Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance☆,☆☆
Section snippets
METHODS
Peripheral blood samples were obtained after parents gave informed consent. Bone marrow aspirations were required for unexplained cytopenia. Lymphocyte populations were counted by immunofluorescence with monoclonal antibodies on a flow cytometer (Facstar-plus, Becton Dickinson). Antigen-induced lymphocyte proliferation and NK cell activity against K562 were determined according to standard procedures. For cytokines, sIL2-R, and sCD8, plasma was tested by enzyme-linked immunosorbent assay.
RESULTS
Patients 1 and 2, who were misdiagnosed with FHL, are brothers who presented a similar clinical picture during the neonatal period.8 The first 48 hours of life were accompanied by life-threatening cyanosis, bradycardia, and hypotension. Rapidly progressive hepatosplenomegaly, cutaneous hemorrhagic syndrome, hypotonia, chewing movements, and tremor were also present. Anemia (patient 1: hemoglobin, 100 g/L; patient 2: 120 g/L), thrombocytopenia (patient 1: 62 × 109/L; patient 2: 135 × 109/L), and
DISCUSSION
The diagnostic criteria for HLH were defined by the FHL Study Group of the Histiocyte Society in 1991.1 They include fever, splenomegaly, hypofibrinogenemia, hypertriglyceridemia, and pancytopenia. Hemophagocytosis in bone marrow, spleen, or lymph nodes without evidence of malignancy is required for the diagnosis. In the 4 patients with LPI studied, the symptoms fulfilled all HLH diagnostic criteria, including bone marrow abnormalities. Fever was not a prominent finding, but diagnostic
Acknowledgements
We thank Maud Giraud for perfect organization, the nurses of the Centre d’Investigations Cliniques for taking care of the patients and their families, and Martine Raveau for her excellent technical assistance.
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Lysinuric protein intolerance mimicking N-acetylglutamate synthase deficiency in a nine-year-old boy
2021, Molecular Genetics and Metabolism ReportsCitation Excerpt :The decreased factor V level cannot be explained by hepatic dysfunction as the other coagulation factors were normal. The remaining hematological findings were similar to the patients reported in the literature [9,10,15,16,18–23]. Growth hormone deficiency is secondary to arginine depletion in LPI [2].
Hemophagocytic Lymphohistiocytosis: Lessons Learned from the Dark Side
2020, Immunology and Allergy Clinics of North AmericaCitation Excerpt :The high percentage of PIDD patients found in this cohort underscores the importance of whole-exome sequencing or large PIDD panel testing in patients with HLH without identifiable linkage to HLH causing disease. Several inborn errors of metabolism can also present with HLH, in particular, lysinuric protein intolerance.52 The exact mechanism is not well understood; however, the accumulation of nondegraded substrates in macrophages may potentially lead to inflammasome activation, thereby triggering uncontrolled activation of macrophages, and ultimately development of HLH.
Pediatric hemophagocytic lymphohistiocytosis
2020, BloodAmino Acid Metabolism
2020, Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Metabolic DisordersGenetic diseases predisposing to HLH
2020, Stiehm's Immune Deficiencies: Inborn Errors of Immunity
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