[Secretory lysosome disorders in the immune synapse and other tissues].
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Unidad de Oncohematología Pediátrica, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, España. renejimenezgarcia@gmail.com
I Jiménez
IJ
García
A Galera
AG
Miñarro
E Llinares
EL
Riestra
M Bermúdez
MB
Cortés
S Alfayate
SA
Miguélez
J L Fuster
JL
Soler
D000938:Antigen-Presenting Cells; D002609:Chediak-Higashi Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D007223:Infant; D008214:Lymphocytes; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D016464:Lysosomal Storage Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D016116:Piebaldism / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D000081207:Primary Immunodeficiency Diseases