Typical Onset Research Articles

A common benign intronic deletion masking a pathogenic deep intronic PCCB variant - genome sequencing and RNA studies to the rescue

Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by variants in PCCA or PCCB, both sub-units of the propionyl-CoA carboxylase (PCC) enzyme. PCC is required for the catabolism of certain amino acids and odd-chain fatty acids. In its absence, the accumulated toxic metabolites cause metabolic acidosis, neurologic symptoms, multi-organ dysfunction and possible death. The clinical presentation of PA is highly variable, with typical onset in the neonatal or early infantile period.We encountered two families, whose children were diagnosed with PA. Exome sequencing (ES) failed to identify a pathogenic variant, and we proceeded with genome sequencing (GS), demonstrating homozygosity to a deep intronic PCCB variant. RNA analysis established that this variant creates a pseudoexon with a premature stop codon. The parents are variant carriers, though three of them display pseudo-homozygosity due to a common large benign intronic deletion on the second allele. The parental presumed homozygosity merits special attention, as it masked the causative variant at first, which was resolved only by RNA studies.Arriving at a rapid diagnosis, whether biochemical or genetic, can be crucial in directing lifesaving care, concluding the diagnostic odyssey, and allowing the family prenatal testing in subsequent pregnancies. This study demonstrates the power of integrative genetic studies in reaching a diagnosis, utilizing GS and RNA analysis to overcome ES limitations and define pathogenicity. Importantly, it highlights that intronic deletions should be taken into consideration when analyzing genomic data, so that pseudo-homozygosity would not be misinterpreted as true homozygosity, and pathogenic variants will not be mislabeled as benign.

Washout appearance of hepatocellular carcinomas using standardized contrast-enhanced ultrasound (CEUS) including an extended late phase observation - Real-world data from the prospective multicentre DEGUM study.

Non-invasive diagnosis of hepatocellular carcinoma (HCC) in contrast-enhanced ultrasound (CEUS) is based on the combination of arterial phase hyperenhancement (APHE) and subsequent late (>60 seconds) and mild contrast washout (WO). Whereas APHE is seen in the majority of HCC, wash-out pattern may vary in onset and intensity. In some HCC lesions, even no washout is seen at all. Our prospective multicentre DEGUM HCC CEUS study aimed at identifying typical and atypical washout appearance of HCC in a real-life setting. High-risked patients for HCC with focal liver lesions upon B-mode ultrasound were recruited prospectively. In a multicentre real-life setting, a standardised CEUS examination including an extended late phase up to 6 minutes was performed. CEUS patterns of HCC were recorded, and onset and intensity of washout appearance were assessed with respect to patient and tumour characteristics. Histological findings served as reference standard. In 230/316 HCC (72.8%), a CEUS pattern of APHE followed by WO was observed. In 158 cases (68.7%), WO was typical (onset > 60 seconds, mild intensity). 72 cases (31.3%) showed marked and / or early WO, whereas in 41 HCCs (13%), APHE was followed by sustained isoenhancement.Atypical WO upon CEUS was associated with macroinvasion of the liver vessels, portal vein thrombosis and diffuse growth pattern, but not tumour size and histological grading. In a prospective multicentre real-life setting, APHE is followed by atypical washout appearance or no washout at all in almost half of the HCCs with APHE. The examiner has to bear in mind that in spite of a characteristic APHE in HCCs, washout appearance can be atypical in CEUS, especially in HCCs with macrovascular invasion or diffuse growth pattern.

The Novel Familial ST-Depression Syndrome - Current Knowledge and Perspectives.

Familial ST-depression syndrome represents a novel inherited disease characterized by nonischemic ST-segment depressions in multiple leads. The ECG phenotype appears to debut around puberty, while the typical onset of arrhythmias occurs around 50years of age. Clinical manifestations include supraventricular arrhythmias, fast polymorphic ventricular tachycardia, sudden cardiac death, and left ventricular systolic dysfunction. The optimal treatment is unknown but asymptomatic individuals without red flags may not need treatment. In contrast, ICD implantation should be considered in patients with probable arrhythmic syncope and in those fulfilling general criteria for ICD treatment. Future research should focus on establishing the disease prevalence, optimizing risk stratification and treatment, and elucidating the underlying genetic etiology.

Clinical and epidemiological features and severity markers in children admitted with multisystem inflammatory syndrome in children (MISC) in a tertiary care center in the United Arab Emirates.

Multisystem inflammatory syndrome in children (MISC) is a phenomenon that appeared in children infected with or exposed to severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2). The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response. Our study retrospectively analyzed data from a tertiary center in United Arab Emiratesof MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post-PICU admission) from May 2020 to August 2021. The total sample size was 50 patients, and the study included a comparison of MISC-PICU admissions with MISC-non-PICU admissions. The MISC-PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. MISC-PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. MISC-PICU patients presented with relatively higher inflammatory markers: C-reactive protein, procalcitonin, ferritin, and d-dimer. Immunological studies were significantly higher for interleukin-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in MISC-PICU patients. Likewise, MISC-PICU patients were provided with more extensive therapy. As part of our study course, we reevaluated our MISC-PICU patients twice, once at 48 h post-PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort. This study evaluated risk factors of MISC and potential severity features. Follow-up of patients on discharge showed improvement across all domains.

Patient-reported, health economic and psychosocial outcomes in patients with Friedreich ataxia (PROFA): protocol of an observational study using momentary data assessments via mobile health app

IntroductionFriedreich ataxia (FA) is the most common hereditary ataxia in Europe, characterised by progressively worsening movement and speech impairments with a typical onset before the age of 25 years. The...

How white matter hyperintensities impacts Alzheimer’s disease and frontotemporal dementia across underrepresented Latin American samples

AbstractBackgroundWhite matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer’s disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD.MethodA total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined.ResultTotal and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum‐hippocampus bundle in AD.ConclusionEnhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain‐specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age‐related increase in WMH.

0905 Factors Associated with Sleep Quality among Men with Multiple Sclerosis

Abstract Introduction Multiple sclerosis (MS), a neurodegenerative disease with typical onset in young to middle adulthood, results in disrupted sleep more commonly than the general population. There are known sex differences in MS onset and clinical course. MS, however, affects approximately three times more women than men, resulting in less attention to the male experience. Thus, there is a lack of information on disrupted sleep among men with MS. The purpose of this study was to examine the relationships between personal factors, behaviors, and sleep quality among men with MS. Methods Men with MS aged 20 to 90 years participated in an online anonymous survey recruited through the National MS Society website. Pearson’s correlations and linear regression were used to examine relationships between personal factors (age (years), type of MS, years since MS was diagnosed by a physician and race), sleep promoting behaviors (Sleep Behavior Self-Rating Scale), and sleep quality (Sleep Impact Short-Form total score). Results Four hundred ninety-six men with MS (mean age=53 years; SD=12.8; range 22-81 years) completed the survey. The majority were white (n=428; 86%) and married (n=358; 72%), with relapsing-remitting MS (n=323; 65%). Sleep quality ranged widely (mean=43.2; SD=3; range 27.9-59.9) with 90% reporting poor sleep. Pearson correlation results indicated a significant positive association between sleep quality and sleep promoting behaviors (r=.339) and negative associations with age (r=-234) and race (r=-.148). Multiple regression showed that sleep promoting behaviors and age statistically significantly predicted sleep quality (F(5,399) =15.51,p<.001,R2=.152). MS type, years passed since MS diagnoses and race did not add significantly to the prediction. Conclusion These findings suggest that poor sleep quality was strongly associated with sleep promoting behaviors among in older men with MS. Improving sleep promoting behaviors may substantially improve sleep quality. Further qualitative research is required to address the lack of information on understanding factors that disturb sleep among men with MS. Support (if any) This study was supported by National Heart, Lung, and Blood Institute (NHLBI) UB Clinical Scholar Program in Implementation Science to Achieve Triple Aims -NIH K12 Faculty Scholar Program in Implementation Science (NHLBI) Award

Sleep Disturbances in Early Onset Parkinsonism (P7-11.010)

<h3>Objective:</h3> To compare the frequencies of sleep disorders between individuals with early onset parkinsonism (age ≤50 at motor symptom onset) and typical onset parkinsonism (age &gt;50 at motor symptom onset). <h3>Background:</h3> Sleep disturbances are common in parkinsonian disorders and have been well-studied in individuals with parkinsonism onset after age 50. Whether sleep disorders affect individuals with early onset parkinsonism and whether they differ from individuals with typical onset parkinsonism is unknown. <h3>Design/Methods:</h3> We used a population-based, 1991 to 2015 incident-cohort study of parkinsonism including 38 patients with early onset and 1001 patients with typical onset parkinsonism. Presence or absence and type of sleep disorder as well as the relationship between motor and sleep symptoms were abstracted. Rates of sleep disorders before and after onset of parkinsonism were compared with logistic regression and Cox proportional hazards models. <h3>Results:</h3> Median (IQR) age of parkinsonism onset was 44.5 (41.0 – 48.7) years for early onset and 75.9 (67.7 – 81.7) years for typical onset patients. Parkinson’s disease (PD) was the most common cause of parkinsonism in each group. The prevalence of sleep disorders prior to the onset of parkinsonism in early vs typical parkinsonism (24% vs 16% p=0.19) and incidence of sleep disorders after parkinsonism onset (5.85 cases per 100 person-years vs 4.11 cases per 100 person-years; HR 1.15 95% CI: 0.74–1.77) were similar between the two groups, with similar latencies of sleep disorders to parkinsonism diagnosis in each group. Early onset parkinsonism had a higher risk for developing insomnia compared with typical onset parkinsonism (HR 1.73, 95% CI: 1.02 – 2.93); the risk for developing all other sleep disorders was similar between groups. <h3>Conclusions:</h3> Sleep disorders are common in individuals with early onset parkinsonism and occur with similar frequency to those with typical onset parkinsonism, except for insomnia, which was more frequent in the early onset group. <b>Disclosure:</b> Dr. McCarter has nothing to disclose. Dr. Camerucci has nothing to disclose. Aidan Mullan has nothing to disclose. Mr. Stang has nothing to disclose. Dr. Turcano has nothing to disclose. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Dr. Bower has received research support from Abbvie. The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

Myopia progression in children and adolescents: impact of COVID-19 pandemic and current and future control strategies.

Myopia is a significant and growing public health problem with typical onset or progression during childhood adolescence. High myopia has lifelong impact on ocular health and socio-economic aspects of patients 'lives. COVID-19 lockdown resulted in demonstrable increase in incidence and progression rate of myopia in children and adolescence. Low dose atropine and Orthokeratology contact lenses appear to be most effective in slowing down myopia progression. Rebound progression after stopping both modalities were reported. Defocus modifying spectacle lenses and contact lenses are less effective but possibly better tolerated.

The synaptic hypothesis of schizophrenia version III: a master mechanism.

The synaptic hypothesis of schizophrenia has been highly influential. However, new approaches mean there has been a step-change in the evidence available, and some tenets of earlier versions are not supported by recent findings. Here, we review normal synaptic development and evidence from structural and functional imaging and post-mortem studies that this is abnormal in people at risk and with schizophrenia. We then consider the mechanism that could underlie synaptic changes and update the hypothesis. Genome-wide association studies have identified a number of schizophrenia risk variants converging on pathways regulating synaptic elimination, formation and plasticity, including complement factors and microglial-mediated synaptic pruning. Induced pluripotent stem cell studies have demonstrated that patient-derived neurons show pre- and post-synaptic deficits, synaptic signalling alterations, and elevated, complement-dependent elimination of synaptic structures compared to control-derived lines. Preclinical data show that environmental risk factors linked to schizophrenia, such as stress and immune activation, can lead to synapse loss. Longitudinal MRI studies in patients, including in the prodrome, show divergent trajectories in grey matter volume and cortical thickness compared to controls, and PET imaging shows in vivo evidence for lower synaptic density in patients with schizophrenia. Based on this evidence, we propose version III of the synaptic hypothesis. This is a multi-hit model, whereby genetic and/or environmental risk factors render synapses vulnerable to excessive glia-mediated elimination triggered by stress during later neurodevelopment. We propose the loss of synapses disrupts pyramidal neuron function in the cortex to contribute to negative and cognitive symptoms and disinhibits projections to mesostriatal regions to contribute to dopamine overactivity and psychosis. It accounts for the typical onset of schizophrenia in adolescence/early adulthood, its major risk factors, and symptoms, and identifies potential synaptic, microglial and immune targets for treatment.

A One-Dimensional Blocking Index Becomes Two-Dimensional Using GIS Technology

Many previous studies of the occurrence of blocking anticyclones, their characteristics, and dynamics have defined the onset longitude using the one-dimensional zonal index type criterion proposed by Lejenas and Okland. In addition to examining the blocking event itself, the onset longitude was determined to start at the nearest five degrees longitude using the National Centers for Environmental Prediction/National Center for Atmospheric Research Reanalyses that were used to identify the events. In this study, each blocking event in the University of Missouri Blocking Archive was re-examined to identify an onset latitude, and this information was added to the archive. The events were then plotted and displayed on a map of the Northern or Southern Hemisphere using Geographic Information System (GIS) software housed at the University of Missouri as different colored and sized dots according to block intensity and duration, respectively. This allowed for a comparison of blocking events in the archive above to studies that used a two-dimensional index. Then the common onset regions were divided by phase of the El Nino and Southern Oscillation (ENSO), and the typical onset of intense and persistent blocking events could be examined. The results found a favorable comparison between the onset regions identified here and those found in previous studies that used a two-dimensional blocking index. Additionally, there was variability identified in the onset regions of blocking in both hemispheres by ENSO phase, including the location of more intense and persistent events.

Traumatic Brain Injury Triggers Neurodegeneration in a Mildly Symptomatic MELAS Patient: Implications on the Detrimental Role of Damaged Mitochondria in Determining Head Trauma Sequalae in the General Population.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited genetic mitochondrial disease with a typical onset in the first two decades of life and a major involvement of central nervous system (CNS). We present the case of a man affected with an oligosymptomatic, genetically determined MELAS syndrome, whose clinical picture dramatically and irreversibly worsened following a mild head injury. We hypothesize that the CNS metabolic stress induced by the brain injury activated an irreversible cascade of events leading to progressive neurodegeneration because damaged mitochondria were unable to restore the balance between energy requirements and availability.

Spondyloarthritides: Theories and beyond.

Spondyloarthritides (SpA) are a family of interrelated rheumatic disorders with a typical disease onset ranging from childhood to middle age. If left untreated, they lead to a severe decrease in patients' quality of life. A succesfull treatment strategy starts with an accurate diagnosis which is achieved through careful analysis of medical symptoms. Classification criterias are used to this process and are updated on a regular basis. Although there is a lack of definite knowledge on the disease etiology of SpA, several studies have paved the way for understanding plausible risk factors and developing treatment strategies. The significant increase of HLA-B27 positivity in SpA patients makes it a strong candidate as a predisposing factor and several theories have been proposed to explain HLA-B27 driven disease progression. However, the presence of HLA-B27 negative patients underlines the presence of additional risk factors. The current treatment options for SpAs are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), TNF inhibitors (TNFis), Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and physiotherapy yet there are ongoing clinical trials. Anti IL17 drugs and targeted synthetic DMARDs such as JAK inhibitors are also emerging as treatment alternatives. This review discusses the current diagnosis criteria, treatment options and gives an overview of the previous findings and theories to clarify the possible contributors to SpA pathogenesis with a focus on Ankylosing Spondylitis (AS) and enthesitis-related arthritis (ERA).

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

240 A PEDIATRIC CASE OF BIVENTRICULAR END-STAGE ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a rare heart muscle disease characterized by cardiomyocyte necrosis and fibro-adipose substitution which contribute both to the genesis of malignant ventricular arrhythmias and the morpho-functional alterations of the ventricles. ACM has always been considered a right ventricular disease with secondary involvement of the left ventricle, but recently a left dominant phenotype has been also described. Case report A 14-year-old patient was admitted to our hospital after out-of-hospital cardiac arrest due to ventricular fibrillation, which occurred when she was at rest. A family history of sudden death and dilated cardiomyopathy was retrieved (her brother died at the age of 18 with a dilated heart), but other family members had never been screened to date. Cardiac magnetic resonance imaging (cMRI) appearance was consistent with biventricular dilatation along with severe systolic dysfunction (left ventricular ejection fraction 20%; right ventricular ejection fraction 25%). It showed also thinning and bulging of the basal free wall of the right ventricle proximal to the outflow tract (up to 4 mm) and multiple foci of subepicardial, mid-wall and transmural late gadolinium enhancement (LGE) in both ventricles. Signs of acute decompensated heart failure and a high arrhythmic burden were present. After cardiopulmonary stabilization, she underwent the implantation of a cardioverter-defibrillator (ICD). Conclusion We herein report an uncommon case of biventricular AC (‘definite diagnosis’ according to both Task force criteria 2010 and Padua criteria) with advanced morpho-functional dysfunction occurring already in pediatric age, without any alerting symptom until the cardiac arrest (the typical onset of the ACM in children). It shows how severe biventricular involvement may affect young patients with a rapid progression of the disease. It also stresses the need for a strict follow-up of the family members of a proband since his first diagnosis, highlighting the pivotal role of cMRI in the diagnosis of pediatric disease. This has not been thoroughly studied and lacks sensitive and specific diagnostic criteria.

How white matter hyperintensities impacts Alzheimer's disease and frontotemporal dementia across underrepresented Latin American samples

AbstractBackgroundWhite matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer's disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD.MethodA total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined.ResultTotal and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum‐hippocampus bundle in AD.ConclusionEnhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain‐specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age‐related increase in WMH.

Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease.

Lower network segregation is associated with accelerated cognitive decline in Alzheimer's disease (AD), yet it is unclear whether less segregated brain networks facilitate connectivity-mediated tau spreading. We combined resting state functional magnetic resonance imaging (fMRI) with longitudinal tau positron emission tomography (PET) in 42 betamyloid-negative controls and 81 amyloid beta positive individuals across the AD spectrum. Network segregation was determined using resting-state fMRI-assessed connectivity among 400 cortical regions belonging to seven networks. AD subjects with higher network segregation exhibited slower brain-wide tau accumulation relative to their baseline entorhinal tau PET burden (typical onset site of tau pathology). Second, by identifying patient-specific tau epicenters with highest baseline tau PET we found that stronger epicenter segregation was associated with a slower rate of tau accumulation in the rest of the brain in relation to baseline epicenter tau burden. Our results indicate that tau spreading is facilitated by a more diffusely organized connectome, suggesting that brain network topology modulates tau spreading in AD. Higher brain network segregation is associated with attenuated tau pathology accumulation in Alzheimer's disease (AD). A patient-tailored approach allows for the more precise localization of tau epicenters. The functional segregation of subject-specific tau epicenters predicts the rate of future tau accumulation.

Eczema herpeticum and impetigo herpetiformis, is there a link?

AbstractImpetigo herpetiformis (IH) is a rare variant of pustular psoriasis with typical onset during the third trimester of pregnancy; it is characterized by erythematous plaques lined with sterile pustules and sometimes there may be systemic involvement. On the other hand, eczema herpeticum (EH) is defined as a disseminated skin infection by herpes simplex virus type 1, which mainly affects patients characterized by an impaired integrity of the skin barrier, mostly atopic dermatitis. We report the case of a 30‐year‐old woman, primigravida at 28 + 3 weeks of gestation, who after asymptomatic severe acute respiratory syndrome coronavirus 2 infection for about 7 days presented to the emergency room with a burning and itching rash on the trunk and limbs. She reported a long‐standing history of atopic dermatitis and recurrent herpetic eruptions. The diagnosis of EH was made and systemic therapy was set with excellent results. A few days later, the patient developed a pustular rash in the areas previously affected by EH, with histologic features of IH. A relation between EH and IH is thus suggested.

Newborn Screening for Sickle Cell Disease in Italy : Report of 7 Years of a Low Cost and Reproducible Program in an Area of Immigration of High Risk Population

Introduction Sickle Cell Disease (SCD) is a global health problem which presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. There are two alternative approaches to NBS. "Targeted screening" takes the ethnic ancestry of every newborn into account. Testing is restricted to babies whose parental family origins are from 'at risk' ethnic groups. In contrast, "universal screening" is offered to the whole newborn population irrespective of family origins. The area of Modena, a province of Emilia Romagna in Northern Italy, with a total population of 700,914 inhabitants, accounts for approximately 92,400 (13.2%) immigrants, mainly from sub-Saharan countries (Ghana, Nigeria, Senegal) in which SCD is endemic. The growing number of new diagnoses in children after the first years of life prompted us to design the first neonatal screening program in the province of Modena from 2011 to 2013. This pilot study allowed us to identify patients with SCD to provide as early as possible appropriate antibiotic prophylaxis, immunizations and comprehensive care. These encouraging results led us to establish a wider screening program, free of charge for the family and supported by the national health system (SSN). We describe the results of 75-year SCD newborn screening from 2015 to 2021. Methods The newborn screening program coordinated at the University Hospital of Modena involved all Obstetrics Units of the Province, taking advantage of the organization of the Italian Transfusion Medicine Departments whose mission is to study and prevent the hemolytic disease of the newborn (HDN). From January 1 2015 to December 31 2021, profile analysis of abnormal hemoglobin (Hb) by high-performance liquid chromatography (HPLC), was offered to all women within 10 weeks of pregnancy according to the Italian Guidelines for Physiological pregnancy. HPLC was also performed at delivery to the new mothers that were not tested previously ( universal screening) and to cord blood of newborns of mothers with altered hemoglobin profile (newborns at risk- target screening ). Blood samples from mother and newborns were collected daily from all maternity units of the province in EDTA (ethylendiaminetrate-acetic acid anticoagulant) and shipped to the Transfusion Medicine Departament for HDN study and then stored for 7 days at 5°C in accordance with the Italian Legislation. Results As shown in Table 1, an abnormal hemoglobin pattern was found in 2011 women and cord blood samples of their newborns at risk were tested within a week of birth . All 20 SCD ( 14 SS - 6 SC - 1 BS ) affected newborn were identified within 7 days from birth and referred immediately to pediatric hematology department of the University of Modena for early start of prophylaxis protocols and comprehensive care. The birth rate of affected infants was 0.5/1000. The current follow-up of these patients shows a significant reduction of morbidity and hospital admission compared to those who were not screened . Conclusion This is the first example of a universal screening for hemoglobinopaties involving an entire province in Italy. It allowed to start prophylaxis (amoxicillin and vaccination) for newly diagnosed SCD patients within a week after birth which is much earlier than the typical onset of disease symptoms. WHO indicates disease oriented program when the affected birth rate is about 0.5/1000.The benefit of obtaining an early diagnosis of SCD and the limited cost of the procedure support the plan of extending this reliable, simple and cost-effective screening protocol to other Italian regions/geographic areas that could be involved in migration of high-risk population for SCD . Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid,and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.