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Diseases linked to RIPK1 mutations

Maladie cosmopolite


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.


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.


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.


-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.

-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).


-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.


The disease is diagnosed by taking a blood sample for genetic analysis to check whether the RIPK1 gene is mutated.


-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 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.

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