Objective: Evaluation of the prevalence of different thyroid disorders and co-morbidities in children and adolescents with Down syndrome (DS). Methodology: Retrospective review of medical records from a tertiary referral centre in Hong Kong from 2002 to 2017. Prevalence of different thyroid disorders and associations with co-morbidities were calculated. Results: Among the 157 patients enrolled in analysis, impaired thyroid function was found in 58 ( 36.9%) patients. The most common form of thyroid-related disorder was subclinical hypothyroidism. Of note, 4.5% of them had oscillating thyroid diseases. Antithyroid antibody testing was done in 19% of the patients. Haematological malignancies were significantly associated with development of any thyroid diseases (p=0.026). Fifty percent of DS patients were shown to be affected by thyroid abnormalities by 22.9 years. Conclusion: Thyroid abnormalities are very common among children with DS. Anti-thyroid antibody testing is indicated in older children to delineate the risk of development or persistence of thyroid diseases. Consensus is needed to standardise the time points of thyroid function evaluation especially during early stages of life.

The Joint Committee on Universal Newborn Hearing Screening ( UNHS) was formed to ensure the effective implementation of UNHS in Hong Kong and to achieve effective communication among various services in Hospital Authority and Department of Health. Meetings with multidisciplinary professionals had been conducted during the years of 2013 and 2014.

Since the coronavirus disease 2019 (COVID-19) outbreak in late December 2019, and escalation of the public hospital infectious disease outbreak response level to the highest "emergency" level three days after two COVID-19 cases were diagnosed on 22 January 2020, all public hospitals implemented a series of isolation policies, rescheduled clinical services and mobilised resources to support frontline clinical staff. This article reviewed these multi-level policies adopted in the Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, which have ensured that the healthcare system was not overwhelmed and frontline staff was not over-stressed and infected.

Background: Citrin deficiency is a treatable inborn error of amino acid metabolism, which commonly presents as neonatal cholestasis in East Asians. However, with sequencing-based methods, in some patients only one monoallelic pathogenic variant in SLC25A13 is found for this autosomal recessive condition. Gross deletions in SLC25A13 are reported, but their detection often requires specialised techniques which may not be readily available.

Introduction: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. Methods: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. Results: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. Conclusion: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a governmentled initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

INTRODUCTION There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism. METHODS Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry. RESULTS In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression. CONCLUSIONS Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.

Objective: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population.Design: Case series.Setting: Five public hospitals in Hong Kong.Patients: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011.Main outcome measures: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification.Results: Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhoea. Baseline and post human chorionic go nadotropin stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5 alpha-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A/-related sex reversal, and persistent Mullerian duct syndrome.Conclusions: Our findings suggest that 5a-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

Disorders of sex development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. In 46, XY DSD, the genotype is XY, but the external genitalia is incompletely virilised, ambiguous, or completely female. The objectives of this prospective study are to evaluate the testicular Sertoli and Leydig cell functions, to establish the genetic basis and to determine the relative prevalence of etiologies in Chinese patients with 46,XY DSD in Hong Kong. All patients with 46,XY DSD (either new or known) presented to five paediatric departments in Hong Kong from July 2009 till June 2011 were recruited. They were assessed by paediatric endocrinologists. Comprehensive evaluation of testicular and adrenal functions was performed using serum hormonal assays and urine steroid profiling. Based on the hormonal results, mutational analyses of the candidate genes by polymerase chain reaction and direct DNA sequencing were conducted to delineate the genetic basis of the etiologies. Sixty-five patients (54 male and 11 female) with 46,XY DSD were recruited. Their age ranged from birth to 27 years. Sixty-one (94%) patients presented with ambiguous external genitalia, two presented with delayed puberty and one each with primary amenorrhoea and inguinal hernia. Definitive diagnoses were made in 25 (38%) patients. Eleven (17%) patients had 5-alpha reductase 2 deficiency. Androgen insensitivity was confirmed by genetic analysis in eight (12%) patients. There was one patient with each of the following etiologies: Swyer syndrome, SF-1 mutation, Frasier syndrome, cholesterol side-chain cleavage deficiency, persistent Mullerian duct syndrome and mixed gonadal dysgenesis. Genetic basis of the etiologies was delineated in 23 (35%) patients. A total of 10 novel mutations were identified. The longest follow up period was 27 years, none of the patients requested change of gender sex so far. In conclusion, 46,XY DSD is a heterogeneous group with diverse etiologies. Although 5-alpha reductase 2 deficiency is believed to be rare, it is not uncommon in Hong Kong.

BACKGROUND 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD. METHODS We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years. RESULTS Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically. CONCLUSIONS 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.

Capecitabine is an orally administered pro-drug of 5-fluorouracil that confers superior disease-free survival and presumably has a more favourable side-effect profile. Here we report on a patient who developed acute necrotising pancreatitis and very high triglyceride levels as well as hand-foot syndrome after receiving capecitabine for colonic cancer. Increased awareness of this potential side-effect and close monitoring of lipid levels may be warranted, especially in patients who have other conditions predisposing them to severe secondary hyperlipidaemia when using this drug.

Aim The upper reference limit of thyroid-stimulating hormone (TSH) is critical for defining patients with subclinical hypothyroidism, a condition which carries a higher risk of progression to overt hypothyroidism and adverse cardiovascular events. Yet, there is a lack of consensus on its absolute value, and data in non-pregnant adult Chinese are lacking.Methods Apparently healthy and drug-free local adult Chinese were recruited by completing health questionnaires. Their serum samples were tested for TSH, free thyroxine (FT4), thyroglobulin antibody and thyroid peroxidase antibody levels. After excluding subjects with thyroid antibodies, the TSH level was log-transformed, and the reference limits were defined as mean +/- 1.96SD. The 2.5th and 97.5th percentiles of FT4 were also calculated.Results Serum samples from 212 subjects were used in this study. 51 subjects were seropositive to thyroglobulin antibody, 31 were seropositive to thyroid peroxidase antibody, and 27 were seropositive to both. The reference intervals after excluding subjects seropositive to thyroid antibodies were: TSH: 0.68-3.70 mIU/l; FT4: 13.5-21.3 pmol/l (male) and 12.6-19.7 pmol/l (female). Including subjects with thyroid antibodies only minimally changed the reference intervals of these hormones.Conclusion The authors have set up the reference interval of TSH for the local population, and their findings also suggest that the importance of excluding subjects with thyroid antibodies in the reference population should not be overemphasised. Moreover, the international authorities should consider recommending percentile-equivalent action limits instead of an absolute cut-off on TSH for categorisation of different types of thyroid dysfunction.

Background: Congenital adrenal hyperplasia (CAN) caused by 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder due to mutation in the CYP21A2 gene.Objective: To elucidate the genetic basis of 21-hydroxylase-deficient CAH in Hong Kong Chinese patients.Patients and methods: Mutational analysis of the CYP21A2 gene was performed on 35 Hong Kong Chinese patients with 21OHD using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).Results: The genetic findings of 21 male and 14 female patients are the following: c.293-13A/C > G (intron 2 splice site; 20 alleles), p.I172N (13), p.R356W (7), p.Q318X (4). A total of 20 mutant alleles contained gross deletion/conversion of all or part of the CYP21A2 gene. A novel mutation. c.1367delA (p.D456fs), was detected in one patient. One patient had only a heterozygous mutation detected. Out of 35 patients, 16 would have been incorrectly genotyped if either DNA sequencing or MLPA alone was used for molecular analysis.Conclusions: The frequency of various mutations in the studied patients differs from those reported in other Asian populations. Gross deletion/conversion accounts for nearly one-third of the genetic defects. Therefore, laboratories must include methods for detecting point mutations as well as gross deletions/conversions to avoid misinterpretation of genotype. Genotyping has increasingly been proven to be a useful tool for supplementing, if not replacing, hormonal profiling for the diagnosis of 21OHD. (C) 2011 Elsevier Inc. All rights reserved.

Conference Theme: Advances in Genetics and Genomics - Opportunities for the Asia-Pacific Region

Background: Urinary steroid profiling by GC or GC-MS are established clinical tools to complement other biochemical tests in the diagnosis and investigation of a wide range of adrenocortical disorders, but normative data on adults using the more specific GC-MS are lacking. our objective was to set up the reference intervals of commonly detected urinary steroid metabolites as well as marker metabolites seen in disease states.Method: Apparently healthy adult Chinese males and females were recruited by completing health questionnaires. A 24-h urine specimen was collected from all the participants for urinary steroid profiling by GC-MS in cyclic scan mode. The analyzer was calibrated by using authentic steroid standards. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were followed for setting up the reference intervals of various steroid metabolites. After outliers were excluded, the data were tested for the necessity to partition into sex-, menopausal status- and age-specific reference intervals.Results: 83 males and 89 females were recruited for the study. Necessity to partition into sex-specific reference intervals was demonstrated for almost all steroid metabolites. Menopausal status and age also had a significant impact on steroid metabolite excretion, making separate reference intervals necessary.Conclusions: We have set up the normative data on the levels of urinary steroid metabolite excretion in Chinese adults for future reference in patient management and research in steroid metabolism. (C) 2008 Elsevier Inc. All rights reserved.

Urolithiasis is all uncommon renal problem in paediatrics. Once identified, however, a thorough investigation Should be performed to look for the underlying cause. Children with renal stone may present as haematuria, recurrent abdominal pain and urinary tract infection. Since abdominal colic is a common reason for medical consultation, rare cause like renal stone call be easily overlooked. We reported all infant presented as recurrent abdominal pain and positive urine Culture. Subsequent work up revealed the diagnosis of Type A cystinuria.

AIM:Setting up reference intervals from the local service populations is one of the major responsibilities of clinical laboratories. Yet, this task is difficult to achieve because it is costly and time consuming when compared with validating reference intervals from assay manufacturers.METHODS:Following the recommendations of the International Federation of Clinical Chemistry, healthy local Chinese adults were recruited to set up reference intervals for common serum analytes. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were used for defining the reference limits.RESULTS:Data from 335 subjects were analysed. The reference intervals set up were broadly similar to those provided by the assay manufacturer, except for sodium and potassium. Glomerular filtration rate was estimated by the modification of diet in renal disease equation, with or without modification for Chinese. Body mass index had a significant impact on serum urate and alanine aminotransferase levels.CONCLUSION:Reference intervals of common serum analytes have been set up for the local Chinese population. A good example of quality laboratory service has also been set up to provide clinicians with reliable reference intervals that they can confidently rely on for the diagnosis and management of patients.