Publications by authors named "Lena Damaj"

Article Synopsis
  • - POLG deficiency is the most common cause of nuclear-encoded mitochondrial disorders, leading to a range of overlapping symptoms from infancy to adulthood, as seen in a study of 40 children with biallelic pathogenic variants.
  • - The study identified three main clinical patterns (neurologic, hepatic, gastrointestinal), with 24 patients requiring urgent care mainly due to severe neurologic issues like seizures and epilepsy.
  • - Most children with hepatic symptoms had the earliest onset and shortest survival rates, while those with gastrointestinal issues had milder symptoms and lived longer; overall, the prognosis was poor, with many fatalities occurring by age 10.
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Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia. It has improved response rates to chemotherapy. However, this is not without consequences.

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Objectives: Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines.

Methods: In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events.

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Primary Carnitine Deficiency (PCD) is a fatty acid oxidation disorder that will be included in the expansion of the French newborn screening (NBS) program at the beginning of 2023. This disease is of high complexity to screen, due to its pathophysiology and wide clinical spectrum. To date, few countries screen newborns for PCD and struggle with high false positive rates.

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Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available.

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X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK.

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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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Background And Purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.

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Importance: There is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).

Objectives: To report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.

Design, Setting, And Participants: The KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018.

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Article Synopsis
  • MTHFR deficiency is a serious genetic disorder affecting the body’s ability to process homocysteine, leading to severe neurological issues in infants and a lack of long-term outcome data for these patients.
  • This study analyzed clinical data from 72 MTHFR-deficient patients, focusing on those diagnosed before three months of age, to identify factors that predict severe neurodevelopmental problems.
  • Results showed that a significant percentage of early-onset patients had neurological symptoms, and those diagnosed before symptoms exhibited much better long-term outcomes, suggesting the importance of early newborn screening and treatment.
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Article Synopsis
  • * A study identified 41 patients with this specific mutation, revealing that most present CALs and freckling, while 83% meet the NIH diagnostic criteria for NF1, but there’s a significant absence of neurofibromas and gliomas, with only one documented case of a subcutaneous neurofibroma.
  • * Learning disabilities
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De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability (ID). The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n = 38) with QRICH1 variants.

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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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Article Synopsis
  • - The study aimed to improve the diagnosis of inherited ataxia and related disorders through molecular sequencing, given the complexity and variety of symptoms associated with these diseases.
  • - Researchers analyzed 366 patients with undiagnosed ataxia using clinical exome-capture sequencing and established a molecular diagnosis in 46% of cases, uncovering previously unrecognized variants.
  • - They highlighted that many patients presented with milder symptoms due to unique genetic variations like hypomorphic variants and specific mechanisms such as C-terminal truncations, identifying PEX10 and FASTKD2 as genes involved in these mild disease presentations.
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Article Synopsis
  • Complete gene deletion occurs in 5-10% of neurofibromatosis type 1 (NF1) patients, with a significant representation (4%) observed in a large French cohort of 3,479 cases.
  • A comprehensive clinical evaluation revealed that 93% of patients with gene deletion met the NIH criteria for NF1, showing a higher incidence of symptoms like café-au-lait spots, neurofibromas, and learning disabilities.
  • Compared to typical NF1 cases, the -deleted cohort displayed more severe symptoms, including a higher percentage of spinal neurofibromas, dysmorphism, and various systemic abnormalities.
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Urea cycle disorders (UCD) are rare diseases that usually affect neonates or young children. During decompensations, hyperammonemia is neurotoxic, leading to severe symptoms and even coma and death if not treated rapidly. The aim was to describe a cohort of patients with adult onset of UCDs in a multicentric, retrospective and descriptive study of French adult patients with a diagnosis after 16 years of age of UCDs due to a deficiency in one of the 6 enzymes (arginase, ASL, ASS, CPS1, NAGS, OTC) or the two transporters (ORNT1 or citrin).

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Mannose phosphate isomerase MPI-CDG (formerly CDG-1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D-mannose. We retrospectively reviewed long-term outcomes of patients with MPI-CDG, all but one of whom were treated with D-mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D-mannose treatment.

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Article Synopsis
  • TANGO2 disease is a severe genetic disorder causing symptoms like metabolic crises, brain issues, heart rhythm problems, and low thyroid hormone levels, with unclear mechanisms behind its effects.
  • A study of 20 French patients showed common symptoms include developmental delays, metabolic crises, and hypothyroidism, revealing significant variation in symptoms among families.
  • Despite normal mitochondrial function in various tests, researchers noted that TANGO2 patients might have specific triggers like certain anesthetics that lead to serious metabolic crises, indicating a need for careful cardiac and anesthesia management in treatment.
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Chronic intestinal pseudoobstruction (CIPO) is a severe form of intestinal dysmotility, and patients often undergo iterative abdominal surgeries and require parenteral nutrition. Several genes are known to be responsible for this pathology, including (autosomal dominant) and (autosomal recessive) We report the first case of unexpected trio medical exome sequencing diagnosis of mucopolysaccharidosis type I (MPS-I) in a patient with an early CIPO. There was no clinical suspicion of MPS-I at the time of the prescription.

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Objective: To describe the health status of young patients affected by inborn errors of metabolism that require adherence to a restricted diet (IEMRDs) and to describe and compare their self- and proxy (parent)-reported quality of life (QoL) with reference values.

Study Design: A cross-sectional study was conducted in 2015-2017 in patients affected by IEMRDs (except phenylketonuria) younger than 18 years. Data collection was based on medical records, clinical examinations, parents' and children's interviews, and self-reported questionnaires.

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-acetyl glutamate synthase (NAGS) deficiency is the rarest urea cycle defect presenting as neonatal onset life-threatening hyperammonemia. We report here a family history of severe NAGS deficiency: after the index-case with severe hyperammonemia, one patient benefited from antenatal diagnosis, and from primary care at birth, another one was diagnosed at 2-days and immediately treated with carbaglumic-acid. Finally, we report excellent tolerance to long-term carbaglumic-acid treatment, with no side effects, and healthy neurological and psychomotor development.

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Inborn errors of metabolism (IEM) are rare diseases caused by mutations in genes encoding enzymes or carriers. Qualitative or quantitative protein deficiency induces both an accumulation of precursor metabolites and a lack of products downstream of the blockade. Pregnancy in patients with IEM is a condition likely to promote metabolic decompensation.

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