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Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID; see this term) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated.
ORPHA:33355Classification level: Disorder
- AK2 deficiency
- Congenital aleukocytosis
- De Vaal disease
- Generalized hematopoietic hypoplasia
- SCID with leukopenia
- Severe combined immunodeficiency with leukopenia
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: D81.0
- OMIM: 267500
- UMLS: C0272167 C1282908
- MeSH: C538361
- GARD: 8625
- MedDRA: -
Reticular dysgenesis accounts for less than 2% of all SCID cases. The annual incidence has been estimated at 1/3,000,000-1/5,000,000. Both males and females are affected, and consanguinity has been noted in several families.
The disease presents earlier than other forms of SCID, at birth or early in the neonatal period, with signs of sepsis, failure to thrive, diarrhea, fever, recurrent infections including upper respiratory tract infections, oral candidiasis, perianal infections and abscesses, and bilateral sensorineural deafness. Despite recurrent infections, no significant lymphoid or tonsillar tissue is evident. Hemoglobin levels are usually within reference ranges at birth, but patients may develop anemia secondary to sepsis and chronic illness.
Reticular dysgenesis is characterized by profound neutropenia and T and natural killer (NK) cell lymphocytopenia, and is caused by mutations in the AK2 gene (1p34). The resulting deficiency in adenylate kinase 2 causes increased apoptosis of myeloid and lymphoid precursors. However, patients without this mutation have been observed implying an alternative cause. An imbalance of growth factor independent-1 transcription repressor (Gfi-1) and/or Gfi-1b has been proposed.
Diagnosis is based on evidence of sensorineural deafness in combination with evidence of a marked reduction of T and NK cell counts when compared to age-matched healthy controls. Materno-fetal engraftment is usually present.
Differential diagnosis includes all other forms of SCID.
Prenatal diagnosis can be performed in families where there is a family history and where the genetic mutation has been identified.
Transmission is autosomal recessive.
Management and treatment
The only curative treatment for this disease is allogenic hematopoietic stem cell transplantation.
Without treatment, patients die from septicemia within days after birth.
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