Aromatic L-Amino Acid Decarboxylase Deficiency Is a Cause of Long-Fasting Hypoglycemia

Objective/Context: Long-fasting hypoglycemia in children may be induced by neurotransmitter disorders. Case Report: A 5-year-old girl with a medical history of chronic diarrhea presented three episodes of severe hypoglycemia (20 mg/dL) between ages 3 and 5 years. She became pale and sweaty with hypothermia (33.5°C), bradycardia (45 bpm), and acidosis and presented a generalized seizure. During the 17-hour fast test performed to determine the etiology of her hypoglycemia, insulin and C-peptide were appropriately low, and human GH, IGF-I, cortisol, amino acids, and acylcarnitines were in the usual range for fasting duration. However, the presence of vanillactic and vanilpyruvic acids in urine led us to investigate the metabolism of dopamine and serotonin in the cerebrospinal fluid. Indeed, these results indicated an aromatic L-amino acid decarboxylase deficiency that impairs the synthesis of serotonin, dopamine, and catecholamines. The diagnosis was confirmed by the low aromatic L-amino acid decarboxylase (AADC) enzyme activity in plasma (5 pmol/min/mL; reference value, 20–130) and the presence of two heterozygous mutations, c.97G>C (p.V33L, inherited from her father) and c.1385G>C (p.R462P, inherited from her mother) in the DCC gene. She was supplemented with pyridoxine and raw cornstarch (1 g/kg) at evening dinner to reduce the night fast. The episodes of hypoglycemia and the chronic diarrhea were suppressed. Conclusion: Here is the first case report of long-fasting hypoglycemia due to a nontypical AADC deficiency. Hypoglycemia was severe, but the other neurological clinical hallmarks present in AADC-deficient patients were mild to moderate. Thus, neurotransmitter disorders should be considered in any patients presenting hypoglycemia with urine excretion of vanillactic acid

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.

Inherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations. Retrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13). We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth. Overall final height (n = 69) was below target height (TH): -0.9(1.4) vs. -0.1(0.9) SD, p < 0.001. Final height was ≤ TH-2SD in 12 (21%) patients. Height ≤ - 2SD was more frequent during puberty than during early-infancy and pre-puberty: 23.5% vs. 6.9%, p = 0.002; and vs. 10.7%, p < 0.001. Pubertal delay was frequent (26.7%). Height (SD) was positively associated with isoleucine concentration: β, 0.008; 95%CI, 0.003 to 0.012; p = 0.001. In the pubertal subgroup, height (SD) was lower in patients with vs. without AAM supplementation: -1.22 (1.40) vs. -0.63 (1.46) (p = 0.02). In OA, height and median (IQR) isoleucine and valine concentrations(μmol/L) during puberty were lower in patients with vs. without AAM supplementation: -1.75 (1.30) vs. -0.33 (1.55) SD, p < 0.001; and 40 (23) vs. 60 (25) (p = 0.02) and 138 (92) vs. 191 (63) (p = 0.01), respectively. No correlation was found with IGF1. Lean-mass index was lower than fat-mass index: -2.03 (1.15) vs. -0.44 (0.89), p < 0.001. In IAAMDs, growth retardation worsened during puberty which was delayed in all disease subgroups. Height seems linked to the disease, AAM composition and lower isoleucine concentration, independently of the GH-IGF1 pathway. We recommend close monitoring of diet during puberty

Renal transplantation in 4 patients with methylmalonic aciduria: A cell therapy for metabolic disease

International audienc

Scaling of divertor power footprint width in RF-heated type-III ELMy H-mode on the EAST superconducting tokamak

Dedicated experiments for the scaling of divertor power footprint width have been performed in the ITER-relevant radio-frequency (RF)-heated H-mode scheme under the lower single null, double null and upper single null divertor configurations in the Experimental Advanced Superconducting Tokamak (EAST) under lithium wall coating conditioning. A strong inverse scaling of the edge localized mode (ELM)-averaged power fall-off width with the plasma current (equivalently the poloidal field) has been demonstrated for the attached type-III ELMy H-mode as $\lambda_{q} \propto I_{{\rm p}}^{-1.05}$ by various heat flux diagnostics including the divertor Langmuir probes (LPs), infra-red (IR) thermograph and reciprocating LPs on the low-field side. The IR camera and divertor LP measurements show that \lambda_{q,{\rm IR}} \approx {\lambda_{q,{\rm div\mbox{-}LPs}}}/{1.3}=1.15B_{{\rm p,omp}}^{-1.25} , in good agreement with the multi-machine scaling trend during the inter-ELM phase between type-I ELMs or ELM-free enhanced Dα (EDA). H-mode. However, the magnitude is nearly doubled, which may be attributed to the different operation scenarios or heating schemes in EAST, i.e., dominated by electron heating. It is also shown that the type-III ELMs only broaden the power fall-off width slightly, and the ELM-averaged width is representative for the inter-ELM period. Furthermore, the inverse Ip (Bp) scaling appears to be independent of the divertor configurations in EAST. The divertor power footprint integral width, fall-off width and dissipation width derived from EAST IR camera measurements follow the relation, λint cong λq + 1.64S, yielding $\lambda_{\rm int}^{{\rm EAST}} =(1.39\pm 0.03)\lambda_{q}^{{\rm EAST}} +(0.97\pm 0.35)\,{\rm mm}$ . Detailed analysis of these three characteristic widths was carried out to shed more light on their extrapolation to ITER

Sparse representation of signals: From astrophysics to real-time data analysis for fusion plasmas and system optimization analysis for ITER and TCV

Efficient, real-time and automated data analysis is one of the key elements for achieving scientific success in complex engineering and physical systems, two examples of which include the JET and ITER tokamaks. One problem which is common to these fields is the determination of the pulsation modes from an irregularly sampled time series. To this end, there are a wealth of signal processing techniques that are being applied to post-pulse and real-time data analysis in such complex systems. Here, we wish to present a review of the applications of a method based on the sparse representation of signals, using examples of the synergies that can be exploited when combining ideas and methods from very different fields, such as astronomy, astrophysics and thermonuclear fusion plasmas. Examples of this work in astronomy and astrophysics are the analysis of pulsation modes in various classes of stars and the orbit determination software of the Pioneer spacecraft. Two examples of this work in thermonuclear fusion plasmas include the detection of magneto-hydrodynamic instabilities, which is now performed routinely in JET in real-time on a sub-millisecond time scale, and the studies leading to the optimization of the magnetic diagnostic system in ITER and TCV. These questions have been solved by formulating them as inverse problems, despite the fact that these applicative frameworks are extremely different from the classical use of sparse representations, from both the theoretical and computational point of view. The requirements, prospects and ideas for the signal processing and real-time data analysis applications of this method to the routine operation of ITER will also be discussed. Finally, a very recent development has been the attempt to apply this method to the deconvolution of the measurement of electric potential performed during a ground-based survey of a proto-Villanovian necropolis in central Italy