Publications by authors named "Guffon N"

Article Synopsis
  • Enzyme replacement therapy (ERT) with velmanase alfa demonstrated effectiveness and safety for up to 12 years in patients with alpha-mannosidosis based on a pooled analysis from two multicenter trials.
  • In pediatric patients, improvements in six-minute walk test (6MWT) and stair climb test (3MSCT) were observed, while adult patients showed stabilization or slight decline in performance.
  • The treatment resulted in sustained clearance of serum oligosaccharides and increased serum immunoglobulin G (IgG) levels, with most adverse events being mild to moderate in severity, indicating that velmanase alfa is generally well-tolerated.
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Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked, heterogeneous lysosomal storage disease. Approximately two-thirds of patients develop cognitive impairment, which is difficult to assess in clinical trials, partly owing to the variable nature of cognitive impairment. Analyzing data from siblings can help to minimize this heterogeneity.

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Article Synopsis
  • Acid sphingomyelinase deficiency (ASMD) is a serious genetic disease that can affect people from childhood to adulthood, caused by problems with a gene called SMPD1.
  • A study reviewed medical records from 27 hospitals in France to learn more about the health and survival of patients with ASMD from 1990 to 2020.
  • The results showed that patients with type A usually did not live past early childhood, while those with type B lived longer, but there were still risks of early death from serious illnesses like neurodegeneration and cancer.
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Introduction: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM.

Methods: A modified Delphi method involving 3 rounds of online surveys was used.

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Article Synopsis
  • Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease, and this study aimed to understand its natural history in children and adolescents.
  • The research included 18 patients from European centers, focusing on their medical conditions and treatments before any intervention, with a median diagnosis age of 2.5 years and a follow-up period of 10 years.
  • Common health issues reported included liver and spleen problems, frequent hospitalizations, and various surgical and infection-related events, aligning with existing literature on ASMD.
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Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler-Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry.

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Since the identification of the first disorder of mitochondrial fatty acid oxidation defects (FAOD) in 1973, more than 20 defects have been identified. Although there are some differences, most FAOD have similar clinical signs, which are mainly due to energy depletion and toxicity of accumulated metabolites. However, some of them have an unusual clinical phenotype or specific clinical signs.

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Article Synopsis
  • - Alpha-mannosidosis (AM) is a rare genetic disorder caused by the deficiency of an enzyme, leading to the buildup of certain sugars, with symptoms that can be severe and often go undiagnosed until late childhood.
  • - Velmanase alfa (VA) is the first enzyme replacement therapy approved in Europe for treating non-neurological symptoms of AM, with research suggesting earlier treatment could lead to better outcomes.
  • - A phase 2 study involving five children under 6 years old found that long-term VA treatment was generally safe, well-tolerated, and resulted in improvements in health indicators, although the small sample size limits broader conclusions.
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Background: Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi).

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Background: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage diseases caused by defective enzyme activity involved in the catalysis of glycosaminoglycans. Published data on adult patients with MPS remains scarce. Therefore, the present qualitative survey study was aimed at understanding knowledge of the disease, unmet needs, expectations, care, and overall medical management of adult/adolescent patients with MPS I, II and VI and their caregivers in France.

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Background: Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12-17 year], nine children [6-11 year], and seven infants/early child [1-5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DL), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores.

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Objective: 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.

Study Design: This cross-sectional study included mothers and/or fathers of children < 18 years of age affected by IEMs requiring a restricted diet (except phenylketonuria) from January 2015 to December 2017. Parents' QoL was assessed using the World Health Organization Quality of Life BREF questionnaire and compared with age- and sex-matched reference values from the French general population.

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Article Synopsis
  • The Morquio A Registry Study (MARS) is an ongoing international study that aims to understand the disease's variety and the long-term effects of elosulfase alfa enzyme replacement therapy (ERT) for patients with MPS IVA.
  • As of February 2021, 381 patients from 17 countries participated, with ERT-treated individuals generally diagnosed at a younger age and showing significant reductions in urinary keratan sulfate levels after treatment.
  • While nearly half of the ERT-treated subjects experienced adverse events, the study provides important data on treatment safety and effectiveness, making it the largest study of its kind for MPS IVA patients.
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Two-thirds of patients with mucopolysaccharidosis II (MPS II; Hunter syndrome) have cognitive impairment. This phase 2/3, randomized, controlled, open-label, multicenter study (NCT02055118) investigated the effects of intrathecally administered idursulfase-IT on cognitive function in patients with MPS II. Children older than 3 years with MPS II and mild-to-moderate cognitive impairment (assessed by Differential Ability Scales-II [DAS-II], General Conceptual Ability [GCA] score) who had tolerated intravenous idursulfase for at least 4 months were randomly assigned (2:1) to monthly idursulfase-IT 10 mg (n = 34) via an intrathecal drug delivery device (IDDD; or by lumbar puncture) or no idursulfase-IT treatment (n = 15) for 52 weeks.

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Enzyme replacement therapy with weekly infused intravenous (IV) idursulfase is effective in treating somatic symptoms of mucopolysaccharidosis II (MPS II; Hunter syndrome). A formulation of idursulfase for intrathecal administration (idursulfase-IT) is under investigation for the treatment of neuronopathic MPS II. Here, we report 36-month data from the open-label extension (NCT02412787) of a phase 2/3, randomized, controlled study (HGT-HIT-094; NCT02055118) that assessed the safety and efficacy of monthly idursulfase-IT 10 mg in addition to weekly IV idursulfase on cognitive function in children older than 3 years with MPS II and mild-to-moderate cognitive impairment.

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Mucopolysaccharidosis Type I (MPS I) is caused by deficiency of α-L-iduronidase. Short stature and growth deceleration are common in individuals with the attenuated MPS I phenotype. Study objectives were to assess growth in individuals with attenuated MPS I enrolled in The MPS I Registry while untreated and after initiation of enzyme replacement therapy (ERT) with laronidase (recombinant human iduronidase).

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Acid sphingomyelinase deficiency (ASMD) is a rare inherited lipid storage disorder caused by a deficiency in lysosomal enzyme acid sphingomyelinase which results in the accumulation of sphingomyelin, predominantly within cells of the reticuloendothelial system located in numerous organs, such as the liver, spleen, lungs, and central nervous system. Although all patients with ASMD share the same basic metabolic defect, a wide spectrum of clinical presentations and outcomes are observed, contributing to treatment challenges. While infantile neurovisceral ASMD (also known as Niemann-Pick disease type A) is rapidly progressive and fatal in early childhood, and the more slowly progressive chronic neurovisceral (type A/B) and chronic visceral (type B) forms have varying clinical phenotypes and life expectancy.

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Article Synopsis
  • - Mucopolysaccharidosis (MPS) disorders are rare diseases caused by enzyme deficiencies leading to the buildup of glycosaminoglycans (GAGs), with current enzyme replacement therapy (ERT) showing limited effectiveness for some systems.
  • - The Improve MPS treatment study tested the oral drug odiparcil in a Phase 2a clinical trial to evaluate its safety, pharmacokinetics, and efficacy in MPS VI patients, showing promising results in reducing GAG accumulation and improving various health aspects.
  • - The study enrolled 20 patients, with 13 completing it, and found that odiparcil increased urinary GAG levels and showed a favorable safety profile, suggesting potential benefits even in advanced disease
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Objective: 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.

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Purpose: To assess olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children.

Methods: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64.

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Introduction: Triheptanoin provides long-chain fatty acid oxidation disorder (LC-FAOD) patients with an alternative to medium-even-chain triglycerides therapy.

Material-methods: Retrospective analysis of 18 French LC-FAOD patients benefiting from early access to triheptanoin treatment.

Results: Eight female and 10 male patients with LC-FAOD (VLCAD, LCHAD, CACT, CPTII and MTP) were treated with triheptanoin for a median duration of 22 months (range: 9-228 months).

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