Definition
This is a group of rare auto-inflammatory diseases of recent description (2018). These diseases are caused by mutations in the RIPK1 (Receptor Interacting Protein serine/threonine Kinase 1) gene.
RIPK1 is a key protein in cell metabolism, involved in the regulation of inflammation, cell survival and cell death.
Epidemiology
Fewer than 50 cases have been reported worldwide.
This is a cosmopolitan disease, with slightly more cases in the Middle East and a slight predominance of women. The disease begins shortly after birth.
Genetic
These are genetic diseases. There are two forms of the disease, depending on the type and location of the mutation:
- a recessive form, requiring the presence of 2 mutations on the 2 chromosomes.
- a dominant form, with a single mutation on one of the 2 chromosomes.
Clinical
-The recessive form causes chronic, severe inflammation of the intestines from birth, as well as a deficiency in immunity leading to severe, recurrent infections. In addition, patients suffer from stunted growth, a large spleen and a large liver. This form is known as RIPK1-deficiency immunodeficiency and inflammation.
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-The dominant form causes recurrent episodes of fever, mouth ulcers and large lymph nodes, as well as a large liver and spleen. This form is called CRIA for Cleavage-Resistant RIPK1-Induced Autoinflammatory syndrome (named after the location of the abnormality on the RIPK1 gene).
Biology
-In the recessive form, there is a deficiency of certain white blood cells such as lymphocytes, as well as a possible reduction in immunoglobulins, which are antibodies designed to fight certain types of infection.
-In the dominant form, there is inflammation in the blood, with microcytic anemia.
Diagnostic
The disease is diagnosed by taking a blood sample for genetic analysis to check whether the RIPK1 gene is mutated.
Evolution
-The recessive form is severe, with a reported 50% mortality rate. Deaths are generally due to infections caused by the immune deficiency.
-There are no reported cases of death in the dominant form.
At present, there are no renal complications of the inflammatory amyloidosis type in this disease.
Disease flare-ups have a major impact on patients' quality of life.
Treatment
-Treatment of the recessive form relies on bone marrow transplantation.
-In the dominant form, treatment is based on an injectable drug targeting interleukin 6, a cytokine involved in the high inflammation associated with this disease.