Updated Iberian archeomagnetic catalogue: new full vector paleosecular variation curve for the last three millennia

In this work, we present 16 directional and 27 intensity high‐quality values from Iberia. Moreover, we have updated the Iberian archeomagnetic catalogue published more than 10 years ago with a considerable increase in the database. This has led to a notable improvement of both temporal and spatial data distribution. A full vector paleosecular variation curve from 1000 BC to 1900 AD has been developed using high‐quality data within a radius of 900 km from Madrid. A hierarchical bootstrap method has been followed for the computation of the curves. The most remarkable feature of the new curves is a notable intensity maximum of about 80 μT around 600 BC, which has not been previously reported for the Iberian Peninsula. We have also analyzed the evolution of the paleofield in Europe for the last three thousand years and conclude that the high maximum intensity values observed around 600 BC in the Iberian Peninsula could respond to the same feature as the Levantine Iron Age Anomaly, after travelling westward through Europe

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders?A successful strategy for clinical research of rare diseases

BACKGROUND: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. AIMS: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. METHODS: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. RESULTS: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (</= 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. CONCLUSIONS: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies

Decreased plasma L-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment

Background and aim: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients. Methods: We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01). Results: In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels. Conclusion: Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio

Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders

Collaborators :Hörster F, Matzkuhn H, Mütze U, Kowoll ME, Dressel M, Jelsig AM, de Lonlay P, Wijburg FA, Bosch A, Freisinger P, Jeltsch K, Posset R, Boy N, Mengler K, Augoustides-Savvopoulou P, Avram P, Deleanu C, Baumgartner MR, Häberle J, Blasco-Alonso J, Burlina AB, Rubert L, Cazorla AG, Saladelafont ECI, Dionisi-Vici C, Martinelli D, Dobbelaere D, Mention K, Grünewald S, Chakrapani A, Hwu WL, Chien YH, Lee NC, Karall D, Scholl-Bürgi S, Lachmann R, De Laet C, Matsumoto S, de Meirleir L, Mühlhausen C, Schiff M, Peña-Quintana L, Djordjevic M, Sarajlija A, Sykut-Cegielska J, Wisniewska A, Leao-Teles E, Alves S, Vara R, Vives-Pinera I, Ortega DG, Morris A, Zeman J, Honzik T, Chabrol B, Arnaudo F, Cano A, Thompson N, Eyskens F, Lindner M, Lüsebrink N, Jalan A, Sokal E, Legros V, Nassogne MC. INTRODUCTION: Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. METHOD: We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%) and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine: L-leucine: L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine and L-leucine levels lay below reference ranges in 18%, 30% and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. CONCLUSION: While MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation. This article is protected by copyright. All rights reserved