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Reticular dysgenesis in short
- Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID), marked by bilateral sensorineural hearing loss and a profound deficiency in both innate and adaptive immune responses.
- Without treatment, it typically results in life-threatening septicemia within the first few days of life.
Synonyms
- AK2 deficiency
- De Vaal disease
- SCID with sensorineural deafness
- Severe combined immunodeficiency with sensorineural deafness
- SCID with sensorineural hearing loss
- Severe combined immunodeficiency with sensorineural hearing loss
Prevalence: <1 / 1 000 000
Inheritance: Autosomal recessive
Age of onset: Infancy, Neonatal
Epidemiology – How common is Reticular dysgenesis?
- Reticular dysgenesis represents less than 2% of all severe combined immunodeficiency (SCID) cases.
- Its estimated annual incidence ranges from 1 in 3,000,000 to 1 in 5,000,000.
- The condition affects both males and females, and consanguineous parentage has been reported in several families.
What are the symptoms of Reticular dysgenesis?
Very frequent symptoms
- Abnormality of mitochondrial metabolism
- Abnormality of neutrophils
- Anemia
- Aplasia/Hypoplasia of the thymus
- Cellular immunodeficiency
- Chronic otitis media
- Decreased circulating antibody level
- Diarrhea
- Hearing impairment
- Leukopenia
- Recurrent respiratory infections
- Sepsis
- Severe combined immunodeficiency
Frequent symptoms
- Failure to thrive
- Fever
- Malabsorption
- Weight loss
Occasional symptoms
- Dehydration
- Skin rash
- Skin ulcer
Clinical description
- This form of SCID presents earlier than other types, typically at birth or during the early neonatal period.
- Clinical features include signs of sepsis, failure to thrive, diarrhea, fever, and recurrent infections such as upper respiratory tract infections, oral candidiasis, perianal infections, and abscesses, along with bilateral sensorineural hearing loss.
- Despite frequent infections, patients typically lack visible lymphoid or tonsillar tissue.
- Hemoglobin levels are usually normal at birth but may decline due to sepsis and chronic illness-related anemia.
What causes this condition?
- Reticular dysgenesis is defined by severe neutropenia along with marked T-cell and natural killer (NK) cell lymphocytopenia.
- It is most commonly caused by mutations in the AK2 gene located at 1p34, leading to a deficiency in adenylate kinase 2 and resulting in increased apoptosis of myeloid and lymphoid precursor cells.
- However, some patients without AK2 mutations have been identified, suggesting alternative pathogenic mechanisms.
- One proposed explanation involves an imbalance in the transcription repressors Gfi-1 and/or Gfi-1b.
Differential diagnosis
- Differential diagnosis includes all other forms of severe combined immunodeficiency (SCID).
Antenatal diagnosis
- Prenatal diagnosis can be performed in families where there is a family history and where the genetic mutation has been identified.
Genetic counseling
- Transmission is autosomal recessive.
Management and treatment – How is this condition treated?
- The only curative treatment for this disease is allogenic hematopoietic stem cell transplantation.
Prognosis
- Without treatment, patients die from septicemia within days after birth.
