Reticular dysgenesis

A rare genetic disorder affecting the immune system

Reticular dysgenesis
Autosomal recessive - en.svg
Reticular dysgenesis is inherited in an autosomal recessive manner
Synonyms	AK2 deficiency, Congenital aleukocytosis, De Vaal disease, Generalized hematopoietic hypoplasia, SCID with leukopenia
Specialty	Immunology, Hematology, Medical genetics
Symptoms	Severe combined immunodeficiency, profound neutropenia, sensorineural deafness, failure to thrive
Complications	Life-threatening infections, sepsis, hearing loss
Usual onset	At birth or within the first few weeks of life
Duration	Lifelong without treatment
Types	A form of Severe combined immunodeficiency (SCID)
Causes	Mutations in the AK2 gene affecting mitochondrial energy metabolism in hematopoietic stem cells
Risk factors	Autosomal recessive inheritance; consanguinity
Diagnosis	Newborn screening, flow cytometry, genetic testing, bone marrow biopsy
Differential diagnosis	Other forms of SCID, congenital neutropenia, hematopoietic disorders
Prevention	Genetic counseling for at-risk families
Treatment	Hematopoietic stem cell transplantation (HSCT)
Medication	Prophylactic antibiotics, antifungals, and antiviral agents; immunoglobulin therapy
Prognosis	Poor without treatment; significantly improved outcomes with early HSCT
Frequency	Very rare
Deaths	High mortality rate without early diagnosis and transplantation

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