Journal article
Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features
Biomolecules (Basel, Switzerland), Vol.11(3), p.367
02/28/2021
DOI: 10.3390/biom11030367
PMCID: PMC7997317
PMID: 33670882
Abstract
Majeed syndrome is a multi-system inflammatory disorder affecting humans that presents with chronic multifocal osteomyelitis, congenital dyserythropoietic anemia, with or without a neutrophilic dermatosis. The disease is an autosomal recessive disorder caused by mutations in
, the gene encoding the phosphatidic acid phosphatase LIPIN2. It is exceedingly rare. There are only 24 individuals from 10 families with genetically confirmed Majeed syndrome reported in the literature. The early descriptions of Majeed syndrome reported severely affected children with recurrent fevers, severe multifocal osteomyelitis, failure to thrive, and marked elevations of blood inflammatory markers. As more affected families have been identified, it has become clear that there is significant phenotypic variability. Data supports that disruption of the phosphatidic acid phosphatase activity in LIPIN2 results in immune dysregulation due to aberrant activation of the NLRP3 inflammasome and overproduction of proinflammatory cytokines including IL-1β, however, these findings did not explain the bone phenotype. Recent studies demonstrate that
deficiency drives pro-inflammatory M2-macrophages and enhances osteoclastogenesis which suggest a critical role of lipin-2 in controlling homeostasis at the growth plate in an inflammasome-independent manner. While there are no approved medications for Majeed syndrome, pharmacologic blockade of the interleukin-1 pathway has been associated with rapid clinical improvement.
Details
- Title: Subtitle
- Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features
- Creators
- Polly J Ferguson - Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USAHatem El-Shanti - Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Biomolecules (Basel, Switzerland), Vol.11(3), p.367
- DOI
- 10.3390/biom11030367
- PMID
- 33670882
- PMCID
- PMC7997317
- NLM abbreviation
- Biomolecules
- ISSN
- 2218-273X
- eISSN
- 2218-273X
- Publisher
- Switzerland
- Grant note
- R01AR05970 / NIH HHS
- Language
- English
- Date published
- 02/28/2021
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984070682402771
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