Metabolic disorders are due to a deficiency of enzymes, which can severely impact health or cause serious complications without treatment. This study aimed to identify the molecular causes of an infant death who had been hospitalized with complicated health problems and metabolism syndrome. Whole-exome sequencing (WES) was used to screen pathogenic variants in the patient’s genome, followed by examination of variants segregation in her parents. The WES analysis identified two homozygous variants, c.[614C>G; 649A>G] in the HMGCL gene of the patient. These two variants co-locate within the exon 7 of the HMGCL gene, resulting in 2 amino acid substitutions, p.[T205S; M217V], in the conservative region of enzyme protein. Sanger sequencing showed that the patient’s unaffected mother and father carried one mutant allele of the HMGCL gene containing two c.[614C>G; 649A>G] variants. The HMGCL gene encodes the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme, which is critical in the ketogenic pathway. The deficiency of this enzyme was reported to be a life-threatening illness in the neonatal period, and two variants detected in this study were also found in a Japanese patient with sudden, unexpected death in infancy. The frequency of these two variants in the Vietnamese in-hour database and their further functional analysis were also reported in this study. The results of this study have explored the molecular etiology that causes the severe, deadly condition of the patient and provide an understanding of the risk of disease in her family.

Type 2 diabetes mellitus (DM) and hypertension (HT) are common major cardiovascular disease (CVD) risk factors. They share common pathophysiological mechanisms and are commonly co-existent. Prevalence of HT is increased among diabetic patients but also DM is more common in hypertensive patients. CVD risk increases multiplicatively in coexistence of HT and DM. Lowering blood pressure (BP) has been shown to be associated with improved morbidity related to both macro- and micro-vascular complications. Although there is debate about target BP levels, in many randomized controlled trials and guidelines a goal of < 130/80 mmHg is advocated in patients with DM, if well tolerated. However, an individualized approach should be cared for depending on risk factors, co-morbidities, and frailty of patients. Lifestyle modifications including weight loss, regular exercise, avoiding smoking and excessive alcohol consumption, and a healthy diet including limitation of salt and fat and total energy intake, are important both as a part of preventive therapy and treatment modality for both DM and HT. Among antihypertensive drugs angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are warranted due to their potential advantages for slowing albuminuria and progression to kidney failure which is more common in DM. Usually, their combination with calcium-channel blockers (CCBs) or thiazide/thiazide-like diuretics, in a step-wise manner, is recommended. Resistant HT is more common in DM and requires the addition of mineralocorticoid receptor antagonists (MRAs). New antidiabetic drugs like glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to lower BP. Apart from their antihypertensive effects they also improve CVD and renal outcomes. There’re ongoing new trials for new agents. Development of more potent and longer-term effective BP lowering drugs, single pill multiple drug combinations of antiHT agents and combination of antiHT agents with glucose-lowering and antilipidemic agents will probably improve compliance to treatment and achievement of goals in diabetic patients.