Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Guidance on the management of familial hypercholesterolaemia in Hong Kong: an expert panel consensus viewpoin.

In 2016, meetings of groups of physicians and paediatricians with a special interest in lipid disorders and familial hypercholesterolaemia were held to discuss several domains of management of familial hypercholesterolaemia in adults and children in Hong Kong. After reviewing the evidence and guidelines for the diagnosis, screening, and management of familial hypercholesterolaemia, consensus was reached on the following aspects: clinical features, diagnostic criteria, screening in adults, screening in children, management in relation to target plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis, lifestyle and behaviour modification, and pharmacotherapy.

Screening for dysglycaemia by oral glucose tolerance test should be recommended in all women with polycystic ovary syndrome.

STUDY QUESTION: Should fasting glucose (FG) or an oral glucose tolerance test (OGTT) be used to screen for dysglycaemia in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: A full OGTT should be recommended as the screening method for dysglycaemia in women with PCOS, regardless of BMI or family history of diabetes mellitus (DM). STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 467 Chinese women diagnosed with PCOS by the Rotterdam criteria between January 2010 to December 2013. PARTICIPANTS, SETTING, METHODS: The study was done at a university hospital in Hong Kong. All subjects underwent a 75 g OGTT after overnight fasting. We evaluated the performance of FG alone, when compared with the full OGTT, in identifying subjects with dysglycaemia (prediabetes or DM, according to the 2010 diagnostic criteria of the American Diabetes Association). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 467 subjects, 58 (12.4%) had dysglycaemia, among which 46 (9.8%) had prediabetes and 12 (2.6%) had DM, including 4 with known DM. Of the 46 subjects with prediabetes, 25 (54.3%) had normal FG and of the 8 subjects with screened DM in this study, 1 (12.5%) had normal FG. The sensitivity of FG alone in screening for prediabetes, DM and overall dysglycaemia were 45.7, 87.5 and 48.1%, respectively, i.e. missing 54.3% of prediabetes and 12.5% of DM cases as defined by the OGTT. Among the 54 subjects with screened dysglycaemia, 20 (37.0%) had BMI < 25 kg/m(2) and 35 (64.8%) had no family history of DM. LIMITATIONS, REASONS FOR CAUTION: We only reported on the biochemical diagnosis of DM based on a single time point. In clinical practice, confirmatory results at another time point is required for definitive diagnosis in asymptomatic subjects. WIDER IMPLICATIONS OF THE FINDINGS: There is an ongoing debate as to whether FG or an OGTT should be used as a screening method for dysglycaemia in women with PCOS. Some guidelines also recommend glucose screening only in those who are overweight and/or having family history of diabetes (DM). There have been scarce data on this issue in the Chinese population, which the current study aims at addressing. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a research grant from the Hong Kong Obstetrical and Gynaecological Trust Fund, as well as internal research funding of the Department of Obstetrics and Gynaecology, The University of Hong Kong. All authors have no competing interests.

A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene.

Osteoporosis pseudoglioma syndrome (OPPG) is an autosomal recessive disorder due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we report two novel missense mutations found in a southern Chinese family of a non-consanguineous marriage. Three out of four children had blindness, low bone mineral density (BMD) and multiple fractures in their childhood. Genotyping by DNA sequencing demonstrated 2 new mutations in exon 7 of the LRP5 gene. Tryptophans at amino acid residue positions 478 and 504 were replaced by arginine (W478R) and cysteine (W504C), respectively. While the parents that possessed either heterozygous W478R or W504C were apparently normal, all affected subjects were compound heterozygotes for the W478R and W504C mutations in the LRP5 gene. W478R is located immediately C-terminal to the third YWTD repeat of the second YWTD/EGF domain in LRP5, while W504C is located between the third and the fourth YWTD repeats of the second YWTD/EGF domain in LRP5. Using LRP5-related proteins, such as the low-density lipoprotein receptor (LDLR) and nidogen as reference models, a homology model of LRP5 suggested that the observed mutations may affect the molecular interactions of LRP5 and so lead to the observed OPPG phenotypes.

Hypoxic-ischemic brain injury in the neonatal rat model: relationship between lesion size at early MR imaging and irreversible infarction.

BACKGROUND AND PURPOSE: By using a neonatal rat hypoxia-ischemia (HI) model, we studied the relationship between lesion volume-measured by diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) at an early time point-and irreversible infarct volume. We also evaluated the optimal apparent diffusion coefficient (ADC) threshold that provides the best correlation with irreversible infarct size. MATERIALS AND METHODS: Twenty-three neonatal rats underwent right common carotid artery ligation and hypoxia. MR imaging was performed 1-2 hours post-HI by using DWI and T2WI and at day 4 post-HI by using T2WI. Lesion volumes relative to whole brain (%LV) were measured on ADC maps by using different relative ADC thresholds 60%-80% of mean contralateral ADC and T2WI. Pearson correlation and multiple linear regression analysis were used to study the relationships between ln(%LV) at MR imaging and %LV at histopathology. RESULTS: At 1-2 hours post-HI, all lesion volume measurements on DWI were significantly correlated with the infarct volume on histopathology, with the best correlation attained at the 80% ADC threshold (r = 0.738; P < .001). The estimated regression formula was %LV on histopathology = 20.60 + 3.33 ln(%LV on 80% ADC threshold) (adjusted R(2) = 0.523; P < .001). Lesion volume at 1-2 hours post-HI tended to underestimate the final infarct volume. CONCLUSION: Early post-HI MR imaging by using DWI correlates moderately well with the size of irreversible infarct, especially when measured by using a relative ADC threshold of 80% mean contralateral ADC.

Strong association of HLA-DR3/DRw9 heterozygosity with early-onset insulin-dependent diabetes mellitus in Chinese.

Studies of Caucasian and Japanese patients with insulin-dependent diabetes mellitus (IDDM) have shown that heterozygosity for certain HLA-DR antigens confers a high risk of developing the disease. The HLA antigens of 75 Chinese patients and 100 Chinese controls in Hong Kong were studied to investigate the role of HLA-DR heterozygosity in Chinese individuals. Some of the patients and controls were also tested for allotypic variation in the complement components C2, C4, and BF. Three alleles, Aw33, B17, and DR3, had increased frequencies in patients compared with controls and frequently occurred together in the same phenotype, which suggested their existence as a haplotype. There were no statistically significant differences in complement allotype frequencies between patients and controls, although the C4B null allele seemed to be associated with Aw33, B17, and DR3. No other HLA-DR antigen appeared to be associated with IDDM. However, when the patients were separated on the basis of age at onset, the frequency of DR3/DRw9 heterozygosity was markedly increased in patients presenting in the first decade of life, but there was no increase in patients presenting at greater than 20 yr of age. DRw9 is strongly associated with autoimmune disease in Chinese, whereas DR3 is not. We suggest that the major IDDM susceptibility locus in Chinese is associated with HLA-DR3 and that patients with HLA-DR3 and HLA-DRw9 have an added predisposition to autoimmune disease and therefore develop IDDM earlier than patients without DRw9.

Mechanisms of Sertoli cell insulin-like growth factor (IGF)-binding protein-3 regulation by IGF-I and adenosine 3',5'-monophosphate.

FSH, which stimulates cAMP in the Sertoli cell, markedly lowers the concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) in Sertoli cell-conditioned medium; in contrast, insulin-like growth factor-I (IGF-I) increases BP-3 expression. In this study, the mechanisms controlling the contrasting effects of cAMP and IGF-I were investigated. The abundance of BP-3 mRNA was dramatically lowered by (Bu)2cAMP, but was unaffected by IGF-I. Analyzed by ligand blot of conditioned medium, coincubation of (Bu)2cAMP and IGF-I largely eliminated the increase observed with IGF-I alone. Based on the following evidence, the effect of IGF-I appeared to be solely related to the capacity of IGF-I to interact directly with BP-3. 1) Insulin at micromolar concentrations failed to increase BP-3 abundance despite documentation by affinity cross-linking that insulin displaced [125I]IGF-I from the IGF-I receptor. 2) A synthetic IGF-I analog, [Leu24,1-62]IGF-I, which has reduced binding affinity for rat IGF-I receptor but displays high affinity for rat Sertoli cell-conditioned medium BPs, increased BP-3 abundance. 3) A synthetic IGF-I analog, B-chain mutant, which has reduced affinity for rat Sertoli cell BPs but displays normal affinity for the rat IGF-I receptor, failed to increase BP-3 abundance. 4) Human recombinant glycosylated [125I]BP-3 when added to cultured Sertoli cells was preserved in the medium when IGF-I or analogs with BP-3 affinity were present. 5) IGF-I, in dose-responsive manner, both retarded the disappearance from the medium of exogenously added human recombinant nonglycosylated BP-3 and decreased the amount of membrane-associated BP-3. These results indicate that whereas cAMP lowers BP-3 abundance in medium, most likely by markedly decreasing synthesis, IGF-I increases BP-3 accumulation by retarding its clearance by the Sertoli cell.

Glucocorticoid regulation of an insulin-like growth factor-binding protein-4 protease produced by a rat neuronal cell line.

Insulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in distinct regions in the rodent brain from the perinatal period into adulthood and is postulated to modulate the action of the insulin-like growth factors (IGFs) in vivo. This study was initiated to examine the regulation of IGF-binding protein-4 (IGFBP-4) in B104 cells, a rat neuronal cell line in which IGFBP-4 is the predominant secreted IGFBP. Exposure of B104 monolayer cultures to dexamethasone reduced native IGFBP-4 abundance to less than 10% of that in control medium by 48 h. Immunoblots showed that the decline in intact 24-kilodalton IGFBP-4 was accompanied by an increase in a 16-kilodalton immunoreactive fragment. In addition, IGFBP-4 proteolytic activity in medium was increased after exposure of the cells to dexamethasone. The protease was calcium dependent and appeared to be of the serine protease class, because activity could be inhibited by phenylmethylsulfonylfluoride and aprotinin, but not antipain, leupeptin, or pepstatin. Although the proteolytically modified IGFBP-4 retained the ability to bind IGFs, the affinities were approximately 13- and 20-fold lower for IGF-I and IGF-II, respectively. These data indicate that B104 cells produce an IGFBP-4 protease that is regulated by glucocorticoids. The actions of this protease reduce the affinity of IGFBP-4 for the IGFs without abolishing binding. Because both the IGFs and glucocorticoids have important roles in brain development, it is possible that some glucocorticoid actions in the brain could be mediated by proteolysis of IGFBP-4, which, in turn, would alter IGF action.

Insulin-like growth factor-I (IGF-I) enhanced proteolysis of IGF-binding protein-4 in conditioned medium from primary cultures of human decidua: independence from IGF receptor binding.

Previous studies demonstrated that human decidual cells release insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-2, and a 24-kilodalton (kDa) IGFBP in culture. The accumulation of 24-kDa IGFBP, as assessed by ligand blot analysis, decreased when the cells were exposed to IGF-I, but the mechanism was not explored. In the present study, we observed that the IGF-I-mediated decrease in IGFBP-4 accumulation could be explained by increased IGFBP-4 proteolysis. Analysis by IGFBP-4 immunoblotting demonstrated a decline in 24-kDa IGFBP-4 accompanied by a marked increase in a 17- to 18.5-kDa IGFBP-4 fragment(s). In addition, when medium from IGF-I-treated cells was incubated with rat IGFBP-4, the decrease in IGFBP-4 was inhibited by chelators of divalent cations and inhibitors of serine proteases. IGF-I enhancement of IGFBP-4 proteolysis occurs independent of the type I IGF receptor. [Leu24,1-62]IGF-I, an analog with reduced receptor affinity, mimicked the effect of native IGF-I in cell culture. Additionally, alpha-IR3, a monoclonal antibody to the type I IGF receptor, did not block the effect of IGF-I. When IGF-I was incubated with medium from control cells, there was a marked decrease in 24-kDa IGFBP-4 levels and a concomitant increase in levels of a 17- to 18.5-kDa fragment(s), suggesting that IGFBP-4 complexed with IGF-I is more susceptible to proteolysis than IGFBP-4 alone. Together, these findings suggest a novel mechanism for regulation of IGF-I action in the decidua.

Characterization of an insulin-like growth factor binding protein (IGFBP-4) produced by the B104 rat neuronal cell line: chemical and biological properties and differential synthesis by sublines.

A previous report from our laboratory described an approximately 30 kilodalton (kDa) insulin-like growth factor binding protein (IGFBP) that inhibited the binding of insulin-like growth factor I (IGF-I) by its receptor and was secreted by a subline of the B104 rat neuronal cell line. To better understand the biology of this IGFBP, it was purified from media conditioned by these B104 cells, and the chemical and biological properties of the protein were examined. The IGFBP existed as a 24 kDa form and a 28 kDa form when the conditioned media were analyzed by ligand blot. Deglycosylation studies indicated the 28 kDa species was the N-linked glycosylated form of the 24 kDa IGFBP. Multiple forms at both mol wts were found using two-dimensional electrophoresis, suggesting that there were posttranslational modifications in addition to glycosylation. The amino acid sequence of the 12 amino-terminal residues was identical to that of rat IGFBP-4. Increased synthesis of IGFBP-4 by the subline contrasted with neglible production by other B104 cells. Blot hybridization with rat IGFBP-4 complementary DNA showed differential expression of a 2.6 kilobase transcript among B104 cell lines that correlated with quantities of IGFBP-4 secreted in media. The difference persisted even when the cells were xenografted into athymic nude mice. Purified IGFBP-4 inhibited the binding of [125I]IGF-I by its receptor and blunted stimulation of [3H]thymidine incorporation by IGF-I. These findings suggest a role for IGFBP-4 in neural cell function and indicate the B104 cell lines may be a useful model for further examination of IGFBP-4 biology.

Long term pulsatile growth hormone (GH)-releasing hormone therapy in children with GH deficiency.

We treated seven GH-deficient children with 3-hourly 1 microgram/kg sc pulses of GHRH-(1-44) for 6 months and 2 micrograms/kg.pulse for another 6 months. Four patients had a serum GH response to iv GHRH before treatment, and an additional patient responded to iv GHRH after 1 month of pulsatile sc GHRH administration. The mean cumulative growth velocity increased from a pretreatment mean of 2.7 +/- 0.2 (+/- SE) to 8.4 +/- 2.5 and 5.4 +/- 0.7 cm/yr after 2 months and 1 yr of treatment, respectively. Low dose pulsatile GHRH therapy was effective in promoting growth in five of seven children, with height gain ranging from 4.4-7.5 cm at the end of 1 yr's therapy. Only one of the two patients who did not respond to GHRH had an improvement in linear growth when they were subsequently treated with synthetic GH. The other patient, a 16.5-yr-old pubertal girl who had both satisfactory GH and somatomedin-C responses during GHRH therapy, did not respond to either GHRH or, later, synthetic GH. The pretreatment serum GH response to iv GHRH, the serum somatomedin-C concentrations, and the peak serum GH response during sc GHRH therapy were not reliable predictors of clinical response.

Perinatal hypoxia-/ischemia-induced endothelin-1 mRNA in astrocyte-like and endothelial cells.

Under pathological conditions in the adult CNS, such as ischemia, subarachnoid hemorrhage and Alzheimer's disease, endothelin (ET)-1- and -3-like immunoreactivities are elevated in astrocytes of the injured adult brain. However, it is not clear whether this is due to increased synthesis or increased binding of ET-1. Further, it is not known whether ET-1 expression is altered in the perinatal brain after cerebral hypoxia/ischemia (H/I). Here, we determined the sites of ET-1 expression in perinatal mouse brain after H/I injury by in situ hybridization using a probe specific for the ET-1 gene. Astrocyte-like cells, which do not normally express ET-1 mRNA, showed high levels of ET-1 mRNA expression. Endothelial cells of the capillaries and small vessels also showed an increased level of ET-1 mRNA. Our data suggest that ET-1 mRNA levels in the astrocyte-like cells and vascular endothelial cells are dynamically regulated by ischemia and may participate in perinatal ischemia-related neural damage.

Expression of insulin-like growth factor binding protein-4 (IGFBP-4) by rat neural cells--comparison to other IGFBPs.

We recently isolated and characterized the 24 kDa and N-glycosylated 28 kDa insulin-like growth factor binding protein-4 (rIGFBP-4) from the B104s rat neuronal cell line (Endocrinology, 129 (1991) 1009-1115). To examine the prevalence of IGFBP-4 secretion by cells of neural origin, we assessed the expression of IGFBP-4 in different neural cell types using ligand blotting, immunoblotting and blot hybridization with relevant cDNAs. A specific IGFBP-4 antibody raised against a synthetic 20 amino acid peptide was used for immunologic recognition. In all the neural cells tested (B104s, C6 astrocytoma, primary neonatal astrocytes and primary fetal neurons), IGFBP-4 was definitively identified by immunoblotting. Blot hybridization using a rat cDNA probe revealed expression of IGFBP-4 mRNA transcripts by all these cells. Using a combination of the same techniques, expression of IGFBP-1, -2, and -3 were also examined. The B104s cells secreted primarily IGFBP-4; C6 cells secreted predominantly IGFBP-3 and small amount of IGFBP-4; both primary neonatal astrocytes and fetal neurons secreted IGFBP-2 as the major IGFBP accompanied by a small quantity of IGFBP-4. IGFBP-1 was not identified in any of the cell media. When probed with the respective IGFBP cDNAs, the mRNA abundance generally reflected the media IGFBP content. The expression of IGFBP-4 mRNA in vivo was examined as well and compared to that of IGFBP-1 and IGFBP-2. Transcripts for both IGFBP-2 and IGFBP-4 were found in all gross anatomical divisions of the rat brain from embryonic day 15 until adulthood, whereas IGFBP-1 was not detected at any time. IGFBP-4 mRNA tended to be more abundant at the youngest ages whereas IGFBP-2 increased during development. These data indicate that IGFBP-4 is produce by a variety of neural cell types and suggest that it may play a role in brain development.

Clinical and electrophysiological features in Chinese patients with Kennedy's disease.

Kennedy's disease is a X-linked neuromuscular disorder caused by an expanded trinucleotide repeat in the androgen receptor gene. To ascertain the clinical diagnosis of Kennedy's disease in a Chinese population, we used a rapid, accurate PCR-based sizing method for the CAG repeat allelotype. The clinical and electrophysiological features of affected patients are described. The CAG repeats ranged from 43 to 53 and were inversely correlated with the age of onset (r = -0.63; P < 0.005).

The effect of 3 years of recombinant growth hormone therapy on glucose metabolism in short Chinese children with beta-thalassemia major.

Growth retardation and diabetes mellitus are common in children and adolescents with beta-thalassemia major despite hypertransfusion regimen and iron chelation therapy. The purpose of this study was to investigate the effects of growth hormone (GH) treatment on glucose metabolism in children with beta-thalassemia major. GH therapy for 3 years improved the height SD scores of eight short prepubertal Chinese children with beta-thalassemia major from -2.15 +/- 0.90 to -1.14 +/- 0.78 (paired t-test, p = 0.01) without excessive advancement in bone age (ABA/CA = 0.95 +/- 0.27). There was no deleterious effect on glucose metabolism with no change in fasting blood sugar, serum fructosamine, fasting and stimulated insulin to intravenous glucose infusion (sum of 1+3 min insulin, In 1+3'; incremental insulin 0-10 min area above fasting concentrations, deltaInAUC0-10'; ratio of incremental 0-10 min insulin area above fasting concentrations over glucose area above fasting concentrations, delta0-10'AUCIn/G; ratio of incremental 0-10 min insulin over peak glucose above basal 0-10 min, delta0-10'InAUC/deltaGPeak), and glucose disappearance coefficient (Kg). Short term GH therapy improves the height of children with beta-thalassemia major but the effect of treatment on final height still needs to be determined.

Epidemiology of diabetes mellitus in children in Hong Kong: the Hong Kong childhood diabetes register.

OBJECTIVES: To establish a registry for Chinese children with onset of type 1 (insulin dependent) diabetes mellitus before 15 years of age and to determine the incidence of childhood onset type 1 diabetes mellitus in Chinese children in Hong Kong. RESEARCH DESIGN AND METHODS: A registry was established in 1997 to collect childhood diabetes cases retrospectively from all districts in Hong Kong. The study included all newly diagnosed cases of diabetes with onset < 15 yr of age from 1st January 1984 to 31 December 1996. Primary ascertainment was based on review of medical records at all regional public hospitals in Hong Kong and survey of all the registered practitioners in Hong Kong. The secondary source of validation was made impractical, if not impossible, because of the recent implementation of the Personal Data Privacy Ordinance in Hong Kong. RESULTS: A total of 255 diabetic cases were identified, 227 type 1 diabetes mellitus (218 were Chinese), 18 type 2 diabetes mellitus and 11 secondary diabetes. 246 patients were Chinese and 9 non-Chinese. The age-standardized incidence of type 1 and type 2 diabetes mellitus in southern Chinese children in Hong Kong was 1.4/100,000/yr and 0.1/100,000/yr respectively for children < 15 yr of age during the study period. The incidence rates for type 1 diabetes were 0.9, 1.5 and 1.7 per 100,000/yr for 0-4 years, 5 to 9 years and 10 to 14 years age-groups respectively. The incidence for males was 1.2/100,000/yr and for females 1.7/100,000/yr. A significant increase in the incidence was demonstrated during the study period by simple linear regression (slope 0.14/100,000/year, r2 = 0.73, p = 0.0002) CONCLUSIONS: A diabetic registry is established in Hong Kong. This study documents a very low incidence rate of childhood type 1 diabetes mellitus in southern Chinese children in Hong Kong and we have seen an increasing incidence of the disease in the past 13 years.

The effect of platyspondyly and pubertal growth spurt on the stature of patients with beta-thalassaemia major.

OBJECTIVE: To study the effect of the body proportion and pubertal growth spurt on the stature of children with beta-thalassaemia major. METHODS: The height, sitting height, upper to lower segment (U:L) ratio and pubertal development were determined in 71 Chinese children (38 girls and 33 boys) with beta-thalassaemia. The growth patterns of 20 patients with complete growth data between 3 years and final height, were analyzed according to whether they underwent a pubertal growth spurt or not. RESULTS: 27% of the boys and 32% of the girls had a height below the 3rd percentile. About 60% of all the children had a U:L ratio below the 10th percentile for age. Abnormal body proportion was found in patients with or without growth retardation. 34% of the 41 children over the age of 14 years underwent spontaneous puberty. In 28 patients over the age of 16 years, a growth spurt was observed in 46% of the children during spontaneous or induced puberty. The retrospective analysis showed that the height deviation from the mean in adulthood was significantly higher in patients without pubertal growth acceleration than in those with a growth spurt (x = -11.8 cm, s = 7.6 cm vs x = -4.4 cm, s = 4.4 cm; P = 0.02). CONCLUSIONS: An abnormal U:L ratio was commonly observed in patients with beta-thalassaemia major and may be one factor contributing to the short stature of these patients. Abnormal puberty was present in a significant proportion of children and the lack of a pubertal growth spurt was found to be detrimental to adult height.

Phaeochromocytoma in children.

Phaeochromocytoma is a rare disease in childhood with a subtle and wide range of clinical presentations. We report two confirmed cases and one potential case of phaeochromocytoma, each belonging to a different disease spectrum or syndromal disorder, namely sporadic phaeochromocytoma, von Hippel-Lindau disease, and multiple endocrine neoplasia type 2a. Knowledge of the molecular basis of the condition helps to make the diagnosis. Affected individuals and their family members should be screened for any associated syndromal disorders that can carry a substantial degree of morbidity and mortality.