Phenotypic Expression and Outcomes in Patients with the p.Arg301Gln GLA Variant in Anderson-Fabry Disease.

The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry.

BACKGROUND: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients. METHODS: Using data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype. RESULTS: Our study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course. CONCLUSIONS: Lymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.

Wound healing activity of aqueous dispersion of fullerene C60 produced by "green technology".

In addition to exhibited antioxidant and anti-inflammatory activity, fullerene C60 is a promising wound healing agent. An important stage in the production of fullerene-based ointments is the stability of the aqueous fullerene dispersion (AFD) with minimum size of colloidal fullerene aggregates and sufficiently high concentration. To achieve these parameters tangential flow filtration of fullerene C60 was used ("green technology"). As estimated by small-angle neutron scattering and dynamic light scattering purified AFDs with narrow-size distribution nanoclusters have a size of 6 nm and are assembled into agglomerates which reach a size of 150 nm. The ability of the AFD to exhibit regenerative activity was studied using the animal wound model. This study shows for the first time that the fullerene-based composition stimulates the healing of wounds of various origins. We assume that the mechanism of the AFD wound-healing activity is associated with the aryl hydrocarbon receptor and macrophages activity.

Allele frequency deviation (AFD) as a new prognostic model to predict overall survival in lung adenocarcinoma (LUAD).

BACKGROUND: Lung adenocarcinoma (LUAD) remains one of the world's most known aggressive malignancies with a high mortality rate. Molecular biological analysis and bioinformatics are of great importance as they have recently occupied a large area in the studies related to the identification of various biomarkers to predict survival for LUAD patients. In our study, we attempted to identify a new prognostic model by developing a new algorithm to calculate the allele frequency deviation (AFD), which in turn may assist in the early diagnosis and prediction of clinical outcomes in LUAD. METHOD: First, a new algorithm was developed to calculate AFD using the whole-exome sequencing (WES) dataset. Then, AFD was measured for 102 patients, and the predictive power of AFD was assessed using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and area under the curve (AUC). Finally, multivariable cox regression analyses were conducted to evaluate the independence of AFD as an independent prognostic tool. RESULT: The Kaplan-Meier analysis showed that AFD effectively segregated patients with LUAD into high-AFD-value and low-AFD-value risk groups (hazard ratio HR = 1.125, 95% confidence interval CI 1.001-1.26, p = 0.04) in the training group. Moreover, the overall survival (OS) of patients who belong to the high-AFD-value group was significantly shorter than that of patients who belong to the low-AFD-value group with 42.8% higher risk and 10% lower risk of death for both groups respectively (HR for death = 1.10; 95% CI 1.01-1.2, p = 0.03) in the training group. Similar results were obtained in the validation group (HR = 4.62, 95% CI 1.22-17.4, p = 0.02) with 41.6%, and 5.5% risk of death for patients who belong to the high and low-AFD-value groups respectively. Univariate and multivariable cox regression analyses demonstrated that AFD is an independent prognostic model for patients with LUAD. The AUC for 5-year survival were 0.712 and 0.86 in the training and validation groups, respectively. CONCLUSION: AFD was identified as a new independent prognostic model that could provide a prognostic tool for physicians and contribute to treatment decisions.

Cardiac involvement in Lysosomal Storage Diseases.

Lysosomal storage diseases (LSDs) include a heterogeneous group of rare, inborn, metabolic diseases characterized by deficiency of lysosomal enzymes or of other proteins involved in lysosomal function, leading to multi organ system substrates accumulation, with consequent multi systemic clinical presentation. Cardiac disease is particularly important in some group of LSDs as glycogen storage diseases (Pompe), mucopolysaccharidoses and in glycosphingolipidoses (Anderson-Fabry disease and less frequently Gaucher disease). Various cardiac manifestations may be observed including hypertrophic and dilated cardiomyopathy, coronary artery disease and valvular disease. The availability of enzyme replacement therapy (ERT) has changed the natural history of some LSDs such as Pompe disease, thanks to the significant effects on cardiological involvement. In other LSDs such as MPSs or Fabry disease, ERT has been shown to stabilize or slow the progression of heart damage. This imposes the need for a timely diagnosis that allows a rapid onset of ERT.

A Symbolic Encapsulation Point as Tool for 5G Wideband Channel Cross-Layer Modeling.

Considering that networks based on New Radio (NR) technology are oriented to provide services of desired quality (QoS), it becomes questionable how to model and predict targeted QoS values, especially if the physical channel is dynamically changing. In order to overcome mobility issues, we aim to support the evaluation of second-order statistics of signal, namely level-crossing rate (LCR) and average fade duration (AFD) that is missing in general channel 5G models. Presenting results from our symbolic encapsulation point 5G (SEP5G) additional tool, we fill this gap and motivate further extensions on current general channel 5G. As a matter of contribution, we clearly propose: (i) anadditional tool for encapsulating different mobile 5G modeling approaches; (ii) extended, wideband, LCR, and AFD evaluation for optimal radio resource allocation modeling; and (iii) lower computational complexity and simulation time regarding analytical expression simulations in related scenario-specific 5G channel models. Using our deterministic channel model for selected scenarios and comparing it with stochastic models, we show steps towards higherlevel finite state Markov chain (FSMC) modeling, where mentioned QoS parameters become more feasible, placing symbolic encapsulation at the center of cross-layer design. Furthermore, we generate values within a specified 5G passband, indicating how it can be used for provisioningoptimal radio resource allocation.

The extraordinary AFD thermosensor of C. elegans.

The nematode C. elegans exhibits complex thermal experience-dependent navigation behaviors in response to environmental temperature changes of as little as 0.01°C over a > 10°C temperature range. The remarkable thermosensory abilities of this animal are mediated primarily via the single pair of AFD sensory neurons in its head. In this review, we describe the contributions of AFD to thermosensory behaviors and temperature-dependent regulation of organismal physiology. We also discuss the mechanisms that enable this neuron type to adapt to recent temperature experience and to exhibit extraordinary thermosensitivity over a wide dynamic range.

No 369 - Prise en charge de la grossesse aprés une mortinaissance.

OBJECTIF: L'objectif principal de la présente déclaration de consensus est d'élaborer des énoncés de consensus qui guideront la pratique clinique et des recommandations pour les soins prénataux et les soins intrapartum, et les considérations psychosociales dont il faut tenir compte pour prendre soin des femmes enceintes ayant des antécédents de mortinaissance. UTILISATEURS CIBLES: Les cliniciens participant à la prise en charge obstétrique des femmes ayant des antécédents de mortinaissance ou d'autres formes de décès périnatal. POPULATION CIBLE: Les femmes et les familles recevant des soins après une grossesse s'étant soldée par une mortinaissance ou une autre forme de décès périnatal. ÉVIDENCE: La présente directive clinique résume la littérature publiée et énonce un consensus général sur la prise en charge des grossesses suivant une mortinaissance ou un décès périnatal. Nous avons interrogé les bases de données MEDLINE, Embase et Cochrane au moyen des mots-clés : « previous stillbirth ¼, « perinatal loss ¼ et « subsequent pregnancy ¼. Nous avons ensuite étudié les résultats et lu les articles pertinents. Nous avons également consulté les références des articles retenus et les documents citant des études pertinentes. Les données ont ensuite été présentées pendant une réunion de consensus, et les énoncés ont été formulés. En raison du manque de données probantes, nous avons également consulté les cheminements de soins de cliniques spécialisées. VALIDATION: Le contenu et les lignes directrices ont été élaborés par les auteurs principaux en consultation avec les participants à la rencontre. Le Conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version finale avant publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interprétation des recommandations solides et conditionnelles est décrite dans le tableau 2. Le résumé des conclusions peut être fourni sur demande. AVANTAGES, INCONVéNIENTS, COûTS: Nous avons exploré une approche multidisciplinaire de prestation des soins prénataux et intrapartum aux femmes et aux familles ayant des antécédents de mortinaissance ou de décès périnatal. Bien qu'il manque de données probantes dans ce domaine, certains membres du groupe de travail fournissent ces soins à des femmes et à des familles dans plusieurs pays et nous ont fait part de leurs connaissances et de leurs expériences dans le but de guider les soins. MIS-à-JOUR: Une revue des données probantes sera menée cinq ans après la publication de la présente directive clinique afin d'évaluer si une mise à jour complète ou partielle s'impose. Cependant, si de nouvelles données probantes importantes sont publiées avant la fin du cycle de cinq ans, le processus pourrait être accéléré afin que certaines recommandations soient mises à jour rapidement. COMMANDITAIRES: La présente directive clinique a été élaborée à l'aide de ressources financées par la Société des obstétriciens et gynécologues du Canada et le Programme pour les femmes et les bébés du Centre Sunnybrook des sciences et la santé tableau 1,2. DéCLARATIONS SOMMAIRES ET RECOMMANDATIONS.

Segment-by-segment assessment of left ventricular myocardial affection in Anderson-Fabry disease by non-enhanced T1-mapping.

Background Anderson-Fabry disease (AFD) is an X-linked lysosomal enzyme disorder associated with an intracellular accumulation of sphingolipids, which shorten myocardial T1 relaxation times. Myocardial affection, however, varies between different segments. Purpose To evaluate the specific segmental distribution and degree of segmental affection in AFD patients. Material and Methods Twenty-five patients with AFD, 14 patients with hypertrophic cardiomyopathy (HCM), and 21 controls were included. A Modified Look-Locker Inversion Recovery sequence (MOLLI) was used for non-enhanced T1 mapping at 1.5 T in addition to standard cardiac imaging in 10-12 short axis views. T1 values were evaluated with a mixed model ANOVA and regression analysis to determine the best diagnostic cutoff values for T1 for each myocardial segment. Results Regression analysis showed the best diagnostic cutoff compared to controls in cardiac segments 1-4, 8-9, and 14. Mean differences between T1 for AFD versus HCM were greatest in segment 3, 4, and 9 (99 ms, 103 ms, 86 ms, respectively). Overall T1 times were 888 ± 70 ms and 903 ± 14 ms (AFD with and without LVH); 1014 ± 17 ms and 1001 ± 22 ms (HCM and controls, P < 0.05). Conclusion Myocardial segments are affected by a varying degree of T1 shortening in AFD patients. Segment-specific cutoff values allow the most specific detection and quantification of the extent of myocardial affection.

A Novel Arc Fault Detector for Early Detection of Electrical Fires.

Arc faults can produce very high temperatures and can easily ignite combustible materials; thus, they represent one of the most important causes of electrical fires. The application of arc fault detection, as an emerging early fire detection technology, is required by the National Electrical Code to reduce the occurrence of electrical fires. However, the concealment, randomness and diversity of arc faults make them difficult to detect. To improve the accuracy of arc fault detection, a novel arc fault detector (AFD) is developed in this study. First, an experimental arc fault platform is built to study electrical fires. A high-frequency transducer and a current transducer are used to measure typical load signals of arc faults and normal states. After the common features of these signals are studied, high-frequency energy and current variations are extracted as an input eigenvector for use by an arc fault detection algorithm. Then, the detection algorithm based on a weighted least squares support vector machine is designed and successfully applied in a microprocessor. Finally, an AFD is developed. The test results show that the AFD can detect arc faults in a timely manner and interrupt the circuit power supply before electrical fires can occur. The AFD is not influenced by cross talk or transient processes, and the detection accuracy is very high. Hence, the AFD can be installed in low-voltage circuits to monitor circuit states in real-time to facilitate the early detection of electrical fires.

The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice.

Moderate plant height and successful establishment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study, we characterized a rice gene, ABNORMAL FLOWER AND DWARF1 (AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull-like lodicules. AFD1 encoded a DUF640 domain protein and was expressed in all tested tissues and organs. Subcellular localization showed AFD1-green fluorescent fusion protein (GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes.

Quantification of track-weighted imaging (TWI): characterisation of within-subject reproducibility and between-subject variability.

Recently several novel image contrasts derived from whole-brain fibre tracking-data (tractograms) have been introduced. The novel contrasts of these track-weighted imaging (TWI) methods may provide important information for clinical neuroscience studies. However, before they can be used reliably to generate quantitative measures, it is important to characterise their within-subject reproducibility, and between-subject variability. In this work we compute the within-subject reproducibility (intra-scan, intra-session and inter-session), and between-subject variability of TWI for a number of different TWI contrasts across multiple subjects. The results are used in simple voxel-wise power calculations within illustrative regions of interest to provide guidelines for required sample sizes and observable effect sizes for individual subjects and between groups. It was found that the required sample sizes and observable effect sizes varied considerably between different TWI maps and for different ROIs. For some TWI contrast and ROI combinations, the power calculations yielded clinically practical values. These results provide important information concerning the potential usefulness and sensitivity of TWI maps for individual diagnosis, longitudinal studies and group comparisons, as well as for study designs.

Neuron cilia restrain glial KCC-3 to a microdomain to regulate multisensory processing.

Glia interact with multiple neurons, but it is unclear whether their interactions with each neuron are different. Our interrogation at single-cell resolution reveals that a single glial cell exhibits specificity in its interactions with different contacting neurons. Briefly, C. elegans amphid sheath (AMsh) glia apical-like domains contact 12 neuron-endings. At these ad-neuronal membranes, AMsh glia localize the K/Cl transporter KCC-3 to a microdomain exclusively around the thermosensory AFD neuron to regulate its properties. Glial KCC-3 is transported to ad-neuronal regions, where distal cilia of non-AFD glia-associated chemosensory neurons constrain it to a microdomain at AFD-contacting glial membranes. Aberrant KCC-3 localization impacts both thermosensory (AFD) and chemosensory (non-AFD) neuron properties. Thus, neurons can interact non-synaptically through a shared glial cell by regulating microdomain localization of its cues. As AMsh and glia across species compartmentalize multiple cues like KCC-3, we posit that this may be a broadly conserved glial mechanism that modulates information processing across multimodal circuits.

Feedforward and feedback mechanisms cooperatively regulate rapid experience-dependent response adaptation in a single thermosensory neuron type.

Sensory adaptation allows neurons to adjust their sensitivity and responses based on recent experience. The mechanisms that mediate continuous adaptation to stimulus history over seconds to hours long timescales, and whether these mechanisms can operate within a single sensory neuron type, are unclear. The single pair of AFD thermosensory neurons in C. elegans exhibits experience-dependent plasticity in their temperature response thresholds on both minutes- and hours-long timescales upon a temperature upshift. While long-term response adaptation requires changes in gene expression in AFD, the mechanisms driving rapid response plasticity are unknown. Here, we show that rapid thermosensory response adaptation in AFD is mediated via cGMP and calcium-dependent feedforward and feedback mechanisms operating at the level of primary thermotransduction. We find that either of two thermosensor receptor guanylyl cyclases (rGCs) alone is sufficient to drive rapid adaptation, but that each rGC drives adaptation at different rates. rGC-driven adaptation is mediated in part via phosphorylation of their intracellular domains, and calcium-dependent feedback regulation of basal cGMP levels via a neuronal calcium sensor protein. In turn, cGMP levels feedforward via cGMP-dependent protein kinases to phosphorylate a specific subunit of the cGMP-gated thermotransduction channel to further regulate rapid adaptation. Our results identify multiple molecular pathways that act in AFD to ensure rapid adaptation to a temperature change, and indicate that the deployment of both transcriptional and non-transcriptional mechanisms within a single sensory neuron type can contribute to continuous sensory adaptation.

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity.

Neurons modify their transcriptomes in response to an animal's experience. How specific experiences are transduced to modulate gene expression and precisely tune neuronal functions are not fully defined. Here, we describe the molecular profile of a thermosensory neuron pair in C. elegans experiencing different temperature stimuli. We find that distinct salient features of the temperature stimulus, including its duration, magnitude of change, and absolute value, are encoded in the gene expression program in this single neuron type, and we identify a novel transmembrane protein and a transcription factor whose specific transcriptional dynamics are essential to drive neuronal, behavioral, and developmental plasticity. Expression changes are driven by broadly expressed activity-dependent transcription factors and corresponding cis-regulatory elements that nevertheless direct neuron- and stimulus-specific gene expression programs. Our results indicate that coupling of defined stimulus characteristics to the gene regulatory logic in individual specialized neuron types can customize neuronal properties to drive precise behavioral adaptation.

Genetic screens identified dual roles of microtubule-associated serine threonine kinase and CREB within a single thermosensory neuron in the regulation of Caenorhabditis elegans thermotaxis behavior.

Animals integrate sensory stimuli presented at the past and present, assess the changes in their surroundings and navigate themselves toward preferred environment. Identifying the neural mechanisms of such sensory integration is pivotal to understand how the nervous system generates perception and behavior. Previous studies on thermotaxis behavior of Caenorhabditis elegans suggested that a single thermosensory neuron AFD plays an important role in integrating the past and present temperature information and is essential for the neural computation that drives the animal toward the preferred temperature region. However, the molecular mechanisms by which AFD executes this neural function remained elusive. Here we report multiple forward genetic screens to identify genes required for thermotaxis. We reveal that kin-4, which encodes the C. elegans homolog of microtubule-associated serine threonine kinase, plays dual roles in thermotaxis and can promote both cryophilic and thermophilic drives. We also uncover that a thermophilic defect of mutants for mec-2, which encodes a C. elegans homolog of stomatin, can be suppressed by a loss-of-function mutation in the gene crh-1, encoding a C. elegans homolog CREB transcription factor. Expression of crh-1 in AFD restored the crh-1-dependent suppression of the mec-2 thermotaxis phenotype, indicating that crh-1 can function in AFD to regulate thermotaxis. Calcium imaging analysis from freely moving animals suggest that mec-2 and crh-1 regulate the neuronal activity of the AIY interneuron, a postsynaptic partner of the AFD neuron. Our results suggest that a stomatin family protein can control the dynamics of neural circuitry through the CREB-dependent transcriptional regulation within a sensory neuron.

Temperature-Dependent Regulation of Proteostasis and Longevity.

Temperature is an important environmental condition that determines the physiology and behavior of all organisms. Animals use different response strategies to adapt and survive fluctuations in ambient temperature. The hermaphrodite Caenorhabditis elegans has a well-studied neuronal network consisting of 302 neurons. The bilateral AFD neurons are the primary thermosensory neurons in the nematode. In addition to regulating thermosensitivity, AFD neurons also coordinate cellular stress responses through systemic mechanisms involving neuroendocrine signaling. Recent studies have examined the effects of temperature on altering various signaling pathways through specific gene expression programs that promote stress resistance and longevity. These studies challenge the proposed theories of temperature-dependent regulation of aging as a passive thermodynamic process. Instead, they provide evidence that aging is a well-defined genetic program. Loss of protein homeostasis (proteostasis) is one of the key hallmarks of aging. Indeed, proteostasis pathways, such as the heat shock response and aggregation of metastable proteins, are also controlled by thermosensory neurons in C. elegans. Prolonged heat stress is thought to play a critical role in the development of neurodegenerative protein misfolding diseases in humans. This review presents the latest evidence on how temperature coordinates proteostasis and aging. It also discusses how studies of poikilothermic organisms can be applied to vertebrates and provides new therapeutic strategies for human disease.

The neural basis of heat seeking in a human-infective parasitic worm.

Soil-transmitted parasitic nematodes infect over one billion people and cause devastating morbidity worldwide. Many of these parasites have infective larvae that locate hosts using thermal cues. Here, we identify the thermosensory neurons of the human threadworm Strongyloides stercoralis and show that they display unique functional adaptations that enable the precise encoding of temperatures up to human body temperature. We demonstrate that experience-dependent thermal plasticity regulates the dynamic range of these neurons while preserving their ability to encode host-relevant temperatures. We describe a novel behavior in which infective larvae spontaneously reverse attraction to heat sources at sub-body temperatures and show that this behavior is mediated by rapid adaptation of the thermosensory neurons. Finally, we identify thermoreceptors that confer parasite-specific sensitivity to body heat. Our results pinpoint the parasite-specific neural adaptations that enable parasitic nematodes to target humans and provide the foundation for drug development to prevent human infection.

Serum Level of Alanine- and Aspartate-Aminotransferase Levels in Newborns in India.

Background: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤40 IU/L is normal. This cutoff, although determined in adults, is widely used for newborns. We studied the reference ranges for ALT and AST in newborns in India. Methods: We prospectively included babies with gestational age (GA) between 34 and 41weeks and birth weight (BW) ≥ 1500 g. We excluded the babies who either themselves or their mother had risk factors, which could cause elevation of serum levels of liver enzymes. Serum ALT and AST were measured in venous cord blood. The estimated percentile curves for ALT and AST, for BW and GA covariates, were drawn with General Additive Model for Location Scale and Shape (GAMLSS) with Box-Cox Power Exponential (BCPE). Results: Five-hundred thirty-seven babies (Boys 53.3%; GA 34-36 wks 19.7%; appropriate for GA 74.9%; BW < 2500 g 20.5%) were included. Overall, mean [SD] serum ALT and AST were 4412 IU/L and 5218 IU/L, respectively. The serum AST was significantly higher than the ALT level, regardless of gender, BW, GA, or fetal growth categories. The percentile curve against GA remained flat for ALT, although it showed a slight rise for AST. Serum levels of ALT and AST plotted against BW were also similar and showed an increase up to 2000 g and then remained stationary after that. Conclusion: The serum levels of ALT and AST up to 44 IU/L and 52 IU/L, respectively, can be taken as normal in newborns with BW ≥ 2000 g or GA ≥34 weeks.