Secondary hemophagocytic lymphohistiocytosis in an infant with Wolman disease Hemophagocytosis and Wolman disease

Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target

“…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]…”

Lysosomal acid lipase deficiency in pediatric patients: a scoping review

“…At the end of the selection process, only 108 articles were retained. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , …”

Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis

“…Our case shows that WD, along with other treatable metabolic diseases, should be considered in the diagnostic workup of splenomegaly diagnosed at birth for an early diagnosis and treatment. HLH features could have been misleading in suspecting WD, that was not immediately considered due to the extreme rarity of the disease association (15 WD cases with HLH have been reported at today) ( Table 2 ), the relatively slight elevation of total cholesterol levels, the negative bone marrow aspirate, and the lack of visualization of the adrenal calcification at the abdominal US [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] . Most probably due to the diagnostic delay, our patient developed severe HLH features.…”

“… Geographic origin Parents consanguinity LIPA genotype LIPA variation(s) pathogenicity Treatments Outcome Present case Ghana No c.358A > C / c.428 + 1G > T Likely pathogenic/pathogenic Tocilizumab 8 mg/kg one infusion only Sebelipase alpha 1 mg/kg/wk. IV for one month then 2 mg/kg /week IV Died at 17 months Santos Silva et al [10] Poland Not reported c.509C > A(p.S103R)/ c.796G > T(p.G266X) Both pathogenic Sebelipase alpha 1 mg/kg IV (two weeks), 3 mg/kg IV (two weeks), and 5 mg/kg IV Died at 6 months Santos Silva et al [10] Portuguese (Roma ethnicity) Yes (first cousins) Homozygous c.966 + 2 T > G-intron 9 Likely pathogenic (splice site) Sebelipase alpha 1 mg/kg (one dose) Died at 5 months Küçükçongar Yavaş et al [8] Turkey Yes Homozygous c.260G > T(p.Gly87Val) Pathogenic Supportive treatments Died at 3 months Tinsa et al [3] Tunisia Yes Homozygous c.153C > A (p.Tyr51*) Likely pathogenic (premature stop codon) Supportive treatments Died at 4 months Alabbas et al [9] Saudi Arabia Yes (first degree) Homozygous c.(428 + 1_967–1)_(*1_? )del Deletion of exons 9 and 10, likely pathogenic Anakinra 10 mg/kg twice per day for 7 days Etoposide 150 mg/m2 (3 doses) Died at 5 months Al Essa M et al [4] Saudi Arabia Yes (first cousins) ND – Supportive treatments Died at 4 months Perry R et al [5] Canada ND ND – Chemotherapy NA Perry R et al [...…”

“…The majority of symptoms of WD are rather unspecific, whereas, besides hepatosplenomegaly, the hallmarks of the disease are: 1) triangular symmetrically enlarged and calcific adrenal glands; 2) high total serum concentrations of cholesterol, LDL, triglycerides, and low serum concentration of HDL; 3) lymphocytosis in peripheral smear and vacuolated macrophages in bone marrow [1] ; 4) elevated serum levels of the oxysterols cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) [2] . Hemophagocytic lymphohistiocytosis (HLH) associated with WD has so far been reported in 15 cases [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] .…”