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Background: The main genetic cause of iron overload is haemochromatosis (HC). In recent years, the study of non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6) has become relevant thanks to next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) techniques. Our objectives were to estimate the prevalence of both HFE (C282Y/HY63D variants) and non-HFE variants attending a tertiary hospital in Aragón, to predict the effect of the variants on the protein, and to establish a genotype-phenotype correlation evaluating with the clinical context., Methods: Retrospective descriptive study from 2006 to 2020 of patients attended at genetic consultation in a reference hospital for HC in Aragon. We calculated prevalence of HFE and non-HFE variants. We analysed non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6), used bioinformatics tools, consulted different databases and measured clinical parameters (laboratory and imaging)., Results: The prevalence of C282Y homozygous was 5.95% respect the total of cases and 0.025% respect our population. The prevalence of non-HFE HC variants was 1.94% respect the total of cases and 0.008% respect our population. We found 27 variants in non-HFE genes and 4 in HFE gene, of which 6 were classified as variant of uncertain clinical significance (VUS), or likely pathogenic or pathogenic according to the ACMG classification criteria., Conclusion: Our prevalence results are as expected, and similar to those obtained by other studies. Although some of the genetic findings explain the clinical symptoms of some of our patients, we remain have a high number of patients without a clear molecular diagnosis., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Consensus guidelines for genotype-guided fluoropyrimidine dosing based on variation in the dihydropyrimidine dehydrogenase (DPYD) gene before treatment have been firmly established. The prior pharmacogenetic report avoids the serious toxicity that inevitably occurred in a non-negligible percentage of the treated patients. The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disorder characterized by the proliferation and infiltration of macrophages and hyperactivated T lymphocytes that escape from the physiological control pathways and favour the existence of an environment of excessive inflammation and tissue destruction. HLH has been classified into two types: a primary or familial autosomal recessive form, caused by mutations in genes encoding proteins involved in the granule-dependent cytotoxic pathway (familial hemophagocytic lymphohistiocytosis [FHL] types 1-5); and other secondary or acquired form, generally associated with infections, malignancy, autoimmune diseases, metabolic disorders or primary immunodeficiencies. Since the first familial hemophagocytic lymphohistiocytosis-2 (FHL2) causative mutation in the PRF1 gene was described in 1999, more than 200 mutations have been identified to date. Here, we report the first case of very late-onset FHL2 in a Spanish 72-year-old female with splenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia and marrow hemophagocytosis harbouring in heterozygosity two PRF1 variants proposed as causative in this study. The heterozygous mutation c.445G>A (p.Gly149Ser) identified in the exon 2 results in a missense mutation previously described as a probable pathogenic variant associated with the development of FHL2. Affecting the same exon, c.272C>T (p.Ala91Val) is the most prevalent variant of this gene. Although it was initially classified as benign, recent studies support its potential pathogenic role, considering it a variant of uncertain significance associated with a risk of developing FHL2. The genetic confirmation of FHL made possible an adequate counselling to the patient and direct relatives and provided important information for her control and follow-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD., Objective: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD., Methods: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined., Results: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels., Conclusions: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD., (©Ricardo González-Tarancón, Nuria Goñi-Ros, Elvira Salvador-Rupérez, Ángela Hernández-Martín, Silvia Izquierdo-Álvarez, José Puzo-Foncillas, Yolanda Gilaberte-Calzada. Originally published in JMIR Dermatology (http://derma.jmir.org), 27.06.2023.)

Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy is a primary microgliopathy characterized by a complex phenotype, which can be easily misdiagnosed with other leukoencephalopathy and neurodegenerative diseases such as frontotemporal dementia. It is estimated to be the most common adult-onset leukodystrophy. Here, we report the case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions, including apathy, inhibition, tendency to mutism, and deficits in complex planning skills. Neurological examination revealed pyramidalism in the lower limbs. Brain imaging showed symmetrical confluent frontal leukoencephalopathy, bilateral frontal calcifications, and thinning of the corpus callosum. The diagnosis was confirmed by the identification of a heterozygous pathogenic variant in the colony-stimulating factor 1 receptor. As far as we know, this is the first documented case in Spain. In this paper, we aim to expand on clinical features and underline the importance of brain imaging for the diagnosis of an entity that we consider to be underdiagnosed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: The presence of microdeletions in the Y-chromosome azoospermia factor (AZF) region (YCMs) is considered the most frequent genetic cause of male infertility along with Klinefelter syndrome. The objective of this study was to investigate the frequencies and type of YCMs in infertile men in Aragon and to analyze the relationship between sex hormones, sperm count and microdeletions in them., Patients and Methods: Retrospective descriptive study of 644 men who during 2006-2019 were screened for YCMs using YChromStrip (Operón, Spain) by PCR+reverse hybridization, spermiogram, karyotype and quantification of sex hormones., Results: The frequency of YCMs was 3.88% (25/644), not being detected in any patient with mild or normospermic oligozoospermia, that is, in sperm counts higher than 5×10 6 /mL. The group of azoospermic patients was the one that presented a higher frequency of YCMs (14.58%, 14/96). Deletions in the AZFc region were the most frequent (68%). 20% (5/25) of patients with YCMs also presented some type of karyotype abnormality that included aneuploidies, deletions, duplications and/or translocations. Sperm count was significantly lower and FSH and LH concentrations significantly higher in the group of patients with YCMs., Conclusions: YCMs screening is a key test in the diagnostic approach to male infertility. Obtaining an adequate result allows choosing suitable assisted reproduction techniques, preventing unnecessary treatments and the transmission of genetic defects to offspring., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Allan-Herndon-Dudley syndrome is a rare X-linked genetic disorder, caused by a deficiency of the monocarboxylate transporter 8 (MCT8), a specific transporter of thyroid hormones, with functions mainly at the brain level. The syndrome produces an early onset of severe neurological disorder, in which hypotonia predominates., Objective: To present a rare case with an unexpected diagnosis, highlighting the usefulness of requesting a complete thyroid profile in every hypotonic male infant without a specific cause., Clinical Case: A 10-month-old male infant with severe axial and peripheral hypotonia, global weakness with little spontaneous mobility, without head support or stable sitting. Complete metabolic and peripheral neurophysiological studies were performed. Genetic studies for spinal muscular atrophy, Prader Willi syndrome, and myotonic dystrophy were also performed. The trio exome analysis detected a probably pathogenic variant c.359C>T;p.(Ser120Phe), hemizygous in exon 1 of the SLC16A2 gene, inherited from the mother. Thyroid abnormalities as increased free triiodothyronine (T3) and thyroid-stimulating hormone (TSH), and delayed myelination were ob served., Conclusions: MCT8 deficiency should be considered in the case of the male infant with unex plained hypotonia and weakness without a determined cause. The diagnosis is guided by a thyroid profile including free T3 hormone, because it presents a characteristic thyroid profile with decreased free thyroxine (T4), increased free T3, and normal or slightly elevated TSH levels. In this case, the implementation of the trio exome analysis allows establishing an early certain diagnosis.

ISO 15189:2012 establishes the requirements for clinical sample management, ensuring quality of process and laboratory information management. The accreditation authority, ENAC in Spain, established the requirements for the authorized use of the label in reports issued by accredited laboratories. These recommendations are applicable to the postanalytical processes and the professionals involved. The Standard requires laboratories to define and document the duration and conditions of sample retention. Laboratories are also required to design an internal quality control scheme to verify whether postanalytical activities attain the expected standards. Information management requirements are also established and laboratories are required to design a contingency plan to ensure the communication of laboratory results. Instructions are finally provided about the correct use of the accreditation label in laboratory reports. A range of nations and scientific societies support that clinical laboratories should be required to obtain accreditation. With ISO 15189 being the most specific standard for demonstrating technical performance, a clear understanding of its requirements is essential for proper implementation., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Mᵃ Libòria López Yeste et al., published by De Gruyter, Berlin/Boston.)

Introduction: The incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation)., Methods: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000)., Results: The incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=-0.547; 95%CI: -0.610 to -0.375; P<.001). CTG 5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent., Conclusions: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To assess the effectiveness of incorporating hygienic-dietary recommendations in laboratory reports in reducing the incidence of renal colic (RC). A study was performed to compare the incidence of RC in two groups of patients who had suffered at least a crystalluria event associated with the risk of urolithiasis. Recommendations were only incorporated in the laboratory reports of one group., Methods: A retrospective observational study. The study sample was composed of patients who had at least an episode of crystalluria associated with a higher risk of urolithiasis. The laboratory reports of patients in Group A (n=1,115), treated in 2017, did not include any hygienic-dietary recommendations, whereas patients in Group B (n=1,692), treated in 2018, received hygienic-dietary recommendations through their laboratory reports. χ 2 and Mann-Whitney U test were used to assess differences based on sex, age, and type of urinary crystals., Results: The incidence of RC was 2.02 times higher in group A (2.24%) than in group B (1.12%). No significant differences were observed in the incidence of RC based on the type of urinary crystal. The incidence of RC was substantially higher in patients who suffered at least an event of crystalluria associated with a higher risk for urolithiasis as compared to the general population during the same period (0.46%, consistently with the incidence rates reported in the literature)., Conclusions: The incorporation of messages alerting on the risk of urolithiasis and the inclusion of hygienic-dietary recommendations in laboratory reports may be useful for reducing the incidence of RC., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Paula Sienes Bailo et al., published by De Gruyter, Berlin/Boston.)

The objective of this paper is to share some considerations about the management of postanalytical processes in relation to the review, reporting and release of test results in accordance with UNE-EN ISO 15189:2013 Standard requirements. The scope of this paper includes postanalytical activities and the personnel involved (laboratory management and staff). We describe the criteria and information required to review and validate analytical results and ensure that clear reports are sent to requesters. These criteria also guarantee that results are transcribed in a reliable way and that all necessary information is provided for the correct interpretation of results. Likewise, the requirements for the correct release of laboratory results are described, with special emphasis on the release of alarming or critical results. In some European countries, clinical laboratories are required to hold partial or full ISO 15189 accreditation, which is a global trend. Therefore, understanding ISO 15189 requirements is imperative for a progressive and more effective implementation of the Standard., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Mᵃ Liboria López Yeste et al., published by De Gruyter, Berlin/Boston.)

Background: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases., Methods: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007-2019 in Aragon (Spain)., Results: 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16., Conclusions: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

There are four classes of CGG repeat alleles in the FMR1 gene: normal alleles have up to 44 repeats; patients with Fragile X Syndrome have more than 200 repeats; those between 55 and 200 CGGs are considered FMR1 premutation alleles, because they are associated with maternal expansions of the number of CGGs in the next generation and finally, alleles between 45 and 54 CGGs are called intermediate or gray zone alleles. In these last categories, the stability depends on the presence of AGG interruptions, which usually occurs between 9 and 10 CGGs. In this context, we have studied retrospectively 66 women with CGG repeats between 45 and 65, and their offspring. In total 87 transmissions were analyzed with triplet repeat primed PCR using AmplideX® FMR1 PCR (Asuragen, Austin, TX, USA) and we found that alleles with CGG repeats between 45 and 58 do not expand in the next generation except two cases with 56 repeats and 0 AGG interruptions. Furthermore, we have found four females with alleles with more than 59 CGG repeats and 2 AGG interruptions that do not expand either. Alleles from 56 CGG repeats without AGGs expand in all cases. In light of these results and those of the literature, we consider that the risk of unstable transmissions should be based on the presence or absence of AGG interruptions and not on the classical cutoffs which define each category of FMR1 alleles. The application of these results in the genetic and reproductive counseling is essential and AGG interruptions should always be studied., (Copyright © 2020 Villate, Ibarluzea, Maortua, de la Hoz, Rodriguez-Revenga, Izquierdo-Álvarez and Tejada.)

Background: The main exposure route to methylmercury (MeHg) is from eating fish and shellfish containing this compound. Since 2004, women of childbearing age in Spain have been urged not to eat some species (eg, tuna, shark, and swordfish), instead choosing low-MeHg seafood as part of a healthy diet., Objective: To describe maternal total blood mercury (THg) and serum selenium (Se) in a cohort of pregnant women living in Spain as it relates to fish intake during the three trimesters and to assess whether or not Spanish women of childbearing age follow the recommendations listed in fish advisories and choose fish species with lower mercury levels., Methods: We studied 141 female volunteers of childbearing age (16-45 years), interviewing all participants about their overall eating habits and seafood intake. Hg and Se levels were tested using cold-vapor atomic absorption spectrometry (CVAAS) and electrothermal atomic absorption spectrometry (ETAAS), respectively., Results: Average THg levels in pregnant women were 2.89 μg/L (standard deviation [SD], 2.75 μg/L, geometric mean [GM], 2.19 μg/L), and THg GM was positively associated with fish intake. Mean Se levels in pregnant women were 73.06 μg/L (SD, 13.38 μg/L), and Se levels were found to increase with tuna intake. In 16 (12%) pregnant women, THg was higher than the level recommended by the U.S. Environmental Protection Agency (EPA) (6.4 μg/L). A positive association was also found between THg and serum Se., Conclusion: Women of childbearing age in Spain had higher THg levels than women in other Western studies. Our study observed that 12% of women had THg levels above the safety limit set by the EPA (6.4 μg/L), and 31% had levels above the relevant benchmark level of 3.5 μg/L suggested by various researchers., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Rasopathies are a group of genetic malformative syndromes including neurofibromatosis 1, Noonan, LEOPARD, Costello, cardio-facio-cutaneous, Legius, and capillary malformation-arteriovenous malformation syndromes., Case Presentation: We present a female newborn that consulted at the emergency department with refusal to eat and sleepiness. A shortened femur, thickened nucal fold and suspect for agenesis of the corpus callosum were observed in prenatal ultrasound. Her phenotype included hypertelorism, antimongoloid obliquity of the palpebral fissure, prominent forehead, long filtrum, thickened nucal fold, separated nipples, widespread thickened skinfolds and café-au-lait spots. She had a systolic murmur due to pulmonary valve stenosis. The NF1 gene testing found the pathogenic variant p.E2586X (c.7756G > T) in exon 53, not described in any international database or scientific publications yet. Also, a mutation in the Kras gene was detected (p.Val14lle), which is associated with mild Noonan phenotype. Both variations were de novo., Conclusions: Not all genes and mutations have already been discovered, so it's important to document new findings, like our patient's, to enrich and update the international database and broaden all possible knowledge about rasopathies. This is the first case to be described presenting simultaneously two mutations in Kras and NF1 genes, whose possible synergic effect regarding its pathogenicity is unknown, but could be interesting towards therapeutic alternatives.

Introduction: Hair samples are used as a tool to evaluate environmental exposure to contaminants and metabolic status in the individual. However, the use of human hair is controversial, mainly because of the lack of well-defined reference levels. In the case of Spain, very few biomonitoring studies have investigated these issues in infants, children or adolescents., Objective: To establish reference levels for trace elements in children and teenagers in Madrid, Spain., Material and Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Al, As, Ag, Ba, Bi, Cd, Cr, Co, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sr, Tl and Zn levels in hair samples from 648 healthy children and adolescents (253 boys and 395 girls) between April 2008 and December 2009., Results: Median levels were as follows: Al 18.5μg/g, As 0.07μg/g, Ag 196ng/g, Ba 0.5μg/g, Bi 0.01μg/g, Cd 18.3ng/g, Cr 0.4μg/g, Co 14.5ng/g, Cu 25.7μg/g, Fe 15.5μg/g, Mn 328ng/g, Mo 0.04μg/g, Ni 0.5μg/g, Pb 0.70μg/g, Se 0.5μg/g, Sr 1.29μg/g, Tl 0.28ng/g and Zn 121μg/g., Discussion and Conclusion: The values of trace elements here described could be considered as possible reference ranges for hair samples from children and adolescents aged 0-18 years living in the Madrid region (central Spain). These values could also be selected as a preliminary screening tool to assess exposure sources and to generate information needed to develop prevention strategies and likewise could be a complement to other diagnostic procedures., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Blood hemoglobin (Hb) concentration within the reference interval does not exclude iron deficiency (ID): individuals with normal stores lose iron during a long period before their Hb falls below of the level that is defined as anemia. The process entails a decrease of storage iron, shown by serum ferritin below reference range, followed by iron depletion, eventually leading to iron restricted erythropoiesis; consequence of an imbalance between erythropoietic iron requirements and too low supply is a reduction of Hb synthesis in reticulocytes., Objective: We study the potential utility of mean reticulocyte hemoglobin content (MCHr), reported by CELL-DYN Sapphire (Abbott Diagnostics) analyzer, in the detection of ID in non-anemic adults., Methods: 207 patients with Hb within the reference range were enrolled. ID was defined as Hb>120g/L (women), >130g/L (men) and serum ferritin <30μg/L. Student's t-test was applied to detect deviations between groups, statistical significance P<0.05. The performance of MCHr in detecting ID was evaluated applying Receiver Operating Characteristic (ROC) curve analysis. Kappa test was applied to verify concordance between ferritin and MCHr., Results: 68 patients (33%) suffered ID, median MCHr in this group was 26.9 pg, statistically different from the normal group, MCHr 30.9pg (P<0.0001). ROC ANALYSIS (GOLD STANDARD FERRITIN <30μG/L): Area under curve AUC 0.851 (95% CI 0.770-0.912) at cut off 30.0 pg, with sensitivity 84.1% and specificity 71.1%. Kappa 0.667 (95% CI 0.527-0.858)., Conclusion: Due to their short lifespan reticulocytes and derived parameters reflect current erythropoiesis status, before Hb and erythrocyte indices drop. MCHr had the best AUC and diagnostic value compared to erythrocyte indices. MCHr is a reliable test for the investigation of ID and could improve the detection of iron deficient adults., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Very few studies exist on urinary arsenic exposure in Spain., Objective: To evaluate total and speciated urinary arsenic (As) levels in a Spanish population sample., Methods: Demographic, lifestyle and dietary data was collected for 124 volunteers (aged 20-76years; 88 women and 36 men), who were tested for total arsenic and five arsenic species using high-performance liquid chromatography-inductively coupled plasma mass spectrometry., Results: Arsenobetaine (AB) and dimethylarsinic acid (DMA) were detected in 96.8% of the study participants (limit of detection (LOD) 1.0μg/L for AB and 1.9μg/L for DMA). Monomethylarsonic acid (MMA) and arsenous acid (As(III)) were detected in 5.6% (LOD 1.8μg/L) and 1.6% (LOD 1.4μg/L) of the participants, respectively; arsenic acid (As(V)) was not detected (LOD 1.4μg/L). AB and DMA (geometric mean (GM) 29.1μg/L and 7.5μg/L, respectively) were the main contributors to total urinary arsenic levels. Urinary DMA was positively associated with AB., Conclusion: Total arsenic levels observed in the Spanish population sample were higher than those reported by other European studies. The most recurrent urinary arsenic species was AB, followed by DMA, probably attributable to the high Spanish consumption of seafood. We recommend using inorganic As+MMA as the two main urinary biomarkers for inorganic As exposure. Our results provide reference data for analysing arsenic speciation results and assessing human exposure., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The simultaneous presence of a heterozygous β-thalassemia with α-gene triplication may cause anything from a thalassemia trait to thalassemia intermedia of mild to moderate severity., Case Presentation: An 8-month-old ethnic Gypsy male infant with failure to thrive from birth, mild jaundice and splenomegaly. Clinical signs were compatible with severe microcytic anemia requiring bi-monthly blood transfusions. The β-thalassemia gene analysis found homozygous mutation IVS-I-110 (G>A) (c.93-21G>A) in intron 1 of the hemoglobin beta globin gene and a non-pathogenic sequence variant (single nucleotide polimorfism (SNP) Rs1609812). In addition, the patient had α gene triplication (ααα(anti 3.7)/αα) caused by double heterozygosity for a 3.7 kb fragment that contained only the hemoglobin alpha globin gene-2 gene. This finding led to screening and follow up in first-degree relatives, twin brothers and a sister and parents to provide them with appropriate genetic counseling. Nowadays, new horizons could open a new therapeutic management until definitive cure of these diseases through gene therapy or mutation-specific genome editing., Conclusions: Genetic testing can provide an early diagnosis and facilitates the search for a suitable donor for transplantation.

Introduction: The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS., Clinical Observation and Methods: CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation., Results: Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS., Discussion: Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI)., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)