Public and Healthcare Provider Receptivity toward the Retention of Dried Blood Spot Cards and Their Usage for Extended Genetic Testing in Hong Kong

Dried blood spot (DBS) cards from newborn screening (NBS) programs represent a wealth of biological data. They can be stored easily for a long time, have the potential to support medical and public health research, and have secondary usages such as quality assurance and forensics, making it the ideal candidate for bio-banking. However, worldwide policies vary with regard to the duration of storage of DBS cards and how it can be used. Recent advances in genomics have also made it possible to perform extended genetic testing on DBS cards in the newborn period to diagnose both actionable and non-actionable childhood and adult diseases. Both storage and secondary uses of DBS cards raise many ethical, clinical, and social questions. The openness of the key stakeholders, namely, parents and healthcare providers (HCPs), to store the DBS cards, and for what duration and purposes, and to extended genetic testing is largely dependent on local cultural–social-specific factors. The study objective is to assess the parents’ and HCPs’ awareness and receptivity toward DBS retention, its secondary usage, and extended genetic testing. A cross-sectional, self-administrated survey was adopted at three hospitals, out of which two were public hospitals with maternity services, between June and December 2022. In total, 452 parents and 107 HCPs completed and returned the survey. Overall, both HCPs and parents were largely knowledgeable about the potential benefits of DBS card storage for a prolonged period and its secondary uses, and they supported extended genetic testing. Knowledge gaps were found in respondents with a lower education level who did not know that a DBS card could be stored for an extended period (p p = 0.033), and could aid public health research, and future policy implementation (p = 0.030). Main concerns with regard to DBS card storage related to potential privacy breaches and anonymity (Parents 70%, HCPs 60%). More parents, compared to HCPs, believed that storing DBS cards for secondary research does not lead to a reciprocal benefit to the child (p p < 0.001). Our findings report positive support from both parents and HCPs toward the extended retention of DBS cards for secondary usage and for extended genetic testing. However, more efforts to raise awareness need to be undertaken in addition to addressing the ethical concerns of both parents and HCPs to pave the way forward toward policy-making for DBS bio-banking and extended genetic testing in Hong Kong

Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of SLC25A13 by the copy number variant calling algorithm. Genetic second-tier tests were performed for 1.8% of a total of 22,883 NBS samples. The false positive rate for these six conditions after the NGS second-tier test was only 0.017%, and two cases of citrullinemia type II would have been missed as false negatives if only biochemical first-tier testing was performed. The confirmed true positive cases were citrullinemia type II (n = 2) and systemic primary carnitine deficiency (n = 1). The false positives were later confirmed to be carrier of citrullinemia type II (n = 2), carrier of glutaric acidemia type I (n = 1) and carrier of systemic primary carnitine deficiency (n = 1). There were no false negatives reported. The incorporation of a second-tier genetic screening test by NGS greatly enhanced our program’s performance with 5-working days turn-around time maintained as before. In addition, early genetic information is available at the time of recall to facilitate better clinical management and genetic counseling

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

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib