL, respectively, the sensitivity and specificity were both 100 %. In neonates who had CHDs with left-to-right shunt, analysis of the association between clinical variables and short-term outcomes showed that NT-proBNP, especially M7-14 and Δ7-14, is a useful predictor of early surgery.

Coagulopathy in patients with late-onset ornithine transcarbamylase deficiency in remission state: a previously unrecognized complication.

The late-onset type of ornithine transcarbamylase (OTC) deficiency is almost asymptomatic before an abrupt onset of metabolic crisis in adolescence. This study focused on coagulopathy in OTC deficiency. We collected laboratory data regarding coagulation from OTC-deficient patients in Kyushu University Hospital in Japan or from cases reported from previous articles. Five patients with late-onset OTC deficiency, admitted to Kyushu University Hospital at the first metabolic attack or who presented at the outpatient clinic in the hospital, were analyzed, and 3 additional cases of OTC deficiency with coagulopathy in previous articles were included. As a result, the blood ammonia levels in these patients were remarkably high at the time of the metabolic attack, and prothrombin times were far below the normal level. The prothrombin times remained significantly abnormal on remission, despite almost normal levels of blood ammonia, serum aspartate aminotransferase, and alanine aminotransferase. Coagulation abnormality is a previously unidentified complication of OTC deficiency in remission state. This information will aid in the identification of patients with OTC deficiency before a lethal metabolic crisis occurs during adolescence.

Bilateral stenosis of carotid siphon in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease, caused by a de novo mutation of lamin-A gene, LMNA G608G. Accumulation of abnormal lamin-A (progerin) compromises nuclear membrane integrity and results in the accelerated senescence. Affected patients show a typical feature of birdlike face, alopecia, sclerotic skin, loss of subcutaneous fat, and short stature with advancing years. Neonatal scleroderma is the first presentation, although early diagnosis is challenging. The leading cause of death is cardio-/cerebro-vascular accidents associated with atherosclerosis. However, not all findings may recapitulate the aging process. We herein report a 9-year-old Japanese male with HGPS who developed cerebral infarction. The genetic study of peripheral blood-derived DNA determined a heterozygous c.1824C>T mutation, p.G608G. Telomere length of lymphocytes was normal. Bilateral stenosis of carotid siphons was prominent, while systemic arteriosclerosis was unremarkable assessed by the ankle-brachial index, carotid ultrasound imaging and funduscopic study. HGPS patients have marked loss and functional defects in vascular smooth muscle cells, leading to the vulnerability to circulatory stress. Symmetrical stenosis of siphons might occur as a distinctive cerebral vasculopathy of HGPS, rather than simple vascular senescence. Peripheral blood study on LMNA G608G and telomere length could screen progerias in infancy for early therapeutic intervention.

A girl with Hajdu-Cheney syndrome and premature ovarian failure.

Hajdu-Cheney syndrome is an autosomal dominant disorder characterized by acroosteolysis of the distal phalanges associated with digit abnormalities, distinctive craniofacial changes, dental anomalies, and a proportionate short stature. The pubertal development of children with Hajdu-Cheney syndrome is usually normal in the literature, although we here first describe a girl who was found to have Hajdu-Cheney syndrome accompanied with premature ovarian failure. She showed a follicle-stimulating hormone-dominant response on luteinizing hormone-releasing hormone test and did not show any sex differentiation abnormality or adrenal steroid hormone deficiency. On the basis of the findings in our patient, premature ovarian failure may be a complication of Hajdu-Cheney syndrome and thus an early endocrinological evaluation of patients is important.

The signal transducer and activator of transcription 5B gene polymorphism contributes to the cholesterol metabolism in Japanese children with growth hormone deficiency.

BACKGROUND AND AIMS: GH plays a significant role in the lipid metabolism. In this study, we focused on the JAK2 - signal transducer and activator of the transcription 5 (STAT5) pathway, which transmit the signals from the GH receptor, and selected the STAT5A/B gene as a candidate for the regulation of lipid metabolism in GH deficiency (GHD). DESIGN AND PARTICIPANTS: The study population comprised 83 children with idiopathic GHD. The serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and the non-HDL cholesterol (non-HDL-C) levels were monitored before and at 3, 6, 9 and 12 months after starting GH treatment. The height, weight, body mass index, and serum insulin-like growth factor-I (IGF-I) level were also measured before and 12 months after starting the GH treatment. For the genetic analysis of the STAT5A/B gene, five tag SNPs were selected using the tag SNP picker programme on the homepage of the HapMap project. The evaluation of promoter activity of the -44816A/G SNP in the STAT5B gene was performed by a luciferase assay in vitro. RESULTS: The TC and non-HDL-C levels were gradually decreased during the GH treatment. Five tag SNPs (rs4029774, rs6503691, rs9900213, rs16967637 and rs2272087) were picked up for the STAT5A/B gene, and the genetic study demonstrated that the paediatric GHD patients who were heterozygotes or homozygotes of minor alleles of the analysed SNPs in the same block of the STAT5B gene showed significantly higher serum TC or non-HDL-C levels both before and after GH treatment for 12 months. Most of the SNPs also demonstrated significant differences among genotypes in the decreases in serum TC or non-HDL-C levels during the 12 months of GH treatment. A luciferase assay showed that the -44816A/G SNP (rs4029774) in the STAT5B gene functionally affected the expression level in vitro. CONCLUSION: These results indicate that STAT5B may therefore play a role in regulating the cholesterol metabolism in children with GHD.

Biotin deficiency in a glycogen storage disease type 1b girl fed only with glycogen storage disease-related formula.

Glycogen storage disease type I is an autosomal recessive disorder caused by the defect in the glucose-6-phosphate enzyme system. Frequent intake of glucose-containing glycogen storage disease formula, uncooked cornstarch, or both, are usually needed to maintain normal blood glucose level. We report a glycogen storage disease type 1b girl with biotin deficiency caused by an exclusive glucose-containing glycogen storage disease formula for years, presenting with the appearance of severe skin lesions, and diagnosed by urinary organic acid analysis by gas chromato-spectrometry, and blood acylcarnitine analysis by tandem mass-spectrometry.