Draft genome sequencing of halotolerant bacterium Salinicola sp. DM10 unravels plant growth-promoting potentials.

In this study, strain DM10 was isolated from mangrove roots and characterized as a halotolerant plant growth-promoting bacterium. Strain DM10 exhibited the ability to solubilize phosphate, produce siderophore, show 1-aminocyclopropane-1-carboxylic acid deaminase activity, and hydrolyze starch. The rice plants subjected to a treatment of NaCl (200 mM) and inoculated with strain DM10 showed an improvement in the shoot length, root length, and dried weight, when compared to those exposed solely to saline treatment. The comprehensive genome sequencing of strain DM10 revealed a genome spanning of 4,171,745 bp, harboring 3626 protein coding sequences. Within its genome, strain DM10 possesses genes responsible for both salt-in and salt-out strategies, indicative of a robust genetic adaptation aimed at fostering salt tolerance. Additionally, the genome encodes genes involved in phosphate solubilization, such as the synthesis of gluconic acid, high-affinity phosphate transport systems, and alkaline phosphatase. In the genome of DM10, we identified the acdS gene, responsible for encoding 1-aminocyclopropane-1-carboxylate deaminase, as well as the amy1A gene, which encodes α-amylase. Furthermore, the genome of DM10 contains sequences associated with the iron (3+)-hydroxamate and iron uptake clusters, responsible for siderophore production. Such data provide a deep understanding of the mechanism employed by strain DM10 to combat osmotic and salinity stress, facilitate plant growth, and elucidate its molecular-level behaviors.

The institutional experience of the implementing 4DCT in NSCLC radiotherapy planning.

Background: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation. Materials and methods: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins. Results: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT. Conclusions: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.

Mobilizing morality: how caregivers in Vietnam handle the challenges of daily diabetes care.

BACKGROUND: As a chronic disease, type 2 diabetes (T2D) often involves long-term care obligations for patients' family members. Understanding the socially and culturally specific challenges that family caregivers face and how they cope with them is crucial in developing targeted and effective interventions to support both caregivers and patients with T2D. This research examined family caregiving for people with T2D living in rural northern Vietnam. Although there is a growing literature on family support in Vietnam, little is known about the personal experiences of family caregivers for people with T2D. This paper seeks to fill this gap revealing some of the challenges and coping strategies of family caregivers to people with T2D. METHODS: This qualitative study is based on ethnographic research using primarily semi-structured interviews with 21 caregivers to a person with T2D in Vietnam. The research was conducted in 2022 by a Vietnamese-Danish research team. Each interview was voice-recorded, transcribed verbatim and thematically coded. RESULTS: Four major challenges emerged from the analysis: physical health concerns, psychological exhaustion, economic burdens, and lack of support. Caregivers expressed motivation to overcome these challenges as they felt a deep sense of responsibility towards their family member with diabetes. The primary caregiver's sense of responsibility toward their family would often cause them not to share the burdens from caregiving with other family members to avoid burdening them as well. However, negative experiences from caregiving were decreased and positive feelings increased in the instances where caregiving was shared between multiple family members. CONCLUSION: While family members expressed motivation to take care of the patient because of moral obligations, some caregivers, specifically primary caregivers, did not want to burden other family members with care tasks and were reluctant to ask for assistance. For families who did share the caregiving tasks among several family members, some of the negative sentiments associated with caregiving were diminished. Having multiple members of a family forming a caregiving community thus motivated people in handling care challenges.

Determination of tacrolimus in human whole blood in kidney transplant recipients using a rapid and specific LC-MS/MS method.

OBJECTIVE: To develop and validate an LC-M/SMS method for the determination of tacrolimus in human whole blood. METHOD: The LC-MS/MS method for the determination of tacrolimus in whole blood was developed and validated according to the guidelines. Concentrations of TAC in 100 kidney transplant patients measured by LC-MS/MS were compared with CMIA using correlation analysis and Bland-Altman plots. RESULTS: The method had a total chromatographic run time of 5 min. The calibration curves were linear over the range of 0.5-100.0 ng/mL with a lower limit of quantification of 1 ng/mL. The intra- and interday accuracy was within the range of 93.3%-109.2% and 96.0%-108.4%, respectively, with precision ranging from 0.8 to 9.4%. The mean extraction recoveries of TAC ranged from 102.6 to 107.8%. The mean concentrations of TAC in whole blood of kidney transplant patients measured by the two assays were different at 1, 3 months and all time points (p < 0.001), but no significant difference was observed at 6 months (p = 0.094). The correlation of data was good with the correlation coefficients (r2 ) of 0.7581, 0.8811, 0.8777, and 0.8077, respectively. Passing-Bablok regression analysis demonstrated good correlations with r2 values higher than 0.88 between TAC levels measured by LC-MS/MS and CMIA. Using Bland-Altman plots yielded average biases of 1.29, 0.79, 0.11, and 0.65 ng/mL at 1, 3, and 6 months and all time points. CONCLUSION: The LC-MS/MS method was validated for the accurate determination of TAC in human whole blood. The comparison of tacrolimus concentrations measured by the LC-MS/MS with CMIA showed a good correlation and agreement of two methods, suggesting LC-MS/MS should be used routinely to monitor TAC concentrations in kidney transplant patients.

Anterolateral thigh adipofascial flap combined with skin paddle in three-dimension scalp reconstruction: A case report.

INTRODUCTION AND IMPORTANCE: Management of cranial and scalp defects is always challenging. Complication rates following cranioplasty are still high (10-40 %), including bone graft resorption, infection, and T-mesh implant exposure due to thinning of soft tissue (Yeap et al., 2019; Alkhaibary et al., 2020; Cho and Kang, 2017 [1-3]). CASE PRESENTATION: We present a case of a 38-year-old male with autologous bone graft resorption accompanied by thinning of the forehead skin. He underwent cranioplasty with titanium mesh (T-mesh) and scalp reconstruction with an anterolateral thigh (ALT) flap in a single-stage operation. A 2-component ALT flap was used: the skin paddle covered the scalp defect to reduce closure tension, and especially the adipofascial flap lining beneath the forehead skin to increase thickness. Postoperative results were great in terms of coverage function and aesthetics. CLINICAL DISCUSSION: The phenomenon of soft tissue thinning causing titanium mesh exposure is a common complication with a rate of 10-14 % (Yeap et al., 2019; Dong et al., 2020; Maqbool et al., 2018 [1, 4, 5]). Using adipofascial ALT flap as a sub-scalp filler material has many advantages over the latissimus dorsi (LD) flap to increase scalp thickness but still ensure aesthetics. CONCLUSION: The results suggest a new direction in using adipofascial ALT flap as filler material to increase scalp thickness to reduce T-mesh exposure following cranioplasty.

Techniques of inserting deep inferior epigastric perforator flap obliquely in immediate breast reconstruction after total mastectomy.

Objective: This study aimed to share the experience of inserting a deep inferior epigastric perforator (D.I.E.P) flap obliquely in immediate breast reconstruction after total mastectomy. Method: Forty patients underwent immediate breast reconstruction with flap D.I.E.P after total mastectomy. The flaps were placed obliquely, with the upper edge facing downward and inward. After being placed in the recipient region, parts of the flap at both ends were removed, the upper end was fixed into the II-III intercostal space next to the sternum, and the lower end was folded to create a projection of the lateral lower pole of the breast. The flap pedicle was anastomosed to the thoracodorsal vessels (TDVs) if the contralateral flap pedicle was used; conversely, the mammary vessels (IMVs) were used. Satisfaction with breast shape was assessed after 6 months using the BREAST-Q questionnaire. Results: A total of 37/40 flaps were well vascularized; 36/37 patients with a survival flap were interviewed, showing that the average BREAST-Q evaluation score of satisfaction with breast shape was 62.22 (51-78). The number of answers for satisfied and very satisfied with breast shape accounted for 94.44%. Conclusion: Inserting the D.I.E.P flap obliquely has the advantage of being easy to shape the breast contour, creating a moderate projection and symmetry to the opposite breast. The author suggested using the IMVs as the receiving vessels when using the pedicle of the flap on the ipsilateral side and the TDVs when the contralateral pedicle flap was used.

Frequencies and Association of CYP3A5 Polymorphism With Tacrolimus Concentration Among Renal Transplant Recipients in Vietnam.

BACKGROUND: This study aims to investigate the frequencies and association of CYP3A5 polymorphism with tacrolimus concentration among renal transplant recipients in Vietnam. METHODS: Sixty-eight kidney transplant recipients were included in this study from the department of nephrology and dialysis, Military Hospital 103. Blood samples were collected for monitoring of tacrolimus levels and determination of CYP3A5 genetic polymorphism. RESULTS: A total of 68 patients studied. The CYP3A5*3*3, CYP3A5*1*3, and CYP3A5*1*1 genotypes were detected in 48 (70.6%), 16 (23.5%), and 4 (5.9%), respectively. Tacrolimus concentrations were much lower in CYP3A5 expressors than in CYP3A5 nonexpressors on the first day, month 1, 3, 6, and 12 (5.98 ± 1.05 vs 6.57 ± 1.03, P = .03; 5.79 ± 1.13 vs 6.82 ± 1.05, P < .001; 4.76 ± 1.48 vs 6.73 ± 1.09, P < .001; 4.29 ± 1.64 vs 6.46 ± 1.23, P < .001; 4.20 ± 1.36 vs 6.04 ± 1.26, P < .001), respectively. Notably, the concentration/dose ratio in the CYP3A5 expressors was lower than in CYP3A5 nonexpressors at time points of follow up (P < .001). However, there were no significant differences in the age, sex, HLA mismatch, type of donors, acute rejection, and creatinine levels at time points between group of CYP3A5 expressors and those of CYP3A5 nonexpressors. CONCLUSION: In conclusion, this research indicated the significant association of CYP3A5 genetic polymorphism with daily dose and tacrolimus concentrations in renal transplant recipients. This study provided a closer step to individualize the dose of tacrolimus in renal transplant patients in Vietnam.

Augmentation Rhinoplasty in Cleft Lip Nasal Deformity Using Alloplastic Material and Autologous Cartilage.

Secondary cleft rhinoplasty typically requires large amounts of cartilage grafts for augmentation. The purpose of this study was to present our short-term experience with alloplastic implants in cleft rhinoplasty. This was a retrospective cohort study of cleft lip and palate patients treated with secondary rhinoplasty at Hanoi Medical University Hospital and Ruby Hospital between 2017 and 2020. All rhinoplasty procedures consisted of lower lateral cartilage repositioning, a dorsal augmentation with silicone implant, columellar strut implant or graft, and onlay tip grafts. Cartilage was obtained from the septum and concha, and no cartilage was harvested from the rib. The study outcomes included the Rhinoplasty Outcome Evaluation (ROE) survey, a modified Mortier scoring scale, 8 intranasal measures of symmetry, and 4 nasofacial measures of tip projection and nasal length. Changes in patient satisfaction and nasal esthetics were compared before and after surgery. A total of 38 patients were included in the final study sample, of whom 65.79% had unilateral clefts. The overall complication rate was 7.89%, and there were 2 cases of infection and 1 case of dorsal implant displacement. Following rhinoplasty, ROE satisfaction scores significantly increased (+39.36, P <0.01) and Mortier severity scores decreased (-3.06, P <0.01). Nostril symmetry nearly normalized in width, height, and inclination. Mean columellar deviation decreased from 8.82 to 2.08 degrees, and nasal projection increased as assessed on multiple analyses. Patients with bilateral clefts had similar improvements in ROE and Mortier scores. In our experience, synthetic implants simplified the correction of cleft nasal deformity and eliminated the need for costal cartilage. We found that our protocol produced acceptable and stable short-term clinical results without increasing the complication rate above what has been reported with autologous grafts.

Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants.

Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic ERCC8 (CS-A) or ERCC6 (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without photosensitivity, which delayed a clinical diagnosis for 16 years. By whole-exome sequencing we identified the two novel compound heterozygous ERCC8 variants c.370_371del (p.L124Efs*15) and c.484G>C (p.G162R). The causality of the ERCC8 variants, of which one results in a frameshift and the other affects the WD3 domain, was tested and confirmed by a rescue experiment investigating DNA repair in H2O2 treated patient fibroblasts. Structural modeling of the p.G162R variant indicates effects on protein-protein interaction. This case shows the importance to test for ERCC6 and ERCC8 variants even if patients do not present with a complete CS phenotype.

Genetic Etiology of Neonatal Diabetes Mellitus in Vietnamese Infants and Characteristics of Those With INS Gene Mutations.

Background: Neonatal diabetes mellitus (NDM) is a rare (1:90,000 newborns) but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. Dominantly-acting insulin (INS) gene mutations cause permanent NDM through single amino acid changes in the protein sequence leading to protein misfolding, which is retained within the endoplasmic reticulum (ER), causing ER stress and ß-cell apoptosis. Over 90 dominantly-acting INS gene mutations have been identified in individuals with permanent NDM. Patients and Methods: The study included 70 infants diagnosed with NDM in the first year of life between May 2008 and May 2021 at the Vietnam National Children's Hospital. Sequencing analysis of all the genes known to cause NDM was performed at the Exeter Genomic Laboratory, UK. Clinical characteristics, molecular genetics, and annual data relating to glycemic control (HbA1c) and severe hypoglycemia of those with INS mutations were collected. The main outcomes of interest were HbA1c, daily insulin dose, growth, and cognitive/motor development. Results: Fifty-five of 70 infants (78.5%) with NDM harbored a mutation in a known disease-causing gene and of these, 10 had six different de novo heterozygous INS mutations. Mean gestational age was 38.1 ± 2.5 weeks and mean birth weight was 2.8 ± 0.5 g. They presented with NDM at 20 ± 17 weeks of age; 6/10 had diabetic ketoacidosis with pH 7.13 ± 0.26; plasma glucose level 32.6 ± 14.3 mmol/l and HbA1C 81 ± 15% mmol/mol. After 5.5 ± 4.8 years of insulin treatment, 9/10 have normal development with a developmental quotient of 80-100% and HbA1C 64 ± 7.3 mmol/mol, 9/10 have normal height, weight, and BMI on follow-up. Conclusions: We report a series of Vietnamese NDM cases with dominant INS mutations. INS mutations are the third commonest cause of permanent NDM. We recommend screening of the INS gene in all children diagnosed with diabetes in the first year of life.

Comparison of the Welfare of Gestation Sows Raised in Different Production Systems in North Vietnam.

Intensification and complexity of pig production systems may require different strategies for animal welfare improvement. We aimed to identify welfare issues of gestation sows and areas for improvement by comparing four production systems, including the smallholder pen-based system (SPS: 26 farms), smallholder stall-based system (SSS:14 farms), semi-intensive stall-based system (SES: 15 farms), and intensive stall-based system (ISS: 10 farms). Ten significant animal-based measures in the Welfare Quality® protocol were used for welfare assessment at the individual level. Stall-housed sows in SES and ISS faced more welfare problems where sows presented a higher prevalence of poor body condition (P < 0.001), wounds on body (P = 0.003), fear of humans (P < 0.001), and stereotypies (P < 0.001) than pen-housed sows in the SPS. Sows in the SPS presented the highest prevalence of panting (P < 0.001). Welfare improvement should be focused on minimizing the adverse effects of hot weather on sows in the SPS and SSS and redesigning a more welfare-friendly housing system that prevents sows from the risk of wounds on body and enables them to perform motivated behaviors in the SES and ISS.

Closing the Type 1 Diabetes gap in South-East Asia through government partnership working with non-government organisations.

This will be the first publication of Type 1 diabetes(T1D) outcomes in five low-middle-income countries (LMICs)-Laos, Malaysia, Vietnam, Cambodia and Myanmar in the Southeast Asia (SEA) region. The information obtained has been possible due to partnership programmes of non-government organisationAction4Diabetes (A4D) with defined local hospitalsthrough a Memorandum of Understandingsigned with the governments in SEAthat guarantees ongoing supplies of free insulin, blood glucose meter supplies, HbA1c tests and hospital emergency funds. PARTICIPANTS: Between 2020 and 2021, 383 children and young people with T1D who were active in the A4D supported programmes were reviewed including information on health coverage, multidisciplinary team management, diabetic ketoacidosis (DKA) on admission and insulin regimen. RESULTS: Mean HbA1c between 2020 and 2021 for patients in these LMICs arereported for the first time. The average glycaemic index in the five SEAcountries reviewed between 2020 and 2021 were high at 83 mmol/mol (9.7%). CONCLUSIONS: Government partnership working with non-government organisationsto support T1D from diagnosis to adulthood are the first steps to closing thegaps in many LMICs. Further epidemiological studies are needed to identify the glycaemic outcomes and DKA rates on admission for many of these countries.

Existential vulnerability: an ethnographic study of everyday lives with diabetes in Vietnam.

This article asks: how can the concept of existential vulnerability help us to comprehend the human impact of chronic disease? Across the globe, the prevalence of chronic health conditions is rising dramatically, with wide-ranging consequences for human lives. Taking type II diabetes in northern Vietnam as its ethnographic case, this study explores how chronic health conditions are woven into everyday lives, altering subjectivities and social relations. Applying the notion of existential vulnerability as its analytical prism, the article explores three different dimensions of vulnerability: physical, emotional, and social. The analysis highlights the importance of a focus on social connectedness for comprehending the everyday impact of chronic disease and for the development of health care interventions in this domain.

Molecular Genetics, Clinical Characteristics, and Treatment Outcomes of KATP-Channel Neonatal Diabetes Mellitus in Vietnam National Children's Hospital.

Background: Neonatal diabetes mellitus (NDM) is defined as insulin-requiring persistent hyperglycemia occurring within the first 6 months of life, which can result from mutations in at least 25 different genes. Activating heterozygous mutations in genes encoding either of the subunits of the ATP-sensitive K+ channel (KATP channel; KCNJ11 or ABCC8) of the pancreatic beta cell are the most common cause of permanent NDM and the second most common cause of transient NDM. Patients with NDM caused by KATP channel mutations are sensitive to sulfonylurea (SU) treatment; therefore, their clinical management can be improved by replacing insulin with oral agents. Patients and Methods: Seventy patients were diagnosed with NDM between May 2008 and May 2021 at Vietnam National Children's Hospital, and molecular genetic testing for all genes known to cause NDM was performed at the Exeter Genomic Laboratory, UK. Patients with ABCC8 or KCNJ11 mutations were transferred from insulin to oral SU. Clinical characteristics, molecular genetics, and annual data relating to glycemic control, SU dose, severe hypoglycemia, and side effects were collected. The main outcomes of interest were SU dose, SU failure (defined as permanent reintroduction of daily insulin), and glycemic control (HbA1c). Results: Fifty-four of 70 patients (77%) with NDM harbored a genetic mutation and of these; 27 (50%) had activating heterozygous mutations in ABCC8 or KCNJ11. A total of 21 pathogenic mutations were identified in the 27 patients, including 13 mutations in ABCC8 and 8 mutations in KCNJ11. Overall, 51% had low birth weight (below 3rd percentile), 23 (85%) were diagnosed before 3 months of age, and 23 (85%) presented with diabetic ketoacidosis. At diagnosis, clinical and biochemical findings (mean ± SD) were pH 7.16 ± 0.16; HCO3- , 7.9 ± 7.4 mmol/L; BE, -17.9 ± 9.1 mmol/L; HbA1C, 7.98% ± 2.93%; blood glucose, 36.2 ± 12.3 mmol/L; and C-peptide median, 0.09 (range, 0-1.61 nmol/l). Twenty-six patients were successfully transferred from insulin to SU therapy. In the remaining case, remission of diabetes occurred prior to transfer. Glycemic control on SU treatment was better than on insulin treatment: HbA1c and blood glucose level decreased from 7.58% ± 4.63% and 19.04 ± 14.09 mmol/L when treated with insulin to 5.8 ± 0.94% and 6.87 ± 3.46 mmol/L when treated with SU, respectively. Conclusions: This is the first case series of NDM patients with ABCC8/KCNJ11 mutations reported in Vietnam. SU is safe in the short term for these patients and more effective than insulin therapy, consistent with all studies to date. This is relevant for populations where access to and cost of insulin are problematic, reinforcing the importance of genetic testing for NDM.

Patterns of behavioral risk factors for non-communicable diseases in Vietnam: A narrative scoping review.

This review describes both magnitude and patterns of major behavioral risk factors for NCDs. Positive changes in tobacco use were identified, though this is far to meet the established expectation. Harmful alcohol consumption was reported, especially for males. Only small proportion of the population consumed an adequate amount of fruits and vegetables daily. Average salt intake was approximately doubled, in comparison to WHO's recommendations. Physical activity has shifted gradually negatively, but future trends are unpredictable. An organized surveillance system should be developed initially with adequate tools and public resources to maintain and ensure sustainability over time.

We All Have a Role to Play: Redressing Inequities for Children Living with CAH and Other Chronic Health Conditions of Childhood in Resource-Poor Settings.

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN's activities for children living with CAH in the Asia Pacific. The seven stages of the KTA action cycle inform a systematic examination of comprehensive, collaborative, sustained actions to address a complex health challenge. The KTA framework demonstrates the "how" of CLAN's approach to knowledge creation and exchange, and the centrality of community development to multisectoral collaborative action across a range of conditions, cultures and countries to redressing child health inequities. This includes a commitment to: affordable access to essential medicines and equipment; education, research and advocacy; optimisation of medical management; encouragement of family support groups; efforts to reduce financial burdens; and ethical, transparent program management as critical components of success. Improvements in quality of life and health outcomes are achievable for children living with CAH and other chronic health conditions in resource-poor settings. CLAN's strategic framework for action offers a model for those committed to #LeaveNoChildBehind.

Quality of life of older adults in nursing homes in Vietnam.

This study evaluated the quality of life of older adults in Vietnam. A survey was conducted on 291 old people at eight public and private nursing homes using cluster sampling. Quality of life was predicted by gender, duration of stay, center activities and community tangible support, and connection with family. Results were consistent across the four subscales of the Quality of Life Index. Quality of life of Vietnamese older adults depends not only on the quality of services provided by the nursing homes but also on family and community connections.

Late-Onset Ornithine Transcarbamylase Deficiency and Variable Phenotypes in Vietnamese Females With OTC Mutations.

Background: Ornithine transcarbamylase deficiency (OTCD) is an X- linked recessive disorder and the most common error of the urea cycle, caused by the mutations in the OTC gene. Due to X-inactivation, 15-20% of female carriers present symptoms of OTCD at late onset. Early diagnosis of OTCD by molecular analysis in females is highly desirable. The aim of the study was to identify the mutations in two unrelated Vietnamese girls suspected with OTCD and the carriers in their families for definitive diagnosis and proper counseling. Case Presentation: Two patients presented with an acute encephalopathy at the first admission. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase, elevated urinary orotic and uracil acid levels, and disorder of prothrombin time. Brain magnetic resonance imaging indicated cerebral edema. Based on the clinical and laboratory results, the two patients were diagnosed with urea cycle disorders. Therefore, the two patients were managed by stopping feeding, with infused glucose, l-carnitine, l-arginine, and sodium benzoate, and with hemofiltration. The two patients were alert and recovered with normal blood ammonia levels after 72 h of treatment. The family history of patient 1 showed that her brother died at 4 days of age due to a coma and dyspnea, while her parents were asymptomatic. Variable phenotypes were observed in three generations of the patient 2's family, including asymptomatic (mother), affected female adults dying at the first symptom (grandmother and aunt), and affected males dying in the first week of life (uncle, cousin, and siblings). Whole-exome sequencing showed two mutations in the OTC gene, including one novel missense mutation, c.365A>T, in the patient 1 and one previously reported splicing mutation, c.717+1G>A, in the patient 2. The two mutations are evaluated as likely pathogenic and pathogenic, respectively, according to the recommendations of the American College of Medical Genetics and Genomics (ACMG). Genetic analyses in the families indicated the mothers were heterozygous. Conclusion: Clinical, biochemical, and molecular findings accurately diagnosed the two patients with late-onset OTCD. Our results explained the genetic causes and proposed the risk in the patients' families, which could be useful for genetic counseling and monitoring in prenatal diagnosis.

A novel frameshift PHKA2 mutation in a family with glycogen storage disease type IXa: A first report in Vietnam and review of literature.

BACKGROUND: Glycogen storage diseases (GSDs) are clinically and genetically heterogeneous disorders. Overlapping features between liver GSDs are a major challenge in the clinical diagnosis of them. Genetic testing can provide an early and accurate diagnosis of patients suspected with GSDs. CASE PRESENTATION: In this study, we report two siblings born to healthy, non-consanguineous Vietnamese parents with hepatomegaly. The proband presented with hepatomegaly, normal spleen, elevated transaminases, without hypoglycemia, normal lactate dehydrogenase and creatine kinase. Liver biopsy revealed degeneration and swollen hepatocytes, suggesting a diagnosis with GSDs. METHODS: Whole exome sequencing was applied to identify genetic variants in the proband. Variant validation and familial co-segregation analysis were examined using Sanger sequencing. RESULTS: A novel frameshift duplication mutation c.3308_3312dupATGTC (p.L1105Mfs*11) of the PHKA2 gene was identified in the proband and his elder brother at the hemizygous state. This mutation was inherited from their mother. Their father and younger brother were normal genotype. CONCLUSIONS: The two siblings were accurately diagnosed with GSD type XIa. This is the first case report of GSD type IXa in Vietnamese patients with a mutation in the PHKA2 gene. This finding may support for genetics diagnosis of unknown cause of hepatomegaly.