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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 government-led 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.

Objective: To evaluate potential risk factors, presenting symptoms, management, and outcomes of intracranial haemorrhage in Chinese children with immune thrombocytopenia managed in a regional hospital., Design: Retrospective case series., Setting: A regional hospital in Hong Kong., Patients: All paediatric patients with immune thrombocytopenia complicated by intracranial haemorrhage in the period January 1996 to December 2009., Results: Nine episodes of intracranial haemorrhage were reported in eight patients (aged 0.9 to 19 years) with immune thrombocytopenia; three of the patients had acute immune thrombocytopenia and the other five had chronic immune thrombocytopenia. Intracranial haemorrhage occurred as early as the initial presentation with immune thrombocytopenia (n=2) and as late as up to 5 years after the diagnosis. The median platelet count at the time of intracranial haemorrhage was 12 x 10(9) /L (<10 x 10(9) /L [n=4]; 10-20 x 10(9) /L [n=2]; >20 x 10(9) /L [n=3]). The bleeding was considered spontaneous in six episodes, while head trauma (n=2) and vascular malformation (n=1) were identified in three patients with mild-to-moderate thrombocytopenia (42-82 x 10(9) /L) at the time of the bleed. Headache and mucosal bleeding were the commonest presenting symptoms (n=5). All patients received multimodal treatment after diagnosis of intracranial haemorrhage, and included platelet transfusion (n=8), intravenous immunoglobulin (n=6), methylprednisolone (n=4), and splenectomy (n=4); three individuals underwent neurosurgical interventions. One (11%) patient died of posterior fossa bleeding and one (11%) had neurological sequelae. All survivors achieved remission of their immune thrombocytopenia with a median follow-up of 5.3 years., Conclusion: Intracranial haemorrhage can occur anytime during the course of immune thrombocytopenia. A high index of suspicion for intracranial haemorrhage should be maintained during follow-up, as favourable outcomes can be achieved after early and vigorous interventions.

Objectives: The aims of this study were to evaluate the specificity of a non-draining hepatobiliary scintigraphy (HBS) for biliary atresia (BA) in preterm and full-term babies, to verify the relationship between non-draining scan and higher levels of direct bilirubin and to find an objective criterion to guide the time in performing HBS., Methods: A total of 175 infants (113 males and 62 females, median age of 45 days) with 181 HBS performed in Tuen Mun Hospital between January 1998 and May 2010 were retrospectively analysed. A 'non-draining' scan was defined as one showing no excretion of radiolabelled tracer into the small bowel 24 h after injection. The disease category, epidemiological and laboratory data were compared between infants having non-draining and draining scans. In addition, the predictive value of a negative scan for BA was compared between preterm and full-term infants., Results: Twenty infants (11.4%) were surgically confirmed to have BA. A non-draining scan was found to be 100% sensitive for BA, and the specificity was 96% and 78% among full-term infants and preterm infants, respectively. The mean direct bilirubin values of infants with BA and intrahepatic cholestasis were 141.9 and 111.3 μmol/L, respectively, which were significantly higher than 67.2 μmol/L seen in infants with draining scans. This analysis shows that using direct bilirubin ≥63 μmol/L as an objective criterion in guiding the time to perform HBS is most cost-effective., Conclusion: Our data supported that using direct bilirubin ≥63 μmol/L as an objective criterion in guiding the time to perform HBS will avoid unnecessary scans., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Aim: Inborn errors of metabolism (IEM) are an unpopular and difficult subject and most clinicians are unfamiliar with them. Although chemical pathologists have a long-standing practice in advising test strategy and result interpretation especially from primary care, such consultations are usually informal, unstructured and those related to IEM are infrequently requested. This study aims to provide a formal electronic consultation service and to apply tandem mass spectrometry-based dried blood spot metabolic screening (DBSM) as a rapid first-line test for patients suspected of IEM., Methods: DBSM and a chemical pathology consultation were ordered through the hospital computer terminals. DBSM detected 29 metabolic disorders. The clinical data and metabolic results for the 12-month period were reviewed., Results: There were 279 consultations of which 209 were initiated by paediatricians and 70 by adult physicians. The main reasons for consultation were developmental delay, neurological abnormalities, unexplained biochemical abnormalities and monitoring of patients with IEM. There were 158 DBSM requests. One positive case of isovaleric acidaemia was detected., Conclusions: All high-risk paediatric patients should have a DBSM and a timely electronic chemical pathology consultation as a rapid and cost-effective first-line screening. Provision of a visible, accessible and helpful consultation service enables professional reimbursement.

OBJECTIVES. To clarify the use of ultrasonography by determining the frequency of developmental dysplasia of the hip among breech-presented Chinese neonates in Hong Kong. DESIGN. Prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. All breech-presented Chinese neonates born during January 2008 to June 2009 were included (except premature neonates). They were examined clinically from birth till the age of 1 year. Ultrasound of the hips was performed at the age of 2 weeks, and X-ray of the pelvis at the age of 1 year. RESULTS. A total of 209 breech-presented neonates were born during the study period; 110 neonates completed all necessary investigations and follow-up. Among the latter, there were three neonates with developmental dysplasia of the hip warranting treatment, which amounted to a frequency of 2.7%. CONCLUSION. Developmental dysplasia of the hip among breech-presented Chinese babies is only slightly less common than in corresponding populations in other regions in the world. Since early diagnosis is important, ultrasonography screening in high-risk cases such as those with breech presentation may be useful.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the most common fatty acid oxidation defects that cause sudden unexpected deaths in infants. The death attributed to VLCAD deficiency can be prevented by early diagnosis with expanded newborn screening using tandem mass spectrometry. A favorable outcome can be achieved with early diagnosis and prompt treatment. However, such newborn screening has not yet been available in Hong Kong. We report a 2-month-old boy who succumbed 5 hours after admission with the diagnosis of VLCAD deficiency confirmed by genetic analysis performed after death. The patient was compound heterozygous for a novel splicing mutation ACADVL NM&#95;000018.2:c.277+2T>G; NC&#95;000017.10:g.7123997T>G and a known disease-causing mutation ACADVL NM&#95;000018.2:c.388&#95;390del; NP&#95;000009.1: p.Glu130del. Family screening was performed for at-risk siblings. The rapid downhill course of the patient clearly illustrates the need of newborn screening for early diagnosis. Our patient was asymptomatic before metabolic decompensation. However, once metabolic decompensation occurred, rapid deterioration and death followed, which obviated the opportunity to diagnose and treat. The only way to save these patients' lives and improve their outcome is early diagnosis and appropriate treatment. Therefore, we strongly urge the implementation of newborn screening using tandem mass spectrometry for VLCAD deficiency and other highly treatable inborn errors of metabolism in Hong Kong.

Objective: To investigate whether requests for standard paediatric electroencephalograms accord with guideline recommendations, subsequent changes in clinical management according to reported results, and extent to which the service meets waiting time targets., Design: Case series., Setting: Regional hospital, Hong Kong., Patients: All patients aged less than 18 years who underwent electroencephalography between December 2009 and February 2010., Main Outcome Measures: Appropriateness of the electroencephalogram request and the impact of its findings on clinical management., Results: A total of 109 patients were recruited, but requests for standard electroencephalograms were considered 'inappropriate' with respect to guidelines in 44% of the patients, of which 50% were made to diagnose 'funny turns'. The standard electroencephalogram contributed to the diagnosis or management in only 28% of patients. In all of the latter, the request for an electroencephalogram had been appropriate. Nonspecialists made referrals for 86% of the patients. Inadequate information was provided in 66% of the requests. Standard electroencephalograms were performed within guideline targets, the wait being less than 4 weeks in 95% of requests., Conclusion: An effective electroencephalogram service was being provided, though abuses were common. These were mainly because of misconceptions regarding the role and limitations of standard electroencephalograms. Through an educative, non-confrontational approach, and with time to explain guideline recommendations to clinicians, sustainable change in practice could be achieved so as to benefit patients, clinicians, and service provision.

Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele [p.Phe352Cys; p.Val368Ile] were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0+C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of [p.Phe352Cys; p.Val368Ile] among Hong Kong Chinese was 0.104, similar to Japanese data, and [p.Phe352Cys] has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE.

This is a retrospective review of the clinico-radiological features and neurological outcomes of reversible posterior leukoencephalopathy syndrome episodes in Chinese cancer children receiving chemotherapy in a regional hospital in Hong Kong from 1998 to 2008. Five children (3 males and 2 females) with a mean age of 7 years were identified, four of whom had acute lymphoblastic leukaemia and one had a central nervous system germ cell tumour. Presenting symptoms included seizures (100%), altered mental function (100%), headache (40%), and visual disturbance (60%). The mean systolic blood pressure at presentation was 158 mm Hg. Approximately 80% had typical radiological features of reversible posterior leukoencephalopathy syndrome. All showed complete recovery after the acute stage, but one subsequently developed epilepsy. Two patients ultimately died of refractory malignant disease. Two others were followed up for a mean of 6 years, and remained neurologically normal. This report was the first case review documenting reversible posterior leukoencephalopathy syndrome in Chinese cancer children. The clinico-radiological features and neurological outcomes were similar to those reported in western series. Early recognition of the syndrome is important to facilitate appropriate treatment. The central nervous system damage may not be reversible and thus long-term follow-up is warranted.

A Chinese adolescent girl presented with secondary amenorrhea. During follow-up, she gradually developed Cushingoid features and virilization. After a series of endocrine investigations, including urinary steroid profiling, a diagnosis of adrenocortical carcinoma was made. The treatment and prognosis of the disease are discussed.

Aim: To describe the disease burden, clinical pattern and outcome of influenza-related hospitalisations in children., Methods: This is a retrospective study carried out in a regional hospital in Hong Kong. Children hospitalised with established diagnosis of influenza infection from January to June of 2005 were studied. Length of hospitalisation, demographic characteristics, symptoms, clinical diagnosis and complications of influenza infection were analysed., Results: Influenza A infection accounted for 93.5% of these hospitalisations. Children less than 5 years of age comprised 70% of admission. Highest rate of admission occurred in May and April. One fourth of emergency admission during the study period and over 70% in the peak season was a result of influenza-related illness. Underlying medical disease was observed in 14.6% of children. Mean duration of hospitalisation was 3.0 days. Fever was the commonest presenting symptoms. Fever lasting for 7 days or more was observed in one-fifth of patients. Respiratory tract diseases (upper and lower) were the most frequent non-neurological diagnosis. Febrile convulsion was the complication observed in 27.6% of admission. One patient died as a result of acute necrotising encephalopathy., Conclusion: Influenza contributed to heavy health-care burden. Mortality was rare but did occur. Hospitalisations occurred in both healthy children and those with underlying chronic illness. Young children played an important role in such hospitalisations. Means to prevent influenza-associated morbidity and mortality especially among young children are needed.

Purpose: To compare the performance of polymerase chain reaction versus conventional methods (cell culture and direct immunofluorescent assay) in diagnosing neonatal chlamydial conjunctivitis and their correlations to the severity of conjunctivitis., Methods: Consecutive cases of neonatal conjunctivitis were recruited over a year. Both eyes were clinically graded according to the severity of conjunctivitis and investigated using the three aforementioned chlamydial tests. Neonatal chlamydial conjunctivitis was assumed if one of these three tests was positive and there was clinical improvement after treatment. Sensitivity and specificity of each of the tests were analyzed., Results: Three hundred sixty-eight sets of chlamydial tests were done for 184 neonates. The percentage of positive results was 93.8% and 71.9% for polymerase chain reaction and conventional methods, respectively. Using positive results in either cell culture or direct immunofluorescent assay as a standard to diagnose neonatal chlamydial conjunctivitis, the sensitivity and specificity of polymerase chain reaction were 92.0% and 97.7%, respectively. If we used polymerase chain reaction as a standard, the sensitivity and specificity of cell culture were 73.3% and 99.7%, respectively. A discrepancy was noted in the number of positive results between polymerase chain reaction and conventional methods in milder disease., Conclusions: Polymerase chain reaction might have a higher sensitivity and similar specificity in diagnosing neonatal chlamydial conjunctivitis compared to conventional methods, and it has an additional advantage as a diagnostic tool in mild disease.

Ornithine transcarbamylase deficiency is the commonest urea cycle disorder which is transmitted in X-linked inheritance. It is mainly characterized in males by acute encephalopathy and hyperammonaemia with fatal outcomes in both classical neonatal and late-onset types. We report a 3-year-old healthy Hong Kong Chinese boy who presented with acute encephalopathy and coma after three days of gastroenteritis. He had no focal neurological deficit and brain CT imaging was normal. His plasma ammonia (54 micromol/L) and glutamine (747 micromol/L) concentrations were normal. The only biochemical abnormalities detected were marked orotic aciduria (700 micromol/mmol creatinine) and elevated urinary uracil. He regained consciousness spontaneously after three days under intensive care with parenteral fluid therapy. He recovered completely without any neurological deficits. Five months after discharge, urinary uracil concentration remained elevated despite normalized orotic acid concentration. Finally, ornithine transcarbamylase deficiency was diagnosed by DNA analysis. A missense mutation of arginine-to-glutamine substitution on amino acid 277 (p.R277Q) was revealed to be a late-onset mutant. Our case strengthens the argument that in any child with coma or acute encephalopathy of undetermined cause, genetic analysis of the OTC gene and the measurement of urinary uracil concentration remain the most reliable indicators of late-onset OTCD during acute and even quiescent phases. Existing neonatal screening programmes for inheritable metabolic disorders fail to detect late-onset variants. Therefore, a high clinical suspicion is a key to correct and timely diagnosis, especially in those patients with atypical presentations.

Objectives: Using polymerase chain reactions, this study aimed to evaluate the incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong and explore any association between such conjunctivitis and nasopharyngeal colonisation with Chlamydia trachomatis., Design: Prospective epidemiological study., Setting: Regional hospital, Hong Kong., Patients: Consecutive patients with neonatal conjunctivitis presenting to our hospital were recruited from May 2004 to April 2005 inclusive. Both eyes were investigated separately for Chlamydia trachomatis by polymerase chain reaction, direct immunofluorescent assay, and cell culture by two assigned ophthalmologists. Neonates diagnosed to have ocular Chlamydia trachomatis infection were subjected to additional nasopharyngeal investigations. Complete sets of ocular and nasopharyngeal investigations were also undertaken 1 week after oral erythromycin treatment to confirm complete eradication of Chlamydia trachomatis., Results: Of 192 patients with neonatal conjunctivitis, 24 were diagnosed to have chlamydial conjunctivitis. Fifteen of them had nasopharyngeal colonisation with Chlamydia trachomatis. Among the 20 neonatal chlamydial conjunctivitis patients that completed the follow-up study, one suffered treatment failure. None had clinically diagnosed systemic Chlamydia trachomatis infection 3 months after oral erythromycin., Conclusions: The incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong was 4 in 1000 live births, of whom 63% had nasopharyngeal presence of Chlamydia trachomatis. Owing to the high rate of nasopharyngeal isolation and possibility of treatment failure, post-treatment ocular and nasopharyngeal polymerase chain reaction testing for Chlamydia trachomatis may be considered to confirm complete eradication.

We report two cases of newborn death and two cases of near-miss newborn death. One neonate was strangled to death after delivery in the hospital and one died from lethal congenital malformations. The third was found on the verge of death after being abandoned in a dumpster. The fourth was rescued from the toilet bowl by the mother's boyfriend while the mother was in a state of panic. In the three cases where the infants' maternal identities were known, the women were all primiparous and aged 22, 13, and 17 years. The paternity was extramarital, incestuous, and concealed, respectively. Denial or concealment of pregnancy was present in all cases, but none of the women had any overt psychiatric manifestations at the time of delivery. Neonaticide and newborn abandonment are closely associated with denial of pregnancy, and are serious forms of childhood victimisation. Their occurrence in Hong Kong is poorly understood and no representative figures are available. A concerted effort among the health care, social work, and judicial professionals is needed to define the scope of the problem and devise preventive measures.

Objective: To review the bacteriological causes and clinical features of acute neonatal conjunctivitis in a local paediatric centre., Design: Retrospective review., Setting: Paediatric unit of a regional hospital, Hong Kong., Patients: All neonates who presented to Tuen Mun Hospital from 1 January 1996 to 31 December 2002 with persistent eye discharge and a positive eye swab culture., Main Outcome Measures: Clinical features of neonates with chlamydial and non-chlamydial conjunctivitis., Results: Of 90 neonates with positive eye swab or conjunctival scraping cultures, Chlamydia trachomatis was the second most common (n=19, 21%) cause of acute neonatal conjunctivitis after Staphylococcus aureus (n=32, 36%). All of the neonates with chlamydial conjunctivitis were delivered vaginally: two of them had concomitant chlamydial pneumonia. Neisseria gonorrhoeae conjunctivitis was rare (n=1, 1%). None of the mothers of neonates with Chlamydia had any history of sexually transmitted disease. The timing of presentation, gestational age, birth weight, and sex of the neonates did not suggest a risk of chlamydial infection. Nonetheless haemorrhagic eye discharge had a specificity of 100% and positive predictive value of 100% for chlamydial infection. There were no adverse ophthalmological consequences or complications of pyloric stenosis in any neonate following treatment with oral erythromycin., Conclusions: Haemorrhagic eye discharge is a highly specific sign of neonatal chlamydial conjunctivitis. Early and prompt treatment with oral erythromycin is safe and effective.

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.

An interferometric sensing scheme using a multimode fiber and a self-pumped phase conjugator is proposed. The self-pumped phase conjugator corrects the distortion due to mode scrambling in the fiber and responds to any uniform optical phase change caused by environmental factors. A temperature sensor based on the proposed scheme is used to demonstrate the feasibility of the scheme.