Majeed syndrome is a rare genetic disorder. Patients with this syndrome suffer from Chronic Recurrent Multifocal Osteomyelitis (CRMO), Congenital Dyserythropoietic Anaemia (CDA) and inflammatory dermatosis.
The Majeed Syndrome is characterised by recurrent, long-lasting episodes of bone inflammation in several locations (chronic recurrent multifocal osteomyelitis, or CRMO). In addition, patients have innate anaemia (congenital dyserythropoietic anaemia) and inflammation of the skin (inflammatory dermatosis). The CRMO associated with this syndrome can be differentiated from isolated CRMO. With Majeed, it starts at a younger age (in the first years of life), the episodes with bone inflammation occur more frequently, and the periods when the patient is symptom-free are shorter. It is believed to be a life-long condition. It can lead to retarded growth and/or joint contractures. The anaemia is characterised by microcytosis (unusually small red blood cells) in the blood and bone marrow. The severity of the anaemia can vary from mild, unnoticeable to a form requiring blood transfusion. The skin inflammation (inflammatory dermatosis) is often Sweet syndrome, but may also be a skin condition with pustules (pustulosis).
The disease is caused by mutations in the LPIN2 gene on chromosome 18p (error in the DNA) that codes for a protein called lipin-2. Researchers believe that this protein plays a role in the processing of fats (lipid metabolism). However, no lipid abnormalities have been found in patients with Majeed syndrome. Lipin-2 may also be involved in controlling inflammation and play a role in cell division.
Mutations in the LPIN2 gene alter the structure and function of lipin-2. It is unclear how these genetic changes lead to bone disease, anaemia, and inflammation of the skin in people with Majeed syndrome.
It is inherited as an autosomal recessive disease. This type of transmission means that to get the Majeed syndrome, a person must have inherited two mutated genes, one from the mother and the other from the father. Hence, both parents are usually carriers of the gene, but not patients (a carrier has only one mutated copy but not the disease). Although carriers typically do not show symptoms of the condition, some parents of children with Majeed syndrome have an inflammatory skin disorder called psoriasis. Parents who have a child with Majeed syndrome have a 25% risk that a second child will have the disease as well. Prenatal diagnosis is possible.
How is the diagnosis made?
The disease can be suspected based on a patient’s symptoms. Blood tests, such as erythrocyte sedimentation rate (BSE), CRP, a complete blood count are important when the disease is active to determine the degree of inflammation. The final diagnosis can be confirmed by genetic analysis.
There is no standardised therapeutic treatment for Majeed syndrome. The bone inflammation (CRMO) is usually treated with non-steroidal anti-inflammatory drugs (NSAID’s). Physical therapy is important to avoid atrophy and contractures due to the reduced use of the joints and muscles. If CRMO does not respond to NSAIDs, corticosteroids can be used (briefly) to control CRMO and skin conditions. Anti-IL1 drugs are being studied. The first results are promising. Anaemia is treated with red blood cell transfusions if required.
The long-term prognosis depends on the severity of the symptoms, particularly the severity of the anaemia (dyserythropoietic anaemia) and disease complications. If left untreated, the quality of life is poor as a result of the recurrent pain, chronic anaemia and the possible complications, such as contractures and atrophy of the muscles as a result of not using them. It is not possible to cure the disease completely because it is a hereditary disease. If better medication is found, it may be possible to better control the disease in the future.