INTRODUCTION: 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.
PATIENTS AND 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.