Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL

The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient's fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient's clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this disease

Clinical characteristics, treatment, and blood pressure control in patients with hypertension seen by primary care physicians in Spain: the IBERICAN study

Objectives: To determine the clinical profile, according to the history of hypertension, the risk of developing hypertension, current antihypertensive treatment and BP control rates in patients with hypertension from the IBERICAN cohort. Methods: IBERICAN is an ongoing prospective cohort study, whose primary objective is to determine the frequency, incidence, and distribution of CVRF in the adult Spanish population seen in primary care settings. This analysis shows the baseline clinical characteristics of patients with hypertension. Adequate BP control was defined as BP <140/90 mmHg according to 2013 ESH/ESC guidelines. Results: A total of 8,066 patients were consecutively included, of whom 3,860 (48.0%) had hypertension. These patients were older (65.8 ± 10.9 vs. 51.6 ± 14.7 years; p < 0.001), had more cardiovascular risk factors, target organ damage and cardiovascular disease (CVD) in comparison with those without hypertension. The risk of hypertension increased with the presence of associated CV risk factors and comorbidities, particularly diabetes, obesity and the metabolic syndrome, and decreased with the intensity of physical activity. Regarding antihypertensive treatments, 6.1% of patients did not take any medication, 38.8% were taking one antihypertensive drug, 35.5% two drugs, and 19.6% three or more antihypertensive drugs. Overall, 58.3% achieved BP goals <140/90 mmHg. A greater probability of BP control was observed with increasing age of patients and the greater number of antihypertensive drugs. Blood pressure control was lower in hypertensive patients with diabetes, obesity, the metabolic syndrome, increased urinary albumin excretion, higher pulse pressure, and lack of antihypertensive treatment. Conclusions: About half of patients attended in primary care settings have hypertension in Spain. Patients with hypertension have a worse CV clinical profile than non-hypertensive patients, with greater association of CVRF and CVD. Around four out of ten patients do not achieve the recommended BP goals, and higher use of combination therapies is associated with a better BP control

Prevalence of Hyperuricemia and Its Association with Cardiovascular Risk Factors and Subclinical Target Organ Damage

The role of uric acid levels in the cardiovascular continuum is not clear. Our objective is to analyze the prevalence of hyperuricemia (HU) and its association with cardiovascular risk factors (CVRF), subclinical target organ damage (sTOD), and cardiovascular diseases (CVD). We evaluated the prevalence of HU in 6.927 patients included in the baseline visit of the IBERICAN study. HU was defined as uric acid levels above 6 mg/dL in women, and 7 mg/dL in men. Using adjusted logistic regression models, the odds ratios were estimated according to CVRF, sTOD, and CVD. The prevalence of HU was 16.3%. The risk of HU was higher in patients with pathological glomerular filtration rate (aOR: 2.92), heart failure (HF) (aOR: 1.91), abdominal obesity (aOR: 1.80), hypertension (HTN) (aOR: 1.65), use of thiazides (aOR: 1.54), left ventricular hypertrophy (LVH) (aOR: 1.36), atrial fibrillation (AFIB) (aOR: 1.29), and albuminuria (aOR: 1.27). On the other hand, being female (aOR: 0.82) showed a reduced risk. The prevalence of HU was higher in men, in patients presenting CVRF such as HTN and abdominal obesity, and with co-existence of LVH, atrial fibrillation (AFIB), HF, and any form of kidney injury. These associations raise the possibility that HU forms part of the early stages of the cardiovascular continuum. This may influence its management in Primary Healthcare because the presence of HU could mean an increased CV risk in the patients

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx(R). Our aim was to establish the effectiveness of LipoDDx(R). Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx(R). The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx(R) provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx(R) the success rate was 17 +/- 20%, while with LipoDDx(R) the success rate was 79 +/- 20% (p < 0.01). CONCLUSIONS: LipoDDx(R) is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value

Should we suspect primary aldosteronism in patients with hypokalaemic rhabdomyolysis? A systematic review

Severe hypokalaemia causing rhabdomyolysis (RML) in primary aldosteronism (PA) is a rare entity, and only a few cases have been reported over the last four decades. This systematic review and case report aims to gather all published data regarding a hypokalaemic RML as presentation of PA in order to contribute to the early diagnosis of this extremely rare presentation. With the use of PubMed Central, EMBASE, and Google Scholar, a thorough internet-based search of the literature was conducted to identify articles and cases with RML secondary to hypokalaemia due to PA between June 1976 and July 2023. The case study concerns a 68-year-old male patient with hypokalaemic RML at presentation of PA. In the systematic review of the literature, 37 cases of RML secondary to hypokalaemia due to PA have been reported to date. In summary, the median age was 47.5 years, the male/female ratio was 17/21, all patients presented symptoms (weakness and/or myalgia), all the patients were hypertensive, and only four patients had complications with acute kidney injury (AKI). Although PA rarely presents with RML, it should be suspected when marked hypokalaemia and hypertension are also present. Early detection and management are essential to reduce the frequency of manifestations such as AKI

TERAPIAS EMERGENTES. ¿NUEVAS SOLUCIONES PARA VIEJOS PROBLEMAS?

A pesar de los ímprobos esfuerzos encaminados a su prevención, la enfermedad cardiovascular continúa siendo hoy la principal causa de morbimortalidad a nivel mundial, con casi 18 millones de vidas perdidas anualmente1. Por este motivo, urge encontrar nuevas estrategias que limiten su progresión y la de sus principales factores de riesgo (hipertensión arterial, obesidad, diabetes, dislipemias, …)