Ribosomopathy

Ribosomopathy is a class of diseases caused by defects in ribosome biogenesis or ribosome function. These disorders arise from mutations in genes encoding ribosomal proteins (RPs) or ribosome assembly and processing factors, leading to reduced ribosome production or impaired translational capacity. Although ribosomes are present in all cells, ribosomopathies frequently show tissue-specific phenotypes, particularly affecting the bone marrow, craniofacial development, and growth.

Diamond-Blackfan anemia (DBA) is among the most studied ribosomopathies. It is typically caused by haploinsufficiency of ribosomal protein genes such as RPS19 and other RP genes, presenting with anemia due to red cell aplasia and often congenital anomalies.

Shwachman-Diamond syndrome (SDS) results from mutations in SBDS and related genes that disrupt ribosome maturation, with pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities.

Treacher Collins syndrome, a craniofacial disorder, is linked to defects in ribosome biogenesis caused by TCOF1 mutations, reflecting the consequence of impaired neural crest development from ribosomal stress.

Dyskeratosis congenita (DC) arises from defects in telomerase components or dyskerin, affecting rRNA processing and ribosome biogenesis; DC features include mucocutaneous signs and bone marrow failure.

Other conditions, such as subsets of myelodysplastic syndromes with haploinsufficient ribosomal protein genes, illustrate the broader impact of ribosome defects on hematopoiesis.

Pathophysiology involves reduced ribosome numbers or altered ribosome function, leading to changes in the translation of specific mRNAs and selective vulnerability of certain tissues. Diagnosis relies on clinical assessment and genetic testing, whereas management is supportive and may include hematopoietic stem cell transplantation in severe cases. Ongoing research aims to understand tissue specificity and develop targeted therapies.