Secretory lysosome disorders in the immune synapse and other tissues

• Published in: Anales de pediatría (Barcelona, Spain : 2003) Vol. 76; no. 2; pp. 92 - 97
• Main Authors: García, I Jiménez, Miñarro, A Galera, Riestra, E Llinares, Cortés, M Bermúdez, Miguélez, S Alfayate, Soler, J L Fuster
• Format: Journal Article
• Language: Spanish
• Published: Spain 01.02.2012
• Subjects: Antigen-Presenting Cells; Chediak-Higashi Syndrome - diagnosis; Chediak-Higashi Syndrome - genetics; Chediak-Higashi Syndrome - immunology; Child; Child, Preschool; Humans; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Infant; Lymphocytes; Lymphohistiocytosis, Hemophagocytic - diagnosis; Lymphohistiocytosis, Hemophagocytic - genetics; Lymphohistiocytosis, Hemophagocytic - immunology; Lysosomal Storage Diseases - diagnosis; Lysosomal Storage Diseases - genetics; Lysosomal Storage Diseases - immunology; Piebaldism - diagnosis; Piebaldism - genetics; Piebaldism - immunology
• ISSN: 1695-9531
• DOI: 10.1016/j.anpedi.2011.09.003

Haemophagocytic syndrome (HS) is a common manifestation of several congenital disorders characterised by a disruption of lysosomal secretion, interrupting the cytolytic pathway and triggering a dysfunction in the immune synapse. In this situation, the recognition of certain extra-immunological manifestations may help in the diagnostic process. We describe the clinical and biological features present in two brothers with familial haemophagocytic lymphohistiocytosis type 3 (FHL-3), two patients with Griscelli syndrome type 2 (GS-2) and one patient with Chédiak-Higashi syndrome (CHS). Mutational assays at UNC13D were carried out on two brothers after diagnosing an early onset HS in the first one, yielding a positive result in both cases with a consequent diagnosis of FHL-3. The diagnosis of GS-2 was supported by positive results of mutational Rab27A studies in one patient with HS and abnormal pigmentation, and in her cousin who was affected by a similar abnormal pigmentation. The diagnosis of CHS was established in one patient with HS, abnormal pigmentation and atypical granules on cytological examination of a bone marrow smear. Diagnosis was confirmed in this patient by the finding of a homozygous LYST mutation. We point out the importance of recognising the presence of typical extra-immunological manifestations of certain congenital disorders of lysosome secretion in patients diagnosed with HS. The association of albinism and immunodeficiency has played a critical role in the recent identification of the molecular mechanism involved in these disorders.