A doença de Wolman representa a manifestação mais grave da deficiência de lipase ácida lisossomal. Os fenótipos mais leves como um todo são chamados de doença de armazenamento de éster de colesterol. A enzima lipase ácida desempenha um papel essencial na hidrólise lisossomal tanto do colesterol esterificado quanto dos triglicerídeos de origem lipoproteica. Na doença de Wolman, a forma mais rara de deficiência de lipase ácida, esses lipídios se acumulam na maioria dos tecidos.
Introdução
O que você precisa saber de cara
A doença de Wolman representa a manifestação mais grave da deficiência de lipase ácida lisossomal. Os fenótipos mais leves como um todo são chamados de doença de armazenamento de éster de colesterol. A enzima lipase ácida desempenha um papel essencial na hidrólise lisossomal tanto do colesterol esterificado quanto dos triglicerídeos de origem lipoproteica. Na doença de Wolman, a forma mais rara de deficiência de lipase ácida, esses lipídios se acumulam na maioria dos tecidos.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 7 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 24 características clínicas mais associadas, ordenadas por frequência.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal recessive.
Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed:8112342, PubMed:9633819). Hydrolyzes triglycerides (1,2,3-triacylglycerol) and diglycerides (such as 1,2-diacylglycerol and 1,3-diacylglycerol) with preference for the acyl moieties at the sn-1 or sn-3 positions (PubMed:7204383, PubMed:8112342)
Lysosome
Cholesteryl ester storage disease
An autosomal recessive, mild form of lysosomal acid lipase deficiency characterized by accumulation of cholesteryl esters and triglycerides primarily in the liver. The clinical presentation is highly variable depending on residual levels of lysosomal acid lipase activity, and ranges from early onset of severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood. Age at onset varies from childhood to adulthood.
Variantes genéticas (ClinVar)
207 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 506 variantes classificadas pelo ClinVar.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
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Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Doença de Wolman
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Publicações mais relevantes
Real-World Study of Management and Outcomes of Patients with Lysosomal Acid Lipase Deficiency (LAL-D) in France.
Lysosomal acid lipase deficiency (LAL-D) is a rare inherited lysosomal storage disease leading to accumulation of lipids in organs and tissues. Severity varies from a rapidly progressive infantile form to a less severe, later-onset form. This study aimed to describe patients with LAL-D identified between 2007 and 2020, their treatment, and the burden of disease in France. A retrospective longitudinal study was conducted using nationwide claims data from the French National Health Data System (SNDS). Male and female patients were identified as having a diagnosis of LAL-D or having been administered sebelipase alfa, the only approved treatment. Of 43 patients with LAL-D identified, 17 and 26 had the infantile and later-onset forms, respectively. Frequent symptoms among infants and children included hepatomegaly, splenomegaly, and malnutrition or failure to thrive. Sebelipase alfa was administered to 10 patients with each LAL-D form. Several patients with the infantile form had hepatic complications, including portal hypertension, fibrosis, cirrhosis, and hepatic failure. Three patients, none of whom were treated with sebelipase alfa, died during the study period before the age of 2 years. The later-onset form of LAL-D was associated with hepatic complications among younger patients and cardiovascular events among older patients. Some patients with the later-onset form were treated with sebelipase alfa. Sebelipase alfa is not commercially available in France for symptomatic LAL-D in patients older than 2 years of age at disease onset; therefore, these patients may have started treatment in a clinical trial or based on a compassionate individual access. Most patients in this study were treated with lipid-lowering medications; however, several patients remained untreated. This descriptive study based on claims data confirmed the severity of LAL-D and the need to define the best management, considering the heterogeneity of the patients. Lysosomal acid lipase deficiency (LAL-D) is a rare inherited disease leading to accumulation of lipids in organs and tissues. Symptoms of the disease can appear during infancy or later. The disease is typically more severe when symptoms start in infancy, and the disease can be life-threatening if left untreated. Sebelipase alfa is the only approved treatment for LAL-D. The objective of our study was to describe patients with LAL-D in France. We identified 43 patients with LAL-D between 2007 and 2020. Of these, 17 had infantile and 26 had later-onset forms, respectively. In each group, 10 patients were treated with sebelipase alfa. Several patients with the infantile form had hepatic complications. Three of 7 patients not treated with sebelipase alfa died before the age of 2 years, whereas none of the patients treated with sebelipase alfa died. Among patients with the later-onset form, hepatic complications were observed among younger patients, whereas cardiovascular events were observed among older patients. In France, sebelipase alfa is not commercially available for patients who had first symptoms of LAL-D after 2 years of age. Patients who had symptoms of LAL-D later and were treated with sebelipase alfa may have therefore started treatment in a clinical trial or based on a compassionate individual access. Most patients in this study were treated with lipid-lowering medications; however, several patients remained untreated despite their burden, showing the need to define the best management for this disease, especially considering the heterogeneity of the patients.
Bilateral Adrenal Calcifications as an Imaging Clue to Wolman Disease in Early Infancy: A Case Report.
Wolman disease is a rare autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene, resulting in lysosomal acid lipase (LAL) deficiency and subsequent accumulation of triglycerides and cholesterol esters in multiple organs. We report the case of a two-month-old female infant with an insidious clinical course characterized by vomiting, postprandial abdominal distension, diarrhea, and failure to thrive, associated with hepatomegaly. Laboratory evaluation revealed markedly reduced total cholesterol, low-density lipoprotein, and high-density lipoprotein levels with elevated triglycerides. Abdominal ultrasound demonstrated hepatosplenomegaly with diffuse increased hepatic echogenicity consistent with steatosis and bilateral adrenal enlargement with coarse echogenic foci producing posterior acoustic shadowing, suggestive of adrenal calcifications. These findings were confirmed on contrast-enhanced abdominal computed tomography, which showed the characteristic adreniform preservation of this disease. Given the suspicion of a lysosomal storage disorder, genetic testing identified a homozygous nonsense mutation in LIPA, and enzymatic analysis confirmed markedly reduced LAL activity, establishing the diagnosis of Wolman disease. Enzyme replacement therapy was initiated, with a favorable clinical response. This case highlights the critical role of imaging findings, particularly bilateral adrenal calcifications with preserved morphology, in raising early suspicion of Wolman disease and facilitating timely diagnosis and treatment.
Best Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion.
Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. The phenotypic spectrum of lysosomal acid lipase deficiency (LAL-D) ranges from an infantile-onset form (previously known as Wolman disease) to childhood/adult-onset forms (previously known as cholesterol ester storage disease [CESD]). Infantile-onset LAL-D is rapidly progressive and symptoms arise within the first few days to weeks of life, with persistent vomiting, steatorrhea, and abdominal distention escalating (if untreated) to severe liver dysfunction and death within the first three to six months of life. However, with early diagnosis and initiation of treatment, long-term survival has improved significantly, although treated individuals may continue to have suboptimal growth, iron deficiency anemia, and lipid accumulation in the gastrointestinal mucosa. Those with infantile-onset disease who are treated typically experience normal long-term intellectual and neurodevelopmental outcomes. Individuals with childhood/adult-onset LAL-D typically present with otherwise unexplained transaminitis, organomegaly (splenomegaly and/or hepatomegaly), and liver fibrosis that can progress to cirrhosis and liver failure. Childhood/adult-onset LAL-D does not affect long-term neurodevelopmental outcome. Affected individuals typically have hyperlipidemia, especially hypercholesterolemia. There is evidence to support efficacy of enzyme replacement therapy in stabilizing progression of liver fibrosis, reducing the need for lipid-lowering medications, and potentially lowering the risk of long-term cardiovascular complications. The diagnosis of LAL-D is established in a proband with suggestive findings and biallelic pathogenic variants in LIPA identified by molecular genetic testing and/or deficient lysosomal acid lipase (LAL) enzyme activity in peripheral blood leukocytes or dried blood spots. Targeted therapies: For infantile-onset disease, enzyme replacement therapy with intravenous sebelipase alfa (premedication and desensitization protocols may be necessary) and dietary long-chain fat restriction (fat <1 g/kg/day) with supplementation of fat-soluble vitamins and essential fatty acids is recommended; some affected individuals may also benefit from hematopoietic stem cell transplantation. For childhood/adult-onset disease, intravenous administration of sebelipase alfa (1 mg/kg body weight every other week) is recommended; some centers also recommend dietary modification. Liver transplantation has been performed in individuals with adult-onset disease, especially in those with progressive liver fibrosis or cirrhosis, although there is a risk of recurrence of liver disease and it is not considered curative. Supportive care: Standard treatment for anemia/thrombocytopenia. For childhood/adult-onset disease, lipid-lowering medications for hyperlipidemia; standard treatment for cardiovascular disease, malabsorption/malnutrition, esophageal varices, and anemia/thrombocytopenia. Surveillance: For infantile-onset disease, measure weight, length/height, and mid-upper arm circumference in infants/children and weight in adults at each visit; assess for chronic diarrhea and monitor liver enzymes, essential fatty acids, and fat-soluble vitamins (A, D, E, and K) levels every six months; obtain a complete blood count every six months in children and every six to 12 months in adults to assess for anemia and thrombocytopenia; monitor anti-drug antibody (ADA) concentration for those on enzyme replacement therapy if the ALT and AST levels are >3 times the normal limit or if there are clinical concerns regarding efficacy of treatment, such as weight loss / poor weight gain, increased stool frequency, or elevated inflammatory markers (i.e., ferritin and LDH); abdominal imaging to assess the liver, spleen, and mesenteric lymph nodes and to evaluate for hepatocellular carcinoma every six to 12 months in those with advanced cirrhosis. For childhood/adult-onset disease, measure weight and length/height in infants/children and weight in adults at each visit; assess for chronic diarrhea and monitor essential fatty acids and fat-soluble vitamin (A, D, E, and K) levels with consideration of monitoring liver enzymes, chitotriosidase, ferritin, and LDH as clinically indicated; measure liver enzymes every six to 12 months or as clinically indicated based on disease severity; assess for hepatomegaly, hepatic fibrosis, and cirrhosis at every visit, as indicated by clinical/biochemical parameters; monitor anti-drug antibody (ADA) concentration as clinically indicated for those on enzyme replacement therapy; obtain a complete blood count and fasting lipid levels every six months in children and every six to 12 months (or as clinically indicated based on disease severity) in adults; upper endoscopy every three years in those with severe liver disease; abdominal imaging to assess the liver, spleen, and mesenteric lymph nodes and to evaluate for hepatocellular carcinoma as clinically indicated in those with advanced cirrhosis. Agents/circumstances to avoid: Those with thrombocytopenia should avoid use of nonsteroidal anti-inflammatory drugs. Evaluation of relatives at risk: It is appropriate to evaluate the sibs of a proband in order to identify those who would benefit from early institution of treatment. If the LIPA pathogenic variants in the family are known, molecular genetic testing can be used to clarify the genetic status of at-risk sibs; if the LIPA pathogenic variants are not known, assay of LAL enzyme activity can be used to assist in the identification of affected sibs. LAL-D is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a LIPA pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If the LIPA pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.
Overview of pediatric and adult lysosomal acid lipase deficiency: expert recommendations from a Gulf cooperation council working group.
Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive ultrarare lysosomal storage disease caused by pathogenic/likely pathogenic variants in the LIPA gene. The age of onset and progression rate can significantly vary, possibly due to the nature of the underlying variants. The disorder is often misdiagnosed or undiagnosed in the Gulf Cooperation Council (GCC) countries owing to its nonspecific clinical presentation; this necessitates establishing campaigns to increase awareness among healthcare professionals and strategies for identifying and screening high-risk populations. This narrative review is based on an analysis of the available literature, complemented by key discussions among a group of recognized healthcare professionals from the GCC region with expertise in clinical genetics, hepatology, gastroenterology, and lipidology. The outcome of their discussions is a set of practical recommendations and insights aimed at assisting physicians across multiple specialties in the identification and management of individuals affected by this ultrarare genetic disorder. LAL-D presents significant diagnostic and management challenges, particularly within the GCC region, owing to its rarity, limited awareness, and insufficient utilization of genetic testing. The prevalence and distribution of genetic variations associated with LAL-D remain inadequately explored in this population. The development of standardized regional guidelines is essential to harmonize diagnostic and management practices. Continued research efforts focusing on the genetic landscape of LAL-D in the GCC are imperative to bridge knowledge gaps and enhance clinical outcomes for affected patients.
Childhood to adult transition in youth patients with lysosomal acid lipase deficiency: 43 recommendations from experts.
The process of transition from pediatric to adult care is crucial, especially in rare diseases such as lysosomal acid lipase deficiency (LAL-D). Unfortunately, this process is associated with poor outcomes, and many challenges still await to be addressed. This document provides recommendations on the pediatric to adult care transition in patients with LAL-D, based on available evidence and the experience of a panel of experts, which include specialists in the management of patients with LAL-D, and representative patients of the AELALD patient organization. Additionally, the main uncertainties and/or challenges encountered by the different stakeholders during the process are defined. A total of 43 consensus recommendations were developed across 5 areas. The consensus recommendations reflect the personal opinions and experiences of the participating experts supported with evidence when available. Overall, the main uncertainties and/or challenges faced comprise the patient's mistrust in the new medical team, the insufficient information received, or the lack of time, resources and institutional support. The management of adolescents/young adults during the transition to adulthood should be a joint effort between the patient, clinical center, and parents/caregivers. The objective of the transition process should be to empower patients and progressively encourage the self-management of their disease, and therefore patients and their families should be involved in all phases of the transition. Facilitating elements, such as standardized protocols, arose as important tools to ease the transition process. This multidisciplinary consensus provides information on the main obstacles found by patients and their families, pediatricians and adult physicians during the transition from pediatric to adult care in LAL-D. To overcome these barriers, the scientific committee highlights the need for different facilitating elements, which include an effective collaboration between healthcare teams, the elaboration of standardized protocols, the implementation of education for patients, or the individual evaluation of the need for psychological support. The recommendations provided by the experts are the basis to facilitate and improve the transition process.
Publicações recentes
Real-World Study of Management and Outcomes of Patients with Lysosomal Acid Lipase Deficiency (LAL-D) in France.
Bilateral Adrenal Calcifications as an Imaging Clue to Wolman Disease in Early Infancy: A Case Report.
Best Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion.
Lysosomal Acid Lipase Deficiency.
Hepatic Steatosis: A Presentation of Cholesteryl Ester Storage Disease.
📚 EuropePMC91 artigos no totalmostrando 197
Real-World Study of Management and Outcomes of Patients with Lysosomal Acid Lipase Deficiency (LAL-D) in France.
Advances in therapyBilateral Adrenal Calcifications as an Imaging Clue to Wolman Disease in Early Infancy: A Case Report.
CureusBest Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion.
NutrientsHepatic Steatosis: A Presentation of Cholesteryl Ester Storage Disease.
ACG case reports journalOverview of pediatric and adult lysosomal acid lipase deficiency: expert recommendations from a Gulf cooperation council working group.
Orphanet journal of rare diseasesLong-term clinical outcomes in lysosomal acid lipase deficiency: Fibrosis regression with sebelipase alfa therapy.
Canadian liver journalSurvival, growth, and safety findings in patients with rapidly progressive, infantile-onset LAL-D: Results from the international LAL-D registry.
Molecular genetics and metabolismRapidly progressive, infantile lysosomal acid lipase deficiency: Prevalence in the Mizrahi Jewish population.
Molecular genetics and metabolismEnzyme replacement therapy in cholesteryl ester storage disease: A case report on lysosomal acid lipase deficiency management.
Journal of clinical lipidologyThe lysosomal acid lipase deficiency spectrum from infancy to adulthood: a multidisciplinary experience.
Nutrition, metabolism, and cardiovascular diseases : NMCDCholesterol Ester Storage Disease in Two Field Spaniels With Lysosomal Acid Lipase Deficiency.
Journal of veterinary internal medicineScreening for Lysosomal Acid Lipase Deficiency in a Lipid Clinic.
Arquivos brasileiros de cardiologiaSebelipase Alfa Improves Aminotransferase Levels in Lysosomal Acid Lipase Deficiency: Data From an International Registry.
Liver international : official journal of the International Association for the Study of the LiverAdvanced Imaging and Cytometric Techniques to Characterize Lipid Accumulation in Wolman Disease.
Cytometry. Part A : the journal of the International Society for Analytical CytologyChildhood to adult transition in youth patients with lysosomal acid lipase deficiency: 43 recommendations from experts.
Orphanet journal of rare diseasesThe Hidden Burden: Gastrointestinal Involvement in Lysosomal Storage Disorders.
Metabolites[Screening of high risk children for lysosomal storage diseases and analysis of disease spectrum].
Zhonghua er ke za zhi = Chinese journal of pediatricsIncidental finding of adrenal calcifications leading to the diagnosis of lysosomal acid lipasedeficiency (Wolman disease) in a neonate.
BMJ case reportsDoes Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening.
International journal of neonatal screeningPractical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease.
NutrientsLysosomal Acid Lipase Deficiency: A Report of Two Cases and a Review of the Literature.
CureusLiver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency.
Molecular therapy : the journal of the American Society of Gene TherapyLimited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.
International journal of molecular sciencesEvaluation of 73 Enlisted Patients for Liver Transplant with Unknown Etiology Reveals a Late-Diagnosed Case of Lysosomal Acid Lipase Deficiency.
International journal of molecular sciencesTwice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.
Orphanet journal of rare diseasesNeutral lipid storage disease with ichthyosis and fatty liver.
BMJ case reportsA 14-step desensitization protocol for sebelipase alfa hypersensitivity in a patient with Wolman disease and secondary hemophagocytic lymphohistiocytosis.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and ImmunologyImpaired lysosomal acidity maintenance in acid lipase-deficient cells leads to defective autophagy.
The Journal of biological chemistryHigh-Dose ERT, Rituximab, and Early HSCT in an Infant with Wolman's Disease.
The New England journal of medicineLoss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice.
Molecular metabolismDissecting cell type-specific impact in lysosomal acid lipase deficiency-associated disorders.
Journal of lipid researchPrevalence of p.G87V and p.Gln298=Variations in LIPA Gene Within Middle Eastern Population Living Around Los Angeles.
Genetic testing and molecular biomarkersWolman disease presenting with hemophagocytic lymphohistiocytosis syndrome and a novel LIPA gene variant: a case report and review of the literature.
Journal of medical case reportsMetabolic changes and propensity for inflammation, fibrosis, and cancer in livers of mice lacking lysosomal acid lipase.
Journal of lipid researchA Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant.
Archives of Iranian medicineFirst LIPA Mutational Analysis in Egyptian Patients Reveals One Novel Variant: Wolman Disease.
Journal of molecular neuroscience : MNLysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry.
Liver international : official journal of the International Association for the Study of the LiverImpact of (intestinal) LAL deficiency on lipid metabolism and macrophage infiltration.
Molecular metabolismRapid whole-genome sequencing leading to specific treatment for two infants with haemophagocytic lymphohistiocytosis due to Wolman disease.
Pediatric blood & cancerPediatric patients with lysosomal acid lipase deficiency.
Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de CitologiaEvaluation of biochemical profile and oxidative damage to lipids and proteins in patients with lysosomal acid lipase deficiency.
Biochemistry and cell biology = Biochimie et biologie cellulaireRecent insights into lysosomal acid lipase deficiency.
Trends in molecular medicineLAL deficiency induced myeloid-derived suppressor cells as targets and biomarkers for lung cancer.
Journal for immunotherapy of cancerA Novel Variant in the LIPA Gene Associated with Distinct Phenotype.
Balkan journal of medical genetics : BJMGRare diseases presenting with hemophagocytic lymphohistiocytosis.
Pediatrics international : official journal of the Japan Pediatric SocietyOutcome of haematopoietic cell transplantation in children with lysosomal acid lipase deficiency: a study on behalf of the EBMT Inborn Errors Working Party.
Bone marrow transplantationStructure-based virtual screening to identify potential lipase inhibitors to reduce lipid storage in Wolman disorder.
Advances in protein chemistry and structural biologyLysosomal Acid Lipase Deficiency: Genetics, Screening, and Preclinical Study.
International journal of molecular sciencesStratification of patients with lysosomal acid lipase deficiency by enzyme activity in dried blood spots.
Molecular genetics and metabolism reportsNatural history and management of liver dysfunction in lysosomal storage disorders.
World journal of hepatologyLysosomal Acid Lipase Activity in Non-alcoholic Fatty Liver Disease as a Novel Diagnostic and Therapeutic Target: A Systematic Literature Review of Current Evidence and Future Directions.
Journal of clinical and experimental hepatologyCould lysosomal acid lipase enzyme activity be used for clinical follow-up in cryptogenic cirrhosis?
Turkish journal of medical sciencesLysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease.
Frontiers in geneticsEarly diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five.
Canadian liver journal15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report.
MedicineTherapeutic efficacy of rscAAVrh74.miniCMV.LIPA gene therapy in a mouse model of lysosomal acid lipase deficiency.
Molecular therapy. Methods & clinical developmentLC-MS/MS-based enzyme assay for lysosomal acid lipase using dried blood spots.
Molecular genetics and metabolism reportsClinical insights from Wolman disease: Evaluating infantile hepatosplenomegaly.
American journal of medical genetics. Part ADrosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.
Frontiers in agingRapid whole genome sequencing of critically ill pediatric patients from genetically underrepresented populations.
Genome medicineLessons Learned From the Long-Term Use of Enzyme Replacement Therapy in the Treatment of Lysosomal Acid Lipase Deficiency.
Journal of pediatric gastroenterology and nutrition"Why them, why me, why us?" The experiences of parents of children with lysosomal acid lipase deficiency: an interpretative phenomenological analysis study.
Orphanet journal of rare diseasesLiving-Donor Liver Transplantation for Late-Onset Lysosomal Acid Lipase Deficiency.
Journal of clinical and experimental hepatologyOff-target effects of the lysosomal acid lipase inhibitors Lalistat-1 and Lalistat-2 on neutral lipid hydrolases.
Molecular metabolismLong-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency.
Journal of pediatric gastroenterology and nutritionDiagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis.
Molecular genetics and metabolism reportsNovel association of metastatic Crohn's disease and Wolman disease.
JAAD case reportsLysosomal acid lipase promotes endothelial proliferation in cold-activated adipose tissue.
AdipocyteA rare case of lysosomal acid lipase deficiency diagnosed by endoscopy.
Gastrointestinal endoscopySebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up.
Orphanet journal of rare diseases[Disturbance of lipid homeostasis in lysosomal lipase deficiency – pathomechanism, diagnosis and treatment].
Postepy biochemiiSebelipase alfa in children and adults with lysosomal acid lipase deficiency: Final results of the ARISE study.
Journal of hepatologySafety of sebelipase alfa for the treatment of lysosomal acid lipase deficiency.
Expert opinion on drug safetyDefective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth.
International journal of molecular sciencesMolecular markers of brain cholesterol homeostasis are unchanged despite a smaller brain mass in a mouse model of cholesteryl ester storage disease.
LipidsEffect of a common missense variant in LIPA gene on fatty liver disease and lipid phenotype: New perspectives from a single-center observational study.
Pharmacology research & perspectivesHormone-sensitive lipase deficiency affects the expression of SR-BI, LDLr, and ABCA1 receptors/transporters involved in cellular cholesterol uptake and efflux and disturbs fertility in mouse testis.
Biochimica et biophysica acta. Molecular and cell biology of lipidsCT features of Wolman disease (lysosomal acid lipase enzyme deficiency) - A case report.
Radiology case reportsEnzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review.
Therapeutic advances in rare diseaseEnzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease.
Orphanet journal of rare diseasesLysosomal acid lipase deficiency in pediatric patients: a scoping review.
Jornal de pediatriaLarge-scale screening of lipase acid deficiency in at risk population.
Clinica chimica acta; international journal of clinical chemistryLoss of function of lysosomal acid lipase (LAL) profoundly impacts osteoblastogenesis and increases fracture risk in humans.
BoneCross-sectional imaging features of unusual adrenal lesions: a radiopathological correlation.
Abdominal radiology (New York)Secondary Hemophagocytic Lymphohistiocytosis in an Infant with Wolman Disease.
Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood TransfusionLysosomal acid lipase deficiency diagnosed in a patient presenting with acute myeloid leukaemia.
British journal of haematologyGastrointestinal Manifestations of a Rare Lipid Storage Disorder.
GastroenterologyWolman's disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review.
BMC pediatricsThe Emerging Battle: Lysosomal Acid Lipase Deficiency vs Familial Hypercholesterolemia in Children.
ACG case reports journalLong-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies.
Orphanet journal of rare diseasesA rare cause of hepatomegaly and dyslipidemia: lysosomal acid lipase deficiency.
The Turkish journal of pediatricsA Case of Lysosomal Acid Lipase Deficiency Confirmed by Response to Sebelipase Alfa Therapy.
Journal of pediatric gastroenterology and nutrition[Lysosomal acid lipase deficiency: A rarely recognised cause of dyslipidaemia and liver dysfunction].
Anales de pediatriaDiet-refractory NASH in an elderly woman.
GutSebelipase alfa for lysosomal acid lipase deficiency: 5-year treatment experience from a phase 2 open-label extension study.
Liver international : official journal of the International Association for the Study of the LiverCholestane-3β, 5α, 6β-triol: Further insights into the performance of this oxysterol in diagnosis of Niemann-Pick disease type C.
Molecular genetics and metabolismA Rare Image of Liver Steatosis - Acid Lipase Lysosomal Deficiency.
Journal of gastrointestinal and liver diseases : JGLDLysosomal Acid Lipase Deficiency: Therapeutic Options.
Drug design, development and therapyClinical and Histologic Liver Improvement in Siblings With Lysosomal Acid Lipase Deficiency After Enzyme Replacement.
Journal of pediatric gastroenterology and nutritionPersistent dyslipidemia in treatment of lysosomal acid lipase deficiency.
Orphanet journal of rare diseasesAISF update on the diagnosis and management of adult-onset lysosomal storage diseases with hepatic involvement.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the LiverInitial assessment and ongoing monitoring of lysosomal acid lipase deficiency in children and adults: Consensus recommendations from an international collaborative working group.
Molecular genetics and metabolismReduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?
World journal of gastroenterologyEarly diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy.
Orphanet journal of rare diseasesA kinetic assay of total lipase activity for detecting lysosomal acid lipase deficiency (LAL-D) and the molecular characterization of 18 LAL-D patients from Russia.
JIMD reportsLysosomal acid lipase deficiency in Brazilian children: a case series.
Jornal de pediatriaElevated Liver Enzymes in a Young Man with Hyperlipidemia.
GastroenterologyHemophagocytic Lymphohistiocytosis: A Rare Complication of an Ultrarare Lysosomal Storage Disease.
Journal of pediatric hematology/oncologyThe novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.
Molecular genetics and metabolismDeficiencia de lipasa ácida lisosomal, una patología infrecuente.
Gaceta medica de MexicoMutations identified in a cohort of Mexican patients with lysosomal acid lipase deficiency.
Annals of hepatologyLarge-scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency.
Human mutationModeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
Cell metabolismLysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation.
Annals of hepatologyA decade of excellent transplant survival in children with inherited metabolic diseases: A report from a single metabolic transplant centre in Europe.
Blood cell therapyMetabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders.
Free radical biology & medicineEvaluation of two approaches to lysosomal acid lipase deficiency patient identification: An observational retrospective study.
AtherosclerosisLysosomal Acid Lipase in Lipid Metabolism and Beyond.
Arteriosclerosis, thrombosis, and vascular biologyOpening a window on lysosomal acid lipase deficiency: Biochemical, molecular, and epidemiological insights.
Journal of inherited metabolic diseaseLysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target.
Trends in pharmacological sciencesHepatocyte-specific lysosomal acid lipase deficiency protects mice from diet-induced obesity but promotes hepatic inflammation.
Biochimica et biophysica acta. Molecular and cell biology of lipidsThe Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease.
Journal of pediatric gastroenterology and nutritionThe global prevalence and genetic spectrum of lysosomal acid lipase deficiency: A rare condition that mimics NAFLD.
Journal of hepatologyScreening for lysosomal acid lipase deficiency: A retrospective data mining study and evaluation of screening criteria.
AtherosclerosisA rare cause of hepatomegaly in the childhood: Lysosomal acid lipase deficiency.
The Turkish journal of gastroenterology : the official journal of Turkish Society of GastroenterologySuccessful sebelipase alfa desensitization in a pediatric patient.
The journal of allergy and clinical immunology. In practiceDifferential Diagnosis of a Patient with Lysosomal Acid Lipase Deficiency: A Case Report.
Laboratory medicineDiagnostic Algorithm for Cholesteryl Ester Storage Disease: Clinical Presentation in 19 Polish Patients.
Journal of pediatric gastroenterology and nutritionAdrenal Calcifications in an Infant.
The New England journal of medicineLysosomal Acid Lipase Deficiency, a Rare Pathology: The First Pediatric Patient Reported in Colombia.
The American journal of case reportsGenetically modified mouse models to study hepatic neutral lipid mobilization.
Biochimica et biophysica acta. Molecular basis of diseaseEndoscopic Findings in Lysosomal Acid Lipase Deficiency.
Journal of pediatric gastroenterology and nutritionLysosomal Acid Lipase Deficiency in Japan: A Case Report of Siblings and a Literature Review of Cases in Japan.
Journal of Nippon Medical School = Nippon Ika Daigaku zasshiEarly onset lysosomal acid lipase deficiency presenting as secondary hemophagocytic lymphohistiocytosis: Two infants treated with sebelipase alfa.
Clinics and research in hepatology and gastroenterologyA Novel Mutation c.153 C>A in a Tunisian Girl With Wolman Disease and Unusual Presentation: Hemophagocytic Lymphohistiocytosis.
Journal of pediatric hematology/oncologyLysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients.
Molecular genetics and metabolismSebelipase alfa improves atherogenic biomarkers in adults and children with lysosomal acid lipase deficiency.
Journal of clinical lipidologyLysosomal acid lipase and lipid metabolism: new mechanisms, new questions, and new therapies.
Current opinion in lipidologyBenefit of Treatment With Sebelipase-Alfa in a 63-Year-Old Patient With Advanced Liver and Atherosclerotic Disease Due to Lysosomal Acid Lipase Deficiency (LAL-D).
The American journal of gastroenterologySecondary Hemophagocytic Syndrome Associated with COG6 Gene Defect: Report and Review.
JIMD reportsHealthcare resource use and costs of managing children and adults with lysosomal acid lipase deficiency at a tertiary referral centre in the United Kingdom.
PloS oneLong term substrate reduction therapy with ezetimibe alone or associated with statins in three adult patients with lysosomal acid lipase deficiency.
Orphanet journal of rare diseasesIdentification of rare diseases by screening a population selected on the basis of routine pathology results-the PATHFINDER project: lysosomal acid lipase/cholesteryl ester storage disease substudy.
Journal of clinical pathologySpecific Substrate for the Assay of Lysosomal Acid Lipase.
Clinical chemistryLysosomal Acid Lipase Deficiency: Could Dyslipidemia Drive the Diagnosis?
Current pediatric reviewsMexican consensus on lysosomal acid lipase deficiency diagnosis.
Revista de gastroenterologia de Mexico (English)Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse.
Steroids[Lysosomal acid lipase deficiency (LAL-D) : Diagnostic and therapeutic options in an underdiagnosed disease].
Der PathologeIMPORTANCE OF LIVER BIOPSY IN THE DIAGNOSIS OF LYSOSOMAL ACID LIPASE DEFICIENCY: A CASE REPORT.
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao PauloImaging of Nonmalignant Adrenal Lesions in Children.
Radiographics : a review publication of the Radiological Society of North America, IncGenetic Testing in Liver Disease: What to Order, in Whom, and When.
Clinics in liver diseaseEndothelial Rab7 GTPase mediates tumor growth and metastasis in lysosomal acid lipase-deficient mice.
The Journal of biological chemistrySteryl ester synthesis, storage and hydrolysis: A contribution to sterol homeostasis.
Biochimica et biophysica acta. Molecular and cell biology of lipidsMolecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants.
AtherosclerosisThe role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.
Therapeutic advances in gastroenterologyWolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency.
The lancet. Gastroenterology & hepatologyNeural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.
Orphanet journal of rare diseasesLysosomal acid lipase deficiency: a form of non-obese fatty liver disease (NOFLD).
Expert review of gastroenterology & hepatologyA Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease.
International journal of molecular sciencesWolman Disease: A Mimic of Infant Leukemia.
Journal of pediatric hematology/oncologyFast progression of liver damage in lysosomal acid lipase deficiency.
Current medical research and opinionBest practice in the measurement and interpretation of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2.
Clinica chimica acta; international journal of clinical chemistryLiver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update.
Archivos argentinos de pediatriaLysosomal acid lipase deficiency in all siblings of the same parents.
Journal of clinical lipidologyLysosomal acid lipase deficiency: A hidden disease among cohorts of familial hypercholesterolemia?
Journal of clinical lipidology"Mutation-negative" familial hypercholesterolemia-When negative is positive.
Journal of clinical lipidologyTargeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development.
Current chemical genomics and translational medicineChildhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases.
Journal of clinical lipidologyPrenatal sonographic findings in a case of Wolman's disease.
Journal of clinical ultrasound : JCUQuantitation of the rates of hepatic and intestinal cholesterol synthesis in lysosomal acid lipase-deficient mice before and during treatment with ezetimibe.
Biochemical pharmacologyProgression of liver disease in children and adults with lysosomal acid lipase deficiency.
Current medical research and opinionCholesteryl Ester Storage Disease: An underdiagnosed cause of cirrhosis in adults.
Annals of diagnostic pathologyUpdate on lysosomal acid lipase deficiency: Diagnosis, treatment and patient management.
Medicina clinicaCholesteryl Ester Crystals in Lysosomal Acid Lipase Deficiency.
The New England journal of medicineLysosomal Acid Lipase Deficiency in 23 Spanish Patients: High Frequency of the Novel c.966+2T>G Mutation in Wolman Disease.
JIMD reportsManaging Cardiovascular Risk in Lysosomal Acid Lipase Deficiency.
American journal of cardiovascular drugs : drugs, devices, and other interventionsMorphology of Wolman cholesteryl ester storage disease.
BloodSurvival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study.
Orphanet journal of rare diseasesDiagnostic and therapeutic management of children with lysosomal acid lipase deficiency (LAL-D). Review of the literature and own experience.
Developmental period medicineSebelipase Alfa: A Review in Lysosomal Acid Lipase Deficiency.
American journal of cardiovascular drugs : drugs, devices, and other interventionsLysosomal acid lipase deficiency: Expanding differential diagnosis.
Molecular genetics and metabolismNovel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa.
The application of clinical geneticsOptions to consider when treating lysosomal acid lipase deficiency.
Journal of clinical lipidologySebelipase alfa (Kanuma) for lysosomal acid lipase deficiency.
The Medical letter on drugs and therapeuticsLysosomal Acid Lipase Deficiency Unmasked in Two Children With Nonalcoholic Fatty Liver Disease.
PediatricsSequencing for LIPA mutations in patients with a clinical diagnosis of familial hypercholesterolemia.
AtherosclerosisSuccessful long-term outcome of liver transplantation in late-onset lysosomal acid lipase deficiency.
Pediatric transplantationSebelipase alfa: enzymatic replacement treatment for lysosomal acid lipase deficiency.
Drugs of today (Barcelona, Spain : 1998)The Key Clinical Manifestations of Lysosomal Acid Lipase Deficiency.
Journal of pediatric gastroenterology and nutritionDisorders in the initial steps of steroid hormone synthesis.
The Journal of steroid biochemistry and molecular biologyA rare constellation of imaging findings in Wolman disease.
Medical journal, Armed Forces IndiaDoes Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?
International journal of molecular sciencesDyslipidaemia: Lysosomal acid lipase deficiency-a cautious leap forward.
Nature reviews. EndocrinologySebelipase alfa: first global approval.
DrugsDyslipidaemia: Promising new therapy for lysosomal acid lipase deficiency.
Nature reviews. CardiologyLysosomal Acid Lipase Deficiency--A New Therapy for a Genetic Lipid Disease.
The New England journal of medicineA Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency.
The New England journal of medicineAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Real-World Study of Management and Outcomes of Patients with Lysosomal Acid Lipase Deficiency (LAL-D) in France.
- Bilateral Adrenal Calcifications as an Imaging Clue to Wolman Disease in Early Infancy: A Case Report.
- Best Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion.
- Overview of pediatric and adult lysosomal acid lipase deficiency: expert recommendations from a Gulf cooperation council working group.
- Childhood to adult transition in youth patients with lysosomal acid lipase deficiency: 43 recommendations from experts.
- Lysosomal Acid Lipase Deficiency.
- Hepatic Steatosis: A Presentation of Cholesteryl Ester Storage Disease.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:75233(Orphanet)
- OMIM OMIM:620151(OMIM)
- MONDO:0019148(MONDO)
- GARD:7899(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q6710283(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
