Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

Review on the screening of urine glucose for early diagnosis of type 2 diabetes mellitus in school children and adolescents with obesity in Hong Kong.

OBJECTIVES: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. METHODS: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. RESULTS: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. CONCLUSIONS: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA1c can be explored to improve program effectiveness.

24 h Activity Guidelines in Children and Adolescents: A Prevalence Survey in Asia-Pacific Cities.

This study aimed to examine the prevalence of adherence to 24 h activity guidelines in children and adolescents from Asia-Pacific cities. In 1139 children aged 5-18 years, moderate-to-vigorous physical activity (MVPA), screen viewing time (SVT), sleep duration, child weight, height, sex, and age were parent-reported. Descriptive statistics were used to assess the number of guidelines met, and prevalence of adherence to activity guidelines by city and child sex. Prevalence of meeting all three 24 h activity guidelines was low across all countries (1.8-10.3%) (p < 0.05). Children from Thiruvananthapuram, India had the highest [10.3% (95% CI: 6.0-17.0)], while those from Tokyo, Japan had the lowest prevalence [1.8% (95% CI: 0.5-7.0)] of meeting all three guidelines. The highest prevalence of meeting individual MVPA, SVT and sleep guidelines was found in India [67.5% (95% CI: 58.8-75.1)], Kelaniya, Sri Lanka [63.2% (95% CI: 58.7-67.4)] and Kowloon, Hong Kong [59.4% (95% CI: 51.1-65.3)], respectively. Overall, a higher prevalence of boys met all three guidelines, compared to girls [5.9% (95% CI: 4.1-8.1) vs. 4.7% (3.1-6.6), p = 0.32]. The prevalence of adhering to all three activity guidelines was low in all five participating cities, with a higher proportion of boys meeting all guidelines.

Diabetic ketoacidosis in children with new-onset type 1 diabetes mellitus: demographics, risk factors and outcome: an 11 year review in Hong Kong.

OBJECTIVES: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1D). The aim of this study is to analyze the incidence, clinical characteristics, management and outcome of children presenting with DKA in new-onset T1D from 2008 to 2018 in Hong Kong. METHODS: Data was extracted from the Hong Kong Childhood Diabetes Registry. All subjects less than 18 years with newly diagnosed T1D from 1 January 2008 to 31 December 2018 managed in the public hospitals were included. Information on demographics, laboratory parameters, DKA-related complications and management were analyzed. RESULTS: In the study period, there were 556 children with newly diagnosed T1D in our registry and 43.3% presented with DKA. The crude incidence rate of new-onset T1D with DKA was 1.79 per 100,000 persons/year (CI: 1.56-2.04). Subjects presenting with DKA were younger (9.5 ± 4.5 vs. 10.5 ± 4.4, p=0.01) and had shorter duration of symptoms (4.2 ± 5.9 days vs. 10.6 ± 17.1 days, p<0.01). Regarding management, up to 12.4% were given insulin boluses and 82.6% were started on insulin infusion 1 h after fluid resuscitation. The rate of cerebral edema was 0.8% and there was no mortality. CONCLUSIONS: Younger age and shorter duration of symptoms were associated with DKA in new-onset T1D. Despite availability of international guidelines, there was inconsistency in acute DKA management. These call for a need to raise public awareness on childhood diabetes as well as standardization of practice in management of pediatric DKA in Hong Kong.

Incidence and clinical characteristics of pediatric-onset type 2 diabetes in Hong Kong: The Hong Kong childhood diabetes registry 2008 to 2017.

OBJECTIVE: With increasing prevalence of childhood obesity worldwide, the incidence of pediatric-onset type 2 diabetes (T2D) is also increasing in many countries. We aim to analyze the time trend and incidence of T2D in children in Hong Kong from 2008 to 2017, and to characterize clinical characteristics at diagnosis. METHODS: Data were retrieved from the Hong Kong Childhood Diabetes Registry. All children with T2D diagnosed at the age of less than 18 years from January 1, 2008 to December 31, 2017 and managed in the public health care system were included in this study. RESULTS: In the incident years of 2008-2017 period, 391 children were diagnosed with T2D. The crude incidence rate was 3.42 per 100,000 persons/year [95% confidence interval (CI) 3.08-3.76], which was much higher than that in last registry of 1.27 per 100,000 persons/year in 1997-2007 (P < 0.001).Most children (76%) were asymptomatic and were diagnosed by routine screening. At presentation, a significant proportion presented with co-morbidities including fatty liver (37.9%), dyslipidaemia (35.3%), hypertension (22.5%), and microalbuminuria (12.8%). CONCLUSIONS: The incidence of T2D in children has increased significantly in Hong Kong. Most of them were asymptomatic and picked up on routine health screening. Yet, comorbidities were commonly identified at diagnosis.

Increasing incidence of type 1 diabetes among Hong Kong children and adolescents: The Hong Kong Childhood Diabetes Registry 2008 to 2017.

OBJECTIVE: The incidence of childhood-onset type 1 diabetes (T1D) has been reported to be rising but there is also evidence that it has been attenuated in recent years. We described the time trends and the incidence of T1D in children in Hong Kong from 2008 to 2017 and compared with the previous local registry in 1997 to 2007. METHODS: Data were extracted from the Hong Kong Childhood Diabetes Registry, which was established in 2016. It consists of a retrospective registry (including all childhood diabetes diagnosed in 2008 to 2015) and a prospective registry (including all T1D children diagnosed from 2016 onwards). All T1D children diagnosed at the age of less than 18 years from 1 January 2008 to 31 December 2017 and managed in the public system were included in this study. RESULTS: For the incident years in the 2008 to 2017 period, a total of 498 children with T1D was identified. The crude incidence rate was 4.3 per 100 000 person/year (95% confidence interval 3.96-4.72), which was much higher than the last registry of 2.2 per 100 000 persons/year. Using general linear model, the increment is statistically significant (P = .02). When compared to the last registry, the rate of increment had attenuated, with annual increment in crude incidence in the two periods for T1D <15 years changing from 4.3% to 3.5% (P = .02). CONCLUSIONS: The incidence of T1D children increased significantly in the past two decades in Hong Kong, but the rate of increase had attenuated in recent years.

Identifying the need for a multidisciplinary approach for early recognition of mucopolysaccharidosis VI (MPS VI).

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is caused by deficient activity of the enzyme, N-acetylgalactosamine-4-sulfatase, resulting in impaired degradation of the glycosaminoglycan dermatan sulfate. Patients experience a range of manifestations including joint contractures, short stature, dysostosis multiplex, coarse facial features, decreased pulmonary function, cardiac abnormalities, corneal clouding and shortened life span. Recently, clinicians from institutions in the Asia-Pacific region met to discuss the occurrence and implications of delayed diagnosis and misdiagnosis of MPS VI in the patients they have managed. Eighteen patients (44% female) were diagnosed. The most common sign presented by the patients was bone deformities in 11 patients (65%). Delays to diagnosis occurred due to the lack of or distance to diagnostic facilities for four patients (31%), alternative diagnoses for two patients (15%), and misleading symptoms experienced by two patients (15%). Several patients experienced manifestations that were subtler than would be expected and were subsequently overlooked. Several cases highlighted the unique challenges associated with diagnosing MPS VI from the perspective of different specialties and provide insights into how these patients initially present, which may help to elucidate strategies to improve the diagnosis of MPS VI.

Cardiopulmonary morbidity of streptococcal infections in a PICU.

AIM: The streptococci are important bacteria that cause serious childhood infections. We investigated cardiopulmonary morbidity associated with streptococcal infection and pediatric intensive care unit (PICU) admission. METHODS: A retrospective study between 2002 and 2013 of all children with a laboratory isolation of streptococcus. RESULTS: There were 40 (2.3%) PICU patients with streptococcal isolations including Streptococcus pyogenes (Group A streptococcus, GAS, n = 7), Streptococcus agalactiae (Group B streptococcus, GBS, n = 5), Streptococcus pneumoniae (SP, n = 20), alpha-hemolytic (n = 4), beta-hemolytic (n = 2) and gama-hemolytic (n = 2) streptococci. Comparing among GAS, GBS and SP, respiratory isolates were more likely positive for GAS or SP (P = 0.033), whereas cerebrospinal fluid was more likely positive for GBS (P = 0.002). All GAS and GBS, and the majority of SP (90%) were sensitive to penicillin. All SP specimens were sensitive to cefotaxime and vancomycin. These infections were associated with high PICU mortality of 43%, 20% and 25%, respectively. Isolation of streptococci was associated with a 30% mortality and high rates of need for mechanical ventilatory and inotropic supports. Patients with GAS, SP or any streptococcal isolation had relative risks [95% confidence interval (CI), P value] of PICU deaths of 7.5 (CI 3.1-18.1, P < 0.0001), 4.5 (CI 2.0-9.8, P < 0.0002) and 5.7 (CI 3.4-9.5, P < 0.0001), respectively. In SP, older children had significantly higher prevalence of premorbid conditions such as malignancy, mental retardation/cerebral palsy ± seizure disorders, chromosomal or genetic disorders (P = 0.003) than children <5 years of age. Serotypes were available for some of these specimens that included 19A, 6B, 3 and 6C. There were four SP deaths with multiorgan system failure and hemolytic uremic syndrome (two 19A and two serotype 3). CONCLUSIONS: Severe streptococcal infections are associated with significant morbidity and mortality despite treatment with systemic antibiotics and intensive care unit support. GAS and SP affect the lungs of children, whereas GBS more likely causes meningitis in infants. The expanded coverage of newer polyvalent pneumococcal vaccines can probably prevent infections by serotypes 19A, 19F, 6B and 3.

Typical or atypical pneumonia and severe acute respiratory symptoms in PICU.

BACKGROUND AND AIMS: Mycoplasma pneumoniae (MP) is a common childhood pathogen associated with atypical pneumonia (AP). It is often a mild disease and seldom results in paediatric intensive care (PICU) admission. In 2003, World Health Organization (WHO) coined the word SARS (severe acute respiratory syndrome) in patients with severe acute respiratory symptoms (sars) for an outbreak of AP in Hong Kong due to a novel coronavirus. In 2012, another outbreak of coronavirus AP occurred in the Middle East. Confusing case definitions such as MERS (Middle East respiratory syndrome) and SARI (severe acute respiratory infections) were coined. This paper aims to present a case of MP with sars, ARDS, pneumonia and pleural effusion during the MERS epidemics, and review the incidence and mortality of severe AP with MP. METHODS: We presented a case of MP with sars, acute respiratory distress syndrome (ARDS), pneumonia and pleural effusion during the MERS epidemics, and performed a literature review on the incidence and mortality of severe AP with MP requiring PICU care. RESULTS: In early 2013, an 11-year-old girl presented with sars, ARDS (acute respiratory distress syndrome), right-sided pneumonia and pleural effusion. She was treated with multiple antibiotics. Streptococcus pneumoniae was not isolated in this girl with 'typical' pneumonia by symptomatology and chest radiography, but tracheal aspirate identified MP instead. The respiratory equations are computed with PaO2 /FiO2 consistent with severe lung injury. Literature on the incidence and mortality of severe AP with MP requiring PICU care is reviewed. Six, 165 and 293 articles were found when PubMed (a service of the U.S. National Library of Medicine) was searched for the terms 'mycoplasma' and 'ICU', 'mycoplasma' and 'mortality', and 'mycoplasma' and 'severe'. Mortality and PICU admission associated with MP is general low and rarely reported. Experimental and clinical studies have suggested that the pathogenesis of lung injuries in MP infection is associated with a cell-mediated immune reaction, and high responsiveness to corticosteroid therapy has been reported especially for severe disease. Management of severe mycoplasma infection in the PICU includes general cardiopulmonary support and specific antimicrobial treatment. Macrolide resistance genotypes have been detected. CONCLUSION: We urge health organizations to refrain from the temptation of coining unnecessary new terminology to describe essentially the same conditions each and every time when outbreaks of AP occur.

Overcoming the barriers to diagnosis of Morquio A syndrome.

BACKGROUND: Morquio A syndrome is an autosomal recessive lysosomal storage disease often resulting in life-threatening complications. Early recognition and proficient diagnosis is imperative to facilitate prompt treatment and prevention of clinical complications. METHODS: Experts in Asia Pacific reviewed medical records focusing on presenting signs and symptoms leading to a diagnosis of Morquio A syndrome. RESULTS: Eighteen patients (77% female) had a mean (median; min, max) age of 77.1 (42.0; 0.0, 540.0) months at symptom onset, 78.9 (42.0; 4.5, 540.0) months at presentation and 113.8 (60.0; 7.0, 540.0) months at diagnosis. Orthopedic surgeons and pediatricians were most frequently consulted pre-diagnosis while clinical geneticists/metabolic specialists most frequently made the diagnosis. Delayed diagnoses were due to atypical symptoms for 5 patients (28%), while 4 patients (22%) experienced each of subtle symptoms, symptoms commonly associated with other diseases, or false-negative urine glycosaminoglycan analysis. Two patients (11%) each experienced overgrowth within the first year of life. Two patients with Morquio A syndrome (11%) were diagnosed with craniosynostosis and 1 (6%) for each of Legg-Calvé-Perthes disease, Leri-Weill syndrome, and pseudoachondroplasia. Early radiographic features of Morquio A syndrome led to more efficient diagnosis. CONCLUSIONS: Increased awareness of clinical symptomology overlapping with Morquio A syndrome is essential. Clinicians encountering patients with certain skeletal dysplasia should consider Morquio A syndrome in their differential diagnosis. Atypical or subtle symptoms should not eliminate Morquio A syndrome from the differential diagnosis, especially for patients who may have non-classical phenotype of Morquio A syndrome.