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INTRODUCTION: Neonates in a NICU experience pain. Based on the cardiovascular and nociceptive systems link, a Newborn Infant Parasympathetic Evaluation (NIPE) monitor was designed to assess pain. The use of α2-agonists as analgesic-sedative drugs has increased in neonates. Given their effect on the autonomic system, we hypothesized that their use may alter NIPE's measurement capacity. METHODS: Data were prospectively collected. The included patients were evaluated using combined pain assessment systems. RESULTS: Sixteen newborns requiring sedoanalgesia underwent a total of 84 pain assessments. A good correlation was found between the NIPE-index and the COMFORT-neo and the crSO2 (cerebral regional oxygen saturation). No correlation was found in premature infants. By sedation group, the correlation remained in those receiving α2-agonist. CONCLUSION: NIPE is a reliable tool for pain assessment. Further studies in premature infants are needed. The use of α2-agonist does not alter the measuring capacity of NIPE. The correlation between NIPE-index and crSO2 was also demonstrated.
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CONTEXT.: Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations. OBJECTIVE.: To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries. DESIGN.: A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published in the literature to date. RESULTS.: Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries. CONCLUSIONS.: ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.
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Supplementation is crucial for improving performance and health in phenylketonuria (PKU) patients, who face dietary challenges. Proteins are vital for athletes, supporting muscle growth, minimizing catabolism, and aiding muscle repair and glycogen replenishment post-exercise. However, PKU individuals must limit phenylalanine (Phe) intake, requiring supplementation with Phe-free amino acids or glycomacropeptides. Tailored to meet nutritional needs, these substitutes lack Phe but fulfill protein requirements. Due to limited supplement availability, athletes with PKU may need higher protein intake. Various factors affect tolerated Phe levels, including supplement quantity and age. Adhering to supplement regimens optimizes performance and addresses PKU challenges. Strategically-timed protein substitutes can safely enhance muscle synthesis and sports performance. Individualized intake is essential for optimal outcomes, recognizing proteins' multifaceted role. Here, we explore protein substitute supplementation in PKU patients within the context of physical activity, considering limited evidence.
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Fenilalanina , Fenilcetonurias , Humanos , Fenilalanina/metabolismo , Dieta , Suplementos Dietéticos , Ejercicio Físico , Fenilcetonurias/metabolismoRESUMEN
Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.
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Infección Hospitalaria , Neonatología , Recién Nacido , Humanos , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Morbilidad , Incidencia , Atención a la SaludRESUMEN
Recent years have seen growing interest in hair sample analysis to detect organic pollutants (OPs). This biological matrix can be analysed non-invasively for biomonitoring of OPs over a wide exposure window. Obtaining hair sample amounts that meet the needs of the analytical methodology required for the determination of the POs of interest can be challenging, especially in infants. As a result, studies assessing organic pollutants in infant hair have been very scarce. We quantified levels of about 60 OPs, including persistent organic pollutants (POPs), in 110 hair samples from a patient cohort (60 mothers and 50 infants) from Santiago de Compostela (north-western Spain). For each participant we examined relationship between OP levels and corresponding epidemiological parameters using correlations, principal component analysis (PCA), hierarchical cluster analysis, and Multivariate analysis of variance (MANOVA). For many OPs we observed significant correlations with place of residence, parity, and maternal age, as well as pet ownership. Evaluation of dietary habits showed significant associations between levels some OPs and the consumption of fish, molluscs, and cereal. There were significant associations between chlorpyrifos and deltamethrin levels and infant birth characteristics such as birthweight and head circumference. Relations between OP levels in the hair of mothers and their infants were also examined, revealing common sources of exposure for dioxin-like polychlorinated biphenyls (DLPCBs), non-dioxin-like polychlorinated biphenyls (NDLPCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Levels of fluoranthene (F), pyrene (P), endrin, and some PBDEs in maternal hair were significantly correlated with those in infant hair. Our findings identified common sources of exposure to OPs of distinct chemical classes.
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Contaminantes Ambientales , Bifenilos Policlorados , Embarazo , Femenino , Animales , Humanos , Lactante , Contaminantes Ambientales/análisis , Bifenilos Policlorados/análisis , Monitoreo Biológico , Análisis de Cabello , España , Éteres Difenilos Halogenados/análisis , Monitoreo del Ambiente/métodosRESUMEN
Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.
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Lactancia Materna , Leche Humana , Lactante , Femenino , Humanos , Aminoácidos , Aminoácidos Esenciales , Estado NutricionalRESUMEN
BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.
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Mucopolisacaridosis III , Humanos , Mucopolisacaridosis III/tratamiento farmacológico , Mucopolisacaridosis III/genética , Heparitina Sulfato , Encéfalo , Hígado , BazoRESUMEN
Evaluation of postnatal exposure to organic pollutants is especially important for suckling infants during breastfeeding, a crucial perinatal growth period when organs and hormonal systems develop. We determined levels of 60 pollutants, including organochlorine pesticides (OCPs), organophosphorus pesticides (OPPs), pyrethroids (PYRs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs), in 81 breast milk samples from breastfeeding mothers from Santiago de Compostela (north-western Spain). For most detected organic pollutants, levels were correlated with the season of milk sampling, maternal age at delivery, and place of residence. Dietary consumption habits (eggs, molluscs, and vegetable oils) were also correlated with OCP, OPP, PCB, PBDE and PYR levels. We also assessed the risk to infant health of exposure to organic pollutants in breast milk. PAHs, OCPs, OPPs, and PYRs accounted for almost 95% of the targeted organic pollutants in the samples analysed.
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Contaminantes Ambientales , Hidrocarburos Clorados , Plaguicidas , Bifenilos Policlorados , Lactante , Embarazo , Femenino , Humanos , Contaminantes Ambientales/análisis , Plaguicidas/análisis , España , Compuestos Organofosforados/análisis , Bifenilos Policlorados/análisis , Hidrocarburos Clorados/análisis , Leche Humana/química , Éteres Difenilos Halogenados/análisis , Exposición MaternaRESUMEN
BACKGROUND: Hereditary fructose intolerance (HFI) is a rare inborn error of fructose metabolism caused by the deficiency of aldolase B. Since treatment consists of a fructose-, sucrose- and sorbitol-restrictive diet for life, patients are at risk of presenting vitamin deficiencies. Although there is no published data on the status of these vitamins in HFI patients, supplementation with vitamin C and folic acid is common. Therefore, the aim of this study was to assess vitamin C and folate status and supplementation practices in a nationwide cohort of HFI patients. METHODS: Vitamin C and folic acid dietary intake, supplementation and circulating levels were assessed in 32 HFI patients and 32 age- and sex-matched healthy controls. RESULTS: Most of the HFI participants presented vitamin C (96.7%) and folate (90%) dietary intake below the recommended population reference intake. Up to 69% received vitamin C and 50% folic acid supplementation. Among HFI patients, 15.6% presented vitamin C and 3.1% folate deficiency. The amount of vitamin C supplementation and plasma levels correlated positively (R = 0.443; p = 0.011). Interestingly, a higher percentage of non-supplemented HFI patients were vitamin C deficient when compared to supplemented HFI patients (30% vs. 9.1%; p = 0.01) and to healthy controls (30% vs. 3.1%; p < 0.001). CONCLUSIONS: Our results provide evidence for the first time supporting vitamin C supplementation in HFI. There is great heterogeneity in vitamin supplementation practices and, despite follow-up at specialised centres, vitamin C deficiency is common. Further research is warranted to establish optimal doses of vitamin C and the need for folic acid supplementation in HFI.
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Intolerancia a la Fructosa , Humanos , Intolerancia a la Fructosa/inducido químicamente , Ácido Fólico , Ácido Ascórbico , Vitaminas , Fructosa , Vitamina B 12RESUMEN
INTRODUCTION: MODY probability calculator (MPC) represents an easy-to-use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early-onset monogenic diabetes. METHODS: This single-centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort. RESULTS: Seventy-three individuals were included according to inclusion criteria: 20 glucokinase (GCK-MODY); 16 hepatocyte nuclear factor 1A (HNF1A-MODY); 2 hepatocyte nuclear factor 4A (HNF4A-MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes-positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%-85%). In our cohort, the best cut-off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively. CONCLUSIONS: In a highly pre-selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut-off of 36%. Further geographical and population adjustments are warranted for general use.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Glucoquinasa/genética , Humanos , Probabilidad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To characterize the longitudinal natural history of disease progression in pediatric subjects affected with mucopolysaccharidosis (MPS) IIIB. STUDY DESIGN: Sixty-five children with a confirmed diagnosis of MPS IIIB were enrolled into 1 of 2 natural history studies and followed for up to 4 years. Cognitive and adaptive behavior functions were analyzed in all subjects, and volumetric magnetic resonance imaging analysis of liver, spleen, and brain, as well as levels of heparan sulfate (HS) and heparan sulfate nonreducing ends (HS-NRE), were measured in a subset of subjects. RESULTS: The majority of subjects with MPS IIIB achieved an apex on both cognition and adaptive behavior age equivalent scales between age 3 and 6 years. Development quotients for both cognition and adaptive behavior follow a linear trajectory by which subjects reach a nadir with a score <25 for an age equivalent of 24 months by age 8 years on average and by 13.5 years at the latest. All tested subjects (n = 22) had HS and HS-NRE levels above the normal range in cerebrospinal fluid and plasma, along with signs of hepatomegaly. Subjects lost an average of 26 mL of brain volume (-2.7%) over 48 weeks, owing entirely to a loss of cortical gray matter (32 mL; -6.5%). CONCLUSIONS: MPS IIIB exists along a continuum based on cognitive decline and cortical gray matter atrophy. Although a few individuals with MPS IIIB have an attenuated phenotype, the majority follow predicted trajectories for both cognition and adaptive behavior. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02493998, NCT03227042, and NCT02754076.
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Mucopolisacaridosis III , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Gris , Heparitina Sulfato , Humanos , Imagen por Resonancia Magnética , Mucopolisacaridosis III/diagnósticoRESUMEN
Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97/268 patients), with a diagnostic turnaround time of 4-6 weeks. Most diagnoses corresponded to muscular dystrophies/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes, TTN, RYR1, and ANO5, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.
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Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 to 81 ± 51 µmol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals ≥ 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.
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Homocistinuria , Trastornos Psicóticos , Betaína/efectos adversos , Cistationina betasintasa , Homocisteína , Homocistinuria/tratamiento farmacológico , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/deficiencia , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Espasticidad MuscularRESUMEN
Perinatal Palliative Care is a model of care designed to prevent and treat the physical, spiritual, emotional, and social needs of fetuses and newborn infants with life-threatening or life-limiting conditions. The care extends to the infant's family. It is delivered by an interdisciplinary team to improve the quality of life from the time of diagnosis (possibly in utero) into death and bereavement (days, months or years later). To guarantee the access of this vulnerable population to high quality palliative care, structured programs and protocols need to be further developed in tertiary hospitals that treat highly complex obstetric and neonatal pathologies. Basic training is required for all the professionals involved.
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Aflicción , Cuidados Paliativos , Niño , Femenino , Humanos , Lactante , Recién Nacido , Atención Perinatal , Embarazo , Calidad de VidaRESUMEN
Introduction: Technological advances over the last 2 decades have led to an increase in the time spent by children and youth engaged in screen-based activities, and growing recognition of deleterious effects on health. In this systematic review of cohort and cross-sectional studies, we assess current data on the relationship between screen time and bone status in children and teenagers. Methods: We searched PUBMED and SCOPUS databases for studies of children and adolescents that assessed screen time and bone status, determined by measuring bone mineral content or density, bone stiffness index, bone speed of sound, bone broadband ultrasound attenuation, or frame index. Searches were limited to studies published between 1900 and 2020, and performed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The studies included were evaluated using the Newcastle-Ottawa quality assessment scale. Results: Ten cohort and cross-sectional studies including pediatric population were selected. The combined study population was 20,420 children/adolescents, of whom 18,444 participated in cross-sectional studies. Four studies assessed the effects of total screen time, seven the consequences of TV viewing time, and six the effects of recreational computer use on bone health. Our findings indicate an inverse association between total and weekly screen time and bone health in children and adolescents. In 57% of the studies included also a negative correlation between television viewing time and bone status was observed, while recreational computer time did not have a significant impact on bone health. According to the only four studies that included dietetic factors, no relevant differences were found between calcium intake and screen time or bone broadband ultrasound attenuation and bone speed of sound. Conclusions: Review of the literature of the past three decades provides strong support for comprehensive education of screen time on bone status. The findings of this systematic review support a negative association between screen time and bone status in children and adolescents, with a different impact when considering the different technological devices. As peak bone mass in adolescents is the strongest predictor of osteoporosis risk, strategies aimed at improving bone health should incorporate conscious use of digital technology.
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The accretion of adequate mineral content is essential for normal bone mineralization [...].
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Calcificación Fisiológica , Calcio/metabolismo , Fósforo/metabolismo , Humanos , Recién Nacido , Recien Nacido Prematuro/metabolismoRESUMEN
BACKGROUND: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). RESULTS: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5-40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106-136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03-2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68-3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25-2.34) versus 2.25 (1.62-3.00) in patients not treated with ERT. CONCLUSIONS: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams.
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Luxación de la Cadera , Mucopolisacaridosis IV , Adulto , Terapia de Reemplazo Enzimático , Humanos , Mucopolisacaridosis IV/tratamiento farmacológico , Calidad de Vida , Autocuidado , Adulto JovenRESUMEN
Pathogenic variants of the ADGRG1 gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous ADGRG1 variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel ADGRG1 variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.
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In the letter, Urro et al. performed a search on the sucrose, fructose and sorbitol content in the approved Sars-Cov-2 vaccines and they concluded that these vaccines can be safely administered in adults affected by Hereditary fructose intolerance.The Pfizer-BioNTech COVID-19 Vaccine is currently approved for use in adolescents ≥ 12 years and the Moderna COVID-19 vaccine is close to approval for use in children over 12 years of age. Furthermore, both vaccines have initiated clinical trials that will include infant as young as 6 months. Therefore, we considerate important to analyze the safely administration of this two vaccines in children with Hereditary fructose intolerance.