Diagnostic Yield of Critical Sample and Elective Fast-Test in Children After a Hypoglycemic Event: Experience From a Single Center in Israel.

OBJECTIVE: To determine the diagnostic yield of the critical sample and fast-tests as dynamic function tests for the work-up of hypoglycemia in children. METHODS: A retrospective record review of children (0-18 years) with a diagnosis of hypoglycemia (glucose ≤ 50 mg/dL) was performed. A comparison of results of critical sample (obtained during an episode of hypoglycemia) and fast-test (performed to induce hypoglycemia in fasting state) was done. RESULTS: In 317 patients with hypoglycemia, data of 89 critical samples and 52 fast-tests were taken. Only 7 (7.8%) patients who underwent critical sample testing received an endocrine or metabolic diagnosis. No confirmatory diagnoses were made using the fast-tests. Idiopathic ketotic hypoglycemia was detected in 33/89 (37.1%) of critical samples and 21/52 (40.4%) of fast-tests. The completeness of workup including the hormonal and metabolic profile was <80% in both tests. CONCLUSION: The confirmatory yield of critical sample was better than fast-test. The processing of metabolic analytes was incomplete in a few, suggesting the need to rationalize the dynamic function testing.

Comparing single versus multiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT-PCR diagnostic testing.

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.

Implementing a multiplex-PCR test for the diagnosis of acute gastroenteritis in hospitalized children: Are all enteric viruses the same?

BACKGROUND: Multiplex-PCR is a valuable tool for diagnosing viral acute gastroenteritis (AGE), enabling the detection of multiple pathogens. However, distinguishing between active disease and shedding poses challenges. This study aimed to evaluate viral AGE epidemiology and compare clinical characteristics among the five most common viruses. METHODS: Rotavirus vaccine was introduced in 2010, with 70% coverage achieved in southern Israel in two years. All rectal swabs for multiplex-PCR targeting rotavirus, norovirus, adenovirus, astrovirus and sapovirus from hospitalized diarrheic children <5 years were included, from December 2017 through March 2022. Detection of the same virus within two months was considered a single episode. Clinical analysis included episodes with single-virus detection and negative bacterial PCR. RESULTS: Among 5,879 rectal swabs, 2,662 (45.3%) tested positive for at least one virus, with 245 (9.2%) showing multiple virus detection. Rotavirus was the most prevalent. While rotavirus exhibited typical winter-spring seasonality in 2018-19, an unusual off-season surge was observed during the second year of the COVID-19 pandemic. Among negative bacterial PCR episodes, 34.6% had mucus stool, 5.9% had bloody stool, and 29.3% received antibiotics. Astrovirus or sapovirus infections were associated with higher rates of hospital-acquired AGE and immunodeficiency (P<0.05), whereas rotavirus infections had higher rates of dehydration severity and acute kidney injury (P<0.05). DISCUSSION: Enteric viruses were detected in 45.3% of rectal swabs from hospitalized children with diarrhea. Despite vaccination efforts, rotavirus remained prevalent and caused more severe disease. Continuous surveillance using multiplex-PCR is crucial for accurate management and future prevention strategies for viral AGE.

The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis.

Introduction: Our aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease. Methods: A ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap. Results: A total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h). Discussion: AGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery.

GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis.

Objective: To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved. Design: Systematic review and mini meta-analysis of the literature. Methods: A search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility. Results: In total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option. Conclusions: As GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.

Novel Susceptibility Genes Drive Familial Non-Medullary Thyroid Cancer in a Large Consanguineous Kindred.

Familial non-medullary thyroid cancer (FNMTC) is a well-differentiated thyroid cancer (DTC) of follicular cell origin in two or more first-degree relatives. Patients typically demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. While known genes and chromosomal loci account for some FNMTC, the molecular basis for most FNMTC remains elusive. To identify the variation(s) causing FNMTC in an extended consanguineous family consisting of 16 papillary thyroid carcinoma (PTC) cases, we performed whole exome sequence (WES) analysis of six family patients. We demonstrated an association of ARHGEF28, FBXW10, and SLC47A1 genes with FNMTC. The variations in these genes may affect the structures of their encoded proteins and, thus, their function. The most promising causative gene is ARHGEF28, which has high expression in the thyroid, and its protein-protein interactions (PPIs) suggest predisposition of PTC through ARHGEF28-SQSTM1-TP53 or ARHGEF28-PTCSC2-FOXE1-TP53 associations. Using DNA from a patient's thyroid malignant tissue, we analyzed the possible cooperation of somatic variations with these genes. We revealed two somatic heterozygote variations in XRCC1 and HRAS genes known to implicate thyroid cancer. Thus, the predisposition by the germline variations and a second hit by somatic variations could lead to the progression to PTC.

GHRH-GH-IGF1 axis in pediatric Down syndrome: A systematic review and mini meta-analysis.

Objective: To analyze and determine the quality of functioning in different components of GHRH-GH-IGF1 axis in children with Down syndrome (DS). Design: Systematic review and mini meta-analysis of the literature. Methods: A search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included pediatric patients with DS who had undergone any laboratory evaluation of the GHRH-GH-IGF1 axis. Two reviewers independently screened articles for eligibility. Results of each type of test were weighed together in patients both with and without DS and were pooled using a random effects meta-analysis. Results: In total, 20 studies assessed the GHRH-GH-IGF1 axis function. A defect in three major components of GHRH-GH-IGF1 axis was found in a significant proportion of pediatric DS patients. Conclusions: A significant portion of short-stature pathogenesis in children with DS is associated with impaired GHRH-GH-IGF1 axis function.

Hereditary orotic aciduria identified by newborn screening.

Introduction: Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill. Methods: Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry. Results: Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the UMPS gene. Conclusion: Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.

Comparison of glucagon stimulation test and low dose ACTH test in assessing hypothalamic-pituitary-adrenal (HPA) axis in children.

INTRODUCTION: Children with a pituitary hormone deficiency are at risk for secondary adrenal insufficiency (AI). A stimulation test is usually performed for diagnosing AI, evaluating both the hypothalamic-pituitary-adrenal and growth hormone (GH)-IGF-1 axes. This single test is preferred by clinicians and is considerably more tolerable by patients. The objective of this study was to evaluate the glucagon stimulation test (GST), which is commonly used to assess both axes. Its diagnostic capability for GH deficiency is high and well accepted, however its utility for determining secondary AI has not been well established. METHODS: This retrospective study involved 120 patients under 18 years of age with short stature who had undergone both a GST and low dose ACTH stimulation test (LDACTH test). Twenty-six children who had more than 6 months elapsed between the two tests were excluded from the study. The study was conducted on patients of the Pediatric Endocrinology Department at Soroka University Hospital, a tertiary medical centre in Beer Sheva, Israel. Statistical analyses were carried out via IBM SPSS (v. 22), with a significance level determined at p < .05. RESULTS: Different cortisol cut-off values were assessed for GST and it was determined that the highest combined sensitivity and specificity yielded a cut-off point of 320 nmol/L (56% sensitivity and 83% specificity) while the currently accepted cut-off value (500 nmol/L) yielded 100% sensitivity and 6% specificity. CONCLUSION: The results of this study show that GST is not an optimal tool for diagnosing secondary AI. Therefore, clinicians using this test should interpret its results with caution.

Patterns in Body Mass Index Changes in Children after Type 1 Diabetes Mellitus Diagnosis.

BACKGROUND: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children. OBJECTIVES: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain. METHODS: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2-18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts. RESULTS: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS. CONCLUSIONS: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

The Effect of a Nutritional Supplement on Growth and Body Composition in Short and Lean Preadolescent Boys following One Year of Intervention.

INTRODUCTION: Adequate nutrition plays an important role in linear growth throughout childhood, including puberty. However, not all children are willing or able to consume an adequate and balanced diet daily. We aimed to evaluate the 1-year effectiveness and safety of nutritional supplementation on linear growth, weight gain, and changes in body composition in short and lean peripubertal boys. METHODS: A 1-year, 2-phase multicenter interventional study comprising 1-6 months of a double-blinded intervention with nutritional formula or placebo, followed by 6-12 months of an open-label extension with the nutritional formula for all participants. RESULTS: The outcomes of the double-blinded intervention were reported previously. A total of 79/98 (81%) boys, aged ≥10 years, Tanner stages 1-3, completed the open-labeled extension phase. For this phase, a significant dose-response correlation (p < 0.05) was found of the consumption of the formula with Δ height-SDS, Δ weight-SDS, and Δ muscle mass (crude correlations and after adjustment for baseline age and end-of-study Tanner stage). In the extension phase and in the 12-month analysis, participants who were good formula consumers (intake ≥50% of the recommended dose) maintained their height-SDS, while poor consumers had a significant decline in their height-SDS (p = 0.028 and p = 0.009, between group difference in the extension phase and 12-month analysis, respectively). Between-group differences were not observed in the Tanner stage at any point of the study. No serious adverse events were reported. CONCLUSIONS: An intervention in healthy peripubertal boys suggests that 1-year consumption of a multi-nutrient, protein-rich nutritional supplement is efficacious and safe. The induced changes in growth and body composition, although modest, may be clinically significant. The effect of the formula on growth parameters was not mediated by enhancement of the pubertal tempo.

Hypoparathyroidism-retardation-dysmorphism syndrome-Clinical insights from a large longitudinal cohort in a single medical center.

Background: Hypoparathyroidism, retardation, and dysmorphism (HRD) Syndrome is a rare disease composed of hypoparathyroidism, retardation of both growth and development, and distinctive dysmorphic features. Here, we describe the long-term morbidity and mortality in a large cohort of HRD patients and suggest recommendations for follow up and treatment. Methods: Medical records of 63 HRD syndrome patients who were followed at Soroka Medical Center during 1989-2019 were reviewed retrospectively. Information regarding demographics, medical complications, laboratory findings, and imaging studies was collected. Results: The mortality rate was 52%. The main causes of death were infectious diseases including pneumonia, septic shock, and meningitis. Multiple comorbidities were found including brain anomalies in 90% of examined patients (basal ganglia calcifications, tightening of corpus callosum, Chiari malformation, hydrocephalous, and brain atrophy), seizures in 62%, nephrocalcinosis and/or nephrolithiasis in 47%, multiple eye anomalies were recorded in 40%, bowel obstructions in 9.5%, and variable expression of both conductive and senso-neural hearing loss was documented in 9.5%. Conclusion: HRD is a severe multisystem disease. Active surveillance is indicated to prevent and treat complications associated with this rare syndrome.

P450 oxidoreductase regulates barrier maturation by mediating retinoic acid metabolism in a model of the human BBB.

The blood-brain barrier (BBB) selectively regulates the entry of molecules into the central nervous system (CNS). A crosstalk between brain microvascular endothelial cells (BMECs) and resident CNS cells promotes the acquisition of functional tight junctions (TJs). Retinoic acid (RA), a key signaling molecule during embryonic development, is used to enhance in vitro BBB models' functional barrier properties. However, its physiological relevance and affected pathways are not fully understood. P450 oxidoreductase (POR) regulates the enzymatic activity of microsomal cytochromes. POR-deficient (PORD) patients display impaired steroid homeostasis and cognitive disabilities. Here, we used both patient-specific POR-deficient and CRISPR-Cas9-mediated POR-depleted induced pluripotent stem cell (iPSC)-derived BMECs (iBMECs) to study the role of POR in the acquisition of functional barrier properties. We demonstrate that POR regulates cellular RA homeostasis and that POR deficiency leads to the accumulation of RA within iBMECs, resulting in the impaired acquisition of TJs and, consequently, to dysfunctional development of barrier properties.

Youth-onset type 2 diabetes in Israel: A national cohort.

BACKGROUND: Prevalence of youth-onset type 2 diabetes (T2D) has increased worldwide, paralleling the rise in pediatric obesity. Occurrence and clinical manifestations vary regionally and demographically. OBJECTIVES: We assessed the incidence, and clinical and demographic manifestations of youth-onset T2D in Israel. METHODS: In a national observational study, demographic, clinical, and laboratory data were collected from the medical records of children and adolescents, aged 10-18 years, diagnosed with T2D between the years 2008 and 2019. RESULTS: The incidence of youth-onset T2D in Israel increased significantly from 0.63/100,000 in 2008 to 3.41/100,000 in 2019. The study cohort comprised 379 individuals (228 girls [59.7%], 221 Jews [58.3%], mean age 14.7 ± 1.9 years); 73.1% had a positive family history of T2D. Mean body mass index (BMI) z-score was 1.96 ± 0.7, higher in Jews than Arabs. High systolic (≥ 130 mmHg) and diastolic blood pressure (≥ 85 mmHg) were observed in 33.7% and 7.8% of patients, respectively; mean glycosylated hemoglobin (A1c) level at diagnosis was 8.8 ± 2.5%. Dyslipidemia, with high triglyceride (>150 mg/dl) and low HDL-c (<40 mg/dl) levels, was found in 45.6% and 56.5%, respectively. Microalbuminuria and retinopathy were documented at diagnosis, 15.2% and 1.9%, respectively) and increased (36.7% and 4.6%, respectively) at follow-up of 2.9 ± 2.1 years. Criteria of metabolic syndrome were met by 224 (62.2%) patients, and fatty liver documented in 65%, mainly Jews. Psychosocial comorbidity was found in 31%. Treatment with metformin (45.6%), insulin (20.6%), and lifestyle modification (18%) improved glycemic control. CONCLUSION: Youth-onset T2D in Israel has increased significantly and presents a unique profile.

Delayed Neuropsychiatric Sequel Following Pediatric Carbon Monoxide Poisoning: A Case Report and Literature Review.

Carbon monoxide (CO) poisoning is a serious health problem. The main pathophysiological mechanism of acute CO poisoning is hypoxia due to the formation of carboxyhemoglobin (COHb). Delayed neuropsychiatric sequel (DNPS) occurs following an interval of several days to several weeks post-CO exposure and can present in many different manifestations, ranging from behavioral and mood disorders to encephalopathy and seizures and cause long-term neuropsychiatric sequel. The pathogenesis of DNPS following CO poisoning is a complex one that encompasses hypoxia-induced encephalopathy as well as inflammation, direct cellular changes and damage. The incidence varies and treatment is debated. We display a case of a previously healthy 13-year-old boy suffering from DNPS, presenting with seizures and encephalopathy and later developing optic nerve damage. Increased awareness to this condition might help diagnose future patients and aid in the understanding of the pathogenesis and treatment options for this poorly understood condition.

Does gender affect the driving performance of young patients with diabetes?

Recent evidence suggests that poor glycemic control among young patients with type 1 diabetes mellitus (T1DM) has negative cognitive and physical effects, whose extent is gender-dependent. For example, female patients with diabetes present more physical and cognitive limitations than male patients in terms of cognitive adjustment, quality of decision making, and functioning. Studies about traffic safety report that diabetic drivers are at increased risk of being involved in road crashes, especially when driving in a state of hypoglycemia under which their blood glucose level is too low. We have recently demonstrated that acute hyperglycemia (when the blood glucose level is too high) can also lead to poor driving performance among T1DM young adult patients. Against this background, the objective of the present study was to find out whether gender affects the driving performance of young drivers with diabetes. Twenty-six T1DM drivers participated in a counterbalanced crossover experiment. While being monitored by an eye tracker, they drove a driving simulator and twice navigated through the nine hazardous scenarios: once under a normal blood glucose (euglycemia) level and once high blood glucose (hyperglycemia) level. The first main result is that young female drivers are more affected by diabetes than young male drivers, regardless of momentary glycemic changes. The second main result is that poor glycemic control substantially deteriorates hazard perception and driving performance of young males with diabetes. Thus, it is argued that an uncontrolled state of a high blood glucose level may be more hazardous for young males with diabetes since it negatively impacts their driving performance.

TSHB R75G is a founder variant and prevalent cause of low or undetectable TSH in Indian Jews.

Objective: Bi-allelic loss-of-function mutations in TSHB, encoding the beta subunit of thyroid-stimulating hormone (TSH), cause congenital hypothyroidism. Homozygosity for the TSHB p.R75G variant, previously described in South Asian individuals, does not alter TSH function but abrogates its detection by some immune detection-based platforms, leading to erroneous diagnosis of hyperthyroidism. We set out to identify and determine the carrier rate of the p.R75G variant among clinically euthyroid Bene Israel Indian Jews, to examine the possible founder origin of this variant worldwide, and to determine the phenotypic effects of its heterozygosity. Design: Molecular genetic studies of Bene Israel Jews and comparative studies with South Asian cohort. Methods: TSHB p.R75G variant tested by Sanger sequencing and restriction fragment length polymorphism (RFLP). Haplotype analysis in the vicinity of the TSHB gene performed using SNP arrays. Results: Clinically euthyroid individuals with low or undetectable TSH levels from three apparently unrelated Israeli Jewish families of Bene Israel ethnicity, originating from the Mumbai region of India, were found heterozygous or homozygous for the p.R75G TSHB variant. Extremely high carrier rate of p.R75G TSHB in Bene Israel Indian Jews (~4%) was observed. A haplotype block of 239.7 kB in the vicinity of TSHB shared by Bene Israel and individuals of South Asian origin was detected. Conclusions: Our findings highlight the high prevalence of the R75G TSHB variant in euthyroid Bene Israel Indian Jews, demonstrate that heterozygosity of this variant can cause erroneous detection of subnormal TSH levels, and show that R75G TSHB is an ancient founder variant, delineating shared ancestry of its carriers.

Effect of a nutritional supplementation on growth and body composition in short and lean preadolescent boys: A randomised, double-blind, placebo-controlled study.

AIM: To evaluate the effect of nutritional supplementation on height, weight and body composition in short and lean male preadolescents. METHODS: A randomised, double-blinded, placebo-controlled trial of nutritional supplementation of short and lean prepubertal 10-14.5-year-old boys. Primary outcomes included Δheight-SDS and Δweight-SDS. Secondary outcomes included changes in body composition and BMI-SDS. RESULTS: Of 160 boys enrolled, 126 (80%) completed 6 months' intervention. Baseline age, height-SDS, weight-SDS, BMI-SDS, body composition and dietary intake were similar in the formula and placebo groups. 'Good' formula consumers (intake of ≥50% of the recommended dose, n = 30) gained significantly more in weight-SDS, BMI-SDS, fat-free-mass and muscle mass (p < 0.05) than did 'poor' consumers (n = 35) and the placebo group (n = 61). Only in the formula group, positive dose-response correlations were found between consumption of the formula and changes in the outcome parameters examined, including Δheight-SDS (r = 0.301, p = 0.015). Boys aged >11.4 years who were 'good' formula consumers maintained their Δheight-SDS, while Δheight-SDS declined in 'poor' consumers and the placebo group of the same age (p = 0.033). CONCLUSION: Intervention with a multi-nutrient, protein-rich formula was effective in increasing weight-SDS, fat-free-mass, muscle mass and BMI-SDS in short and lean prepubertal male adolescents. Good consumption of the formula prevented Δheight-SDS decline in the older participants.

The effects of the COVID-19 pandemic on patients with lysosomal storage disorders in Israel.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the causative agent of the current COVID-19 pandemic. Lysosomal storage disorders (LSD) comprise of 70 inherited inborn errors of metabolism. Affected individuals suffer from multi-systemic involvement with variable severity and rate of disease progression between different diseases. Some of the LSDs have established treatments, whether parenteral or oral therapies. The full impact of the COVID-19 pandemic together with the lockdown on the wellbeing and medical management of patients with rare diseases, such as LSDs, is widely unknown. Herein, we describe the effects of the COVID-19 pandemic and its associated mandatory home lockdown on patients with LSDs in Israel. RESULTS: We present a prospective multi-center questionnaire study including 48 LSD patients from four medical centers in Israel. The study objective was to assess the impact of the COVID-19 pandemic restrictions on individuals with LSDs in Israel, as reported by their caregivers. Secondary objectives were to assess the morbidity from SARS CoV-2 in LSD patients and the impact of changes in mood and behavior on compliance to treatment and to assess the relationship between changes in mood to changes in cognition and behavior. Thirty one of 38 patients (82%) who received any kind of regular treatment did not miss treatments. Among patients receiving enzyme replacement therapy (ERT) in the in-hospital setting, 5 patients (20%) experienced treatment disruptions. Four patients had tested positive for SARS-Cov-2 virus infection by PCR. Seven out of the 48 patients (14%) described mood changes with cognitive and motor deterioration during the home quarantine. CONCLUSIONS: We observed high rates of treatment adherence and low morbidity through the COVID-19 pandemic in patients with LSDs in Israel. LSDs patients can be a model for patients with complex chronic diseases requiring routine treatments and surveillance during a pandemic or other disruption of daily routine.