Secondary Hemophagocytic Lymphohistiocytosis in an Infant with Wolman Disease

Bartakke, Sandip; Nisal, Amit; Bafna, Vineet; Valecha, Aashna

doi:10.1007/s12288-020-01350-4

Cited by 3 publications

(4 citation statements)

References 2 publications

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“…67 Lysosomal acid lipase deficiency is frequently linked to HLH (Table 4). [68][69][70][71][72][73][74][75][76][77][78][79] They were all diagnosed with HLH within the first 6 months of life. The majority displayed symptoms of HLH, such as fever, and were later diagnosed with WD.…”

Section: Lysosomal Acid Lipase Deficiencymentioning

confidence: 99%

“…Because symptoms of HLH and WD were rapidly progressive and refractory to treatment, at least five patients were diagnosed with WD after death. 68,69,72,76 The only patient, who was diagnosed with LAL-D prior to the onset of HLH, displayed typical LAL-D findings, such as abdominal distention, hepatosplenomegaly, and bilateral adrenal calcification, but died before receiving ERT. 77 Some patients had temporarily improved HLH symptoms with immunochemotherapy treatment but died of multiple organ failure or chronic liver failure due to the progression of WD.…”

Section: Lysosomal Acid Lipase Deficiencymentioning

confidence: 99%

“…None of them was linked to EBV infection. Because symptoms of HLH and WD were rapidly progressive and refractory to treatment, at least five patients were diagnosed with WD after death 68,69,72,76 . The only patient, who was diagnosed with LAL‐D prior to the onset of HLH, displayed typical LAL‐D findings, such as abdominal distention, hepatosplenomegaly, and bilateral adrenal calcification, but died before receiving ERT 77 .…”

Section: Introductionmentioning

confidence: 99%

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Rare diseases presenting with hemophagocytic lymphohistiocytosis

Kanegane

Noguchi

Yamada

et al. 2023

Pediatrics International

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Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory disorder characterized by hypercytokinemia caused by excessive activation of cytotoxic T cells and macrophages. HLH is caused by a variety of factors and is classified into primary and secondary HLH. Familial HLH (FHL) types 1–5, X‐linked lymphoproliferative syndrome types 1 and 2, and FHL syndrome with hypopigmentation are all examples of primary HLH. Secondary HLH, on the other hand, is linked to infections, malignant tumors, autoimmune diseases, and other diseases. The causes of HLH vary, and finding the underlying disease is critical for diagnosis and treatment. The majority of HLH is caused by the aforementioned conditions; however, approximately 10% of cases are caused by rare diseases such as inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Novel IEI, such as RhoG, MAP kinase activating death domain, TIM3, and ZNFX1 deficiencies, have recently been identified as causes of HLH. IEM patients are rarely associated with HLH. Surprisingly, children with lysinuric protein intolerance and lysosomal acid lipase deficiency (Wolman disease) frequently develop HLH. This review focuses on the most recent knowledge of HLH caused by rare diseases such as IEI and IEM.

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Section: Lysosomal Acid Lipase Deficiencymentioning

confidence: 99%

Section: Lysosomal Acid Lipase Deficiencymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rare diseases presenting with hemophagocytic lymphohistiocytosis

Kanegane

Noguchi

Yamada

et al. 2023

Pediatrics International

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“…Clinical manifestations include failure to thrive, vomiting, diarrhoea, hepatosplenomegaly [7] and calcification of the adrenal glands [8]. Another common initial presentation is with a secondary hemophagocytic syndrome [9][10][11]. Without treatment, infants with WD do not survive beyond 6 months of age [12].…”

Section: Introductionmentioning

confidence: 99%

Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease

de Castro,

Jones,

de las Heras

et al. 2024

Orphanet J Rare Dis

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Background Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3–5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. Methods We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. Results Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. Conclusion 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the ‘trough’ periods before the next dosing, even with this intensive regimen.

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