Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Children and Adult Hemophagocytic Syndrome (HLHa)

Summary: Different study of HLHa patients :
  -  Diagnosis criteria, because criteria are based on pediatric genetic studies.
  -  Physiopathological studies: genetic studies have demonstrated the role of CD8+ cells, in particular because they have a genetic defect affecting their cytotoxic functions in HLH pediatric. the aim is to establish if the same defect is found in both some or in all of HLHa patients. If this is the case, to then establish whether hypomorphic genetic mutations are responsible.

Detailed description: Formation of a prospective and retrospective infant, adolescent and adult HLH patients cohort.
  Collection of clinical and biological, therapeutics, informations, in a register, The collection of information is:
  -  To identify clinical and biological criteria specific to HLHa
  -  Classify patients into homogeneous groups, based on clinical biological scalability in particular, with regards to their response to treatment
  -  Identify and analyze the behavioral therapy Creation of a bank of biological samples for use in the study of the pathophysiology of HLHa.
  Background:
  The hemophagocytic syndrome in infant, adolescent and adults (HLH) is a serious and often lethal condition. The study of literature series HLHa shows that these syndromes frequently develop in immunocompromised patients (renal transplant, HIV, collagen in Processing immunosuppressants) in the course of a viral infection. HLH syndrome has also been described as a clinical form of lymphoma or connective disease (lupus). These clinical forms are rare, severe and recurrent suggesting the possibility that immune deficiency could be involved. The study of pediatric forms has definitely established a link between HLH syndrome and the presence of immune deficiency by identifying the nature of the latter. Four genetically determined diseases are manifested by HLH syndrome. These conditions are Family lymphohistiocytosis (LHF) syndrome, Chediak-Higashi CHS syndrome, Griscelli (GS) type 2 syndromes and X-linked lymphoproliferative (XLP 1 and 2). The mutated genes are respectively perforin Unc 13.4 and syntaxin in the LHF2, 3, 4 (10q locus genetic for LHF 1), CHS1/LYST (Lysosomal Trafficking regulator) in the CHS, in the Rab27a GS type 2, and XIAP and SH2D1A in the XLP. It is now well established that proteins encoded by these genes are necessary for the cytotoxic function of CD8 + and in the absence of these proteins is the cytotoxocity CD8 + deficient. Also, closed clinical and biological characteristics shared by pediatric genetic and adult forms suggest the existence of immune defects responsible for some or all HLH adult patients.

Eligibility: Inclusion Criteria:
  Major criteria:
  -  hemophagocytosis found in a specimen histology.
  -  Fever
  -  Splenomegaly
  Minor criteria:
  -  adenopathy
  -  cytopenia> 2 cell lines Hemoglobin <9 g / dl (less than 4 weeks and> 12 g / dl) Platelets <100 000 x 10 / l Neutrophils <1 10 / l
  -  hypertriglyceridaemia and / or hypofibrinogenaemia Elevated triglycerides> 3 mmol / l Fibrinogen <1.5 g / l
  -  Ferritin> 500 microg / L
  These criteria will be those used for the diagnosis of HLH in adults:
  One major criterion and two minor (including hyper ferritin or hypertriglyceridemia) 3 minor criteria (including hyper ferritin or hypertriglyceridemia)
  Exclusion Criteria:
  -  Pregnant women
  -  A person under guardianship
  -  Patients under the age of 2 years

Relevance to patient case: not relevant