Reticular dysgenesis

A rare genetic disorder affecting the immune system

Reticular dysgenesis is a rare and severe form of severe combined immunodeficiency (SCID), characterized by the absence of both lymphocytes and granulocytes, leading to a profound immunodeficiency. It is considered one of the most severe forms of SCID due to the lack of both adaptive and innate immune responses.

Pathophysiology

Reticular dysgenesis is caused by mutations in the AK2 gene, which is located on chromosome 1. The AK2 gene encodes the adenylate kinase 2 enzyme, which is crucial for energy metabolism in cells, particularly in the mitochondria. The deficiency of this enzyme affects the development of hematopoietic stem cells, leading to the failure of myeloid and lymphoid cell lineages.

Clinical Presentation

Patients with reticular dysgenesis typically present in the neonatal period with severe infections, failure to thrive, and neutropenia. The absence of neutrophils and lymphocytes results in an inability to mount an effective immune response, making affected individuals highly susceptible to bacterial, viral, and fungal infections.

Diagnosis

The diagnosis of reticular dysgenesis is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests reveal severe lymphopenia and neutropenia. Genetic testing can confirm mutations in the AK2 gene, which is diagnostic of the condition.

Treatment

The primary treatment for reticular dysgenesis is hematopoietic stem cell transplantation (HSCT), which can restore immune function. Prior to transplantation, patients may require supportive care, including antibiotics, antifungals, and immunoglobulin replacement therapy.

Prognosis

Without treatment, reticular dysgenesis is fatal in infancy due to overwhelming infections. However, with successful hematopoietic stem cell transplantation, long-term survival is possible, and immune function can be restored.

Related pages

• Severe combined immunodeficiency
• Hematopoietic stem cell transplantation
• Neutropenia
• Lymphopenia