16 research outputs found
What are the clues for an inherited metabolic disorder in Reye syndrome? A single Centre study of 58 children
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Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study.
BackgroundInfants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age.ResultsNine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (nâ=â21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age â„24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious.ConclusionSebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011
Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency:an open-label, multicenter, dose-escalation study
BackgroundInfants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6Â months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6Â months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35Â mg/kg with intrapatient dose escalation up to 5Â mg/kg. The main outcome of interest is survival to 12Â months and survival beyond 24Â months of age.ResultsNine patients were enrolled; median age at baseline was 3.0Â months (range 1.1-5.8Â months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12Â months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (nâ=â21). Patients who survived to age 12Â months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15Â months of age and was related to other clinical conditions. The five surviving patients have survived to age â„24Â months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious.ConclusionSebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011
Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study
Background: Infants presenting with lysosomal acid lipase deficiency
have marked failure to thrive, diarrhea, massive hepatosplenomegaly,
anemia, rapidly progressive liver disease, and death typically in the
first 6 months of life; the only available potential treatment has been
hematopoietic stem cell transplantation, which is associated with high
morbidity and mortality in this population. The study objective was to
evaluate safety and efficacy (including survival) of enzyme replacement
with sebelipase alfa in infants with lysosomal acid lipase deficiency.
This is an ongoing multicenter, open-label, phase 2/3 study conducted in
nine countries. The study enrolled infants with growth failure prior to
6 months of age with rapidly progressive lysosomal acid lipase
deficiency; they received once-weekly doses of sebelipase alfa initiated
at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main
outcome of interest is survival to 12 months and survival beyond 24
months of age.
Results: Nine patients were enrolled; median age at baseline was 3.0
months (range 1.1-5.8 months). Sixty-seven percent (exact 95\% CI
30\%-93\%) of sebelipase alfa-treated infants survived to 12 months of
age compared with 0\% (exact 95\% CI 0\%-16\%) for a historical control
group (n = 21). Patients who survived to age 12 months exhibited
improvements in weight-for-age, reductions in markers of liver
dysfunction and hepatosplenomegaly, and improvements in anemia and
gastrointestinal symptoms. Three deaths occurred early (first few months
of life), two patients died because of advanced disease, and a third
patient died following complications of non-protocol-specified abdominal
paracentesis. A fourth death occurred at 15 months of age and was
related to other clinical conditions. The five surviving patients have
survived to age = 24 months with continued sebelipase alfa treatment;
all have displayed marked improvement in growth parameters and liver
function. Serious adverse events considered related to sebelipase alfa
were reported in one of the nine infants (infusion reaction:
tachycardia, pallor, chills, and pyrexia). Most infusion-associated
reactions were mild and non-serious.
Conclusion: Sebelipase alfa markedly improved survival with substantial
clinically meaningful improvements in growth and other key disease
manifestations in infants with rapidly progressive lysosomal acid lipase
deficienc
Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management
International audienc
Health Status of French Young Patients with Inborn Errors of Metabolism with Lifelong Restricted Diet
International audienc
Determinants of Quality of Life in Children with Inborn Errors of Metabolism Receiving a Restricted Diet
International audienceObjective To investigate the determinants of quality of life (QoL) in children with inborn errors of metabolism with restricted diet (IEMRDs) using a single theory-based multidimensional model. Study design In this multicenter cross-sectional study, data from children aged 8-17 years with IEMRDs (except phenylketonuria) and their parents were collected from January 2015 to December 2017. Measurements included a child's self-reported QoL, self-rated behavioral problems and anxiety, and parental anxiety. Based on hypotheses from a literature-built theoretical model linking demographic, clinical, family environment, and psychosocial characteristics to QoL either directly or indirectly, associations of these factors with a child's self-rated QoL were examined using a structural equation modeling approach. Results A total of 312 children (mean [SD] age, 12.2 [2.6] years; 51% boys [n = 160]) were included. Higher levels of trait anxiety and behavioral problems in children were the most important factors associated with poorer QoL (standardized path coefficients, Ă0.71 and Ă0.23, respectively). In addition, higher parent trait anxiety, younger age at diagnosis, and a disease requiring an emergency diet were associated with poorer QoL in these children. The final model fit the data closely according to conventional goodness-of-fit statistics and explained 86% of the QoL variance
Individual and Family Determinants for Quality of Life in Parents of Children with Inborn Errors of Metabolism Requiring a Restricted Diet: A Multilevel Analysis Approach
International audienceObjective The objective of this study was to compare the quality of life (QoL) for parents of children with inborn errors of metabolism (IEMs) requiring a restricted diet with French population norms and investigate parental QoL determinants
Large-scale screening of lipase acid deficiency in at risk population
International audienceBACKGROUND: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). METHODS: This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. RESULTS: LAL activity was lower than 0.05Â nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. CONCLUSION: This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations