Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare metabolic disorder that impairs the body’s ability to produce ketone bodies and regulate energy metabolism. Diagnosing HMGCS2D is challenging because patients typically remain asymptomatic unless they experience fasting or illness. Due to the absence of reliable biochemical markers, genetic testing has become the definitive method for diagnosing HMGCS2D. This study included 19 patients from 14 unrelated families diagnosed with HMGCS2D in our department between October 2018 and October 2024. The clinical presentations, biochemical findings, molecular characteristics, and management strategies were systematically summarized and analyzed. Of the 19 cases studied, 16 were symptomatic, and 3 were asymptomatic. The onset of the first acute episode occurred between 10 days and 28 months of age. Triggers for the initial crisis in the symptomatic cases included poor feeding (93.8%), vomiting (56.3%), diarrhea (25.0%), and fever (18.8%). Clinical manifestations during the first episode were lethargy/coma (81.3%), rapid breathing (68.8%), hepatomegaly (56.3%), shock (37.5%), and seizures (18.8%). The biochemical abnormalities observed included elevated plasma transaminases (100%), metabolic acidosis (75%), hypoglycemia (56.3%), and elevated plasma ammonia levels (31.3%). Additionally, low free carnitine levels were found in seven cases, elevated C2 levels were found in one case, dicarboxylic aciduria was found in two cases, and ketonuria was found in two cases. Abnormal brain MRI findings were detected in three patients. Genetic analysis revealed seven HMGCS2 gene variants across the 19 cases. Notably, a novel variant, c.407A>T (p.D136V), was identified and has not been reported in any existing databases. Two common variants, c.559+1G>A and c.1090T>A (p.F364I), were present in 11 out of 19 cases (57.9%) and 10 out of 19 cases (55.5%), respectively. The implementation of a high glucose infusion and proactive management strategies—such as preventing prolonged fasting and providing enteral carbohydrate/glucose infusion during illness—effectively reduced the rate of acute relapses following accurate diagnosis. Currently, all 19 patients are alive, with ages ranging from 5 months to 14 years, and exhibit normal physical development. To the best of our knowledge, this study represents the first reported cases of HMGCS2D in Vietnamese patients. Our findings contribute to a broader understanding of the clinical phenotype and expand the known spectrum of HMGCS2 gene variants, enhancing current knowledge of this rare metabolic disorder.

Background: Genetic testing can potentially transform the management of critically ill adults in intensive care units. However, the implementation of genetic testing in resource-limited settings across Asia and Africa faces distinct challenges. Objective: This review summarizes the challenges and opportunities related to genetic testing in adult intensive care units within these regions. Methods: We synthesized findings based exclusively on the published literature, focusing on issues specific to Asian and African populations. Results: The high genetic diversity in these populations and their limited representation in global genomic databases create difficulties in interpreting genetic variants and applying pharmacogenomic data. Despite these challenges, there are clear opportunities to improve the diagnosis of unexplained critical illnesses, optimize drug therapies, and enhance risk prediction in critical care. Major obstacles include limited infrastructure, high costs, and a lack of local genomic data. Conclusion: Collaborative strategies are essential in advancing genetic testing in these settings. Key priorities include building sustainable local capacity, generating population-specific genomic data, adopting cost-effective technologies, engaging communities to develop ethical guidelines, and establishing supportive government policies. A strategic and context-specific approach is needed to integrate genetic testing into critical care and improve outcomes in Asia and Africa.

Purpose: This study aims to estimate the incidence and examine the clinical and laboratory characteristics of newly diagnosed type 1 diabetes (T1D) in Vietnamese children at a tertiary referral pediatric hospital.Methods: A retrospective cross-sectional analysis was conducted on 64 children newly diagnosed with T1D at Vietnam National Children's Hospital in 2023. Data on the children were analyzed, including demographics, family history, symptoms, anthropometric measurements, hemoglobin A1c levels, and pancreatic islet autoantibodies.Results: The average age at diagnosis was 9.1±3.7 years, with a male predominance (53.1%). The incidence rate of T1D in these northern Vietnamese children was 0.77 per 100,000 children. Diabetic ketoacidosis (DKA) was present in 57.8% of children at diagnosis, and 75% tested positive for autoantibodies. The Red River Delta reported the highest proportion of children with T1D (43.5%), but the incidence rate was highest in Hanoi, the capital city (0.91 per 100,000 children).Conclusion: This study underscores the considerable diagnostic delays in T1D in a tertiary pediatric center in Vietnam, with a high prevalence of DKA. The results highlight the need for an enhanced network of satellite hospitals to enable early diagnosis and treatment for patients.

Skin, as the body’s primary environmental interface, is continuously exposed to various environmental stressors that significantly impact its genomic integrity and accelerate aging processes. This mini review summarizes current knowledge of the molecular mechanisms behind environmentally induced skin aging, focusing especially on how ultraviolet radiation affects skin genomics. Recent research (2010–2025) has revealed breakthrough findings in the “skin exposome” concept, demonstrating that UV radiation creates characteristic signature mutations with distinct T>C transitions alongside the canonical C>T transitions and activates complex molecular pathways leading to photoaging. Beyond UV radiation, air pollution and lifestyle factors contribute to skin aging through overlapping yet distinct molecular mechanisms, with emerging evidence highlighting significant synergistic effects. Recent clinical studies demonstrate that epigenetic modifications, particularly DNA methylation alterations, mediate long-term environmental impacts on skin and represent potentially reversible targets for intervention. This review critically examines genome-driven protective strategies, including antioxidant interventions targeting the Nrf2/ARE pathway and personalized approaches based on genetic susceptibility while analyzing the practical barriers to their implementation.