Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation

Taurisano, Roberta; Maiorana, Arianna; Benedetti, Fabrizio; Dionisi‐Vici, Carlo; Boldrini, Renata; Deodato, Federica

doi:10.1007/s00431-014-2338-y

Cited by 47 publications

(51 citation statements)

References 10 publications

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“…Patient 2 presented with severe anemia (hemoglobin 6.8 g/dL) and thrombocytopenia (platelet count 50 K/uL). She was diagnosed with secondary hemophagocytic lymphohistiocytosis, which has been previously noted in infantile LAL-D patients [15]. Her anemia was determined to be secondary to both the hematologic-related complications of infantile LAL-D, as well as iron deficiency.…”

Section: Clinical Manifestations Outside the Therapeutic Scope Of Ertmentioning

confidence: 71%

Early diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy

Cohen¹,

Burfield²,

Valdez-Gonzalez³

et al. 2019

Orphanet J Rare Dis

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Background Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form also known as Wolman disease. We sought to determine the outcomes and clinical needs of infants diagnosed with LAL-D, treated with enzyme replacement therapy (ERT). Methods A chart review was conducted on two infantile-onset LAL-D patients to determine clinical outcomes based on laboratory results, abdominal imaging, growth and dietary records, cardiology, endocrinology, ophthalmology, hematology, and neurocognitive evaluations. Results Two patients, both diagnosed and treated before 6 months old, demonstrated clinical improvement following weekly ERT. They required dosage increases to optimize growth and symptomatology. Both received a formula low in long chain triglycerides and high in medium chain triglycerides, an intervention that allowed significant catch-up growth. Patient 1 required treatment for partial adrenal insufficiency and hypothyroidism. Both patients demonstrated reduction in liver and spleen size and varying degrees of improved liver function. Neither experienced serious adverse reactions to ERT. Conclusion ERT has led to longer and healthier survival of affected infants. It is imperative that dietary interventions and systemic clinical care become integral to the management. Continued evidence of survival and clinical improvement in this population, coupled with available mass spectrometry enzyme assay from dried blood spots, raises the question of this rare and possibly underdiagnosed disorder’s candidacy for newborn screening. Electronic supplementary material The online version of this article (10.1186/s13023-019-1129-y) contains supplementary material, which is available to authorized users.

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Section: Clinical Manifestations Outside the Therapeutic Scope Of Ertmentioning

confidence: 71%

Early diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy

Cohen¹,

Burfield²,

Valdez-Gonzalez³

et al. 2019

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Despite the reports of occurrence of anemia, thrombocytosis, and the accumulation of lipids also in the bone marrow and the lymph nodes, few data are available on the impact of LAL-D on immune response in humans. Very recently, the presence of secondary hemophagocytic lymphohistiocytosis (HLH) was described in WD case reports [57][58][59][60][61][62][63]…”

Section: Genetics Of Lal Deficiencymentioning

confidence: 99%

Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target

Gomaraschi

Bonacina

Norata

2019

Trends in Pharmacological Sciences

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Lysosomal acid lipase (LAL) hydrolyzes cholesterol esters and triglycerides to free cholesterol and fatty acids,that are then used for the metabolic purposes in the cell. The process also occurs in immune cells which adapt their metabolic machinery to cope with the different energetic requirements associated to cell activation, proliferation and/or polarization. Deficiency of LAL not only causes severe lipid accumulation, but also impacts the immunometabolic signature in animal models. In humans, LAL deficiency has been recently associated with a peculiar clinical immune phenotype, secondary hemophagocytic lymphohistiocytosis. These observations indicate that LAL represents a critical player for cellular immunometabolic modulation and the availability of an effective enzyme replacement strategy makes LAL an attractive target to rewire the immunometabolic machinery of immune cells beyond its role in controlling cellular lipid metabolism.

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“…1), confirming FHL-3. The second patient with "full" HLH had the homozygous mutation c.553delT resulting in a frame shift in the gene encoding lysosomal acid lipase (LIPA) and was diagnosed with Wolman disease, which is known to sometimes present with an HLH phenotype [23]. 1°HLH was also diagnosed in two patients with "incomplete/atypical" HLH.…”

Section: Figmentioning

confidence: 99%

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis

et al. 2017

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We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years.

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Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation

Abstract: This case indicates that WD can cause secondary HLH and suggests that a careful metabolic workup should be performed when facing to a pediatric patient with HLH.

Cited by 47 publications

References 10 publications

Early diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy

Early diagnosis of infantile-onset lysosomal acid lipase deficiency in the advent of available enzyme replacement therapy

Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis

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