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Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next‐generation sequencing‐based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73‐gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non‐LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann‐Pick disease B, Gaucher disease) and three with non‐LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost‐effective screening of LDs and disorders sharing with them early clinical signs.

At the present time the so-called parallel or next generation sequencing (NGS) technique is rapidly expanding and developing; this process establishes a jump by several orders of magnitude in the length of the fragments sequenced and the speed with which this sequencing is carried out. NGS allows a whole human genome to be sequenced in the same amount of time and with the same economic cost required to sequence two or three large genes using the Sanger technique. Use of NGS allows us to go from examining specific genes selected by studying the phenotype to exploring whole genomes of groups of humans or other species. This is making it possible to know not only what an individual genome is like but also how the human genome changes from one person to another, how genomes differ from one group of humans to another, and even how the genome differs in a tumour with respect to the healthy genome of the host.

A number of genetic and neuroimagen proofs support the idea that attention-deficit/hyperactivity disorder (ADHD) present a neurobiological alteration. Vesicular monoamine transporters (VMATs) are important proteins that regulate the intraneuronal monoamine concentration and disposition as this protein sequesters cytoplasmic dopamine within synaptic vesicles thus contributing to subsequent excitotoxic release.Two pharmacologically distinct VMAT isoforms VMAT1 and VMAT2 have been cloned and described. The VMAT2, in the CNS, is responsible for the translocation of dopamine from the cytoplasm into synaptic vesicles. In addition, it has been described a neuroprotector role for these transporters. The platelet vesicular monoamine transporter VMAT2 is used as a peripheral model of neuronal VMAT2. Its quantification has been used to perform studies of ADHD and other neuropsychiatry diseases related with the monoamines metabolism.Since dopamine and other monoamines (epinephrine and serotonine) play a role in ADHD, and methylphenidate, an usual treatment for this type of patients, modifies the VMAT2 activity, we may argue that VMAT2 is involved in ADHD pathogeny.

Objective: Moderate hyperhomocyst(e)inemia is an independent risk factor for stroke, but it is unclear whether it also would be a risk factor for secondary vascular events after stroke. Methods: Longitudinal study of 137 consecutive ischemic stroke patients (age 45–91 years) who were prospectively studied with a standard clinical protocol. Vascular events (stroke recurrence, ischemic heart disease, deep venous thrombosis or peripheral arterial disease) were identified during 2 years of follow-up. Serum homocyst(e)ine was determined 3 months after the stroke. The cumulative proportion of patients with homocyst(e)ine above or below the 75th percentile who survived free of vascular events was determined by Kaplan-Meier analysis. Cox models were used to estimate the relative risk of vascular events after controlling for other confounding factors. Results: Serum homocyst(e)ine was significantly higher in patients with vascular events (26.2 versus 19.4 µmol/l; p = 0.016). The cumulative proportion of patients with vascular events was 46.5% in the group with homocyst(e)ine over the 75th percentile (>30 µmol/l) and 20.2% in the other group (log-rank test 7.5; p = 0.0062). After adjustment for age, sex, high blood pressure, diabetes, heart disease, previous cerebrovascular disease, smoking and serum cholesterol, the relative risk of vascular event for patients above compared with those below the 75th percentile of serum homocyst(e)ine was 2.8 (CI 95% 1.3–6; p = 0.01). Conclusion: Hyperhomocyst(e)inemia is a significant risk factor for vascular events after ischemic stroke. This finding is independent of other risk factors such as hypertension, and may have therapeutic relevance in the secondary prevention of vascular diseases in stroke patients.