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Disease Profile

Reticular dysgenesis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

D81.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

RD; Severe combined immunodeficiency with leukopenia; Congenital aleukia;

Categories

Congenital and Genetic Diseases; Immune System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 33355

Definition
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.

Epidemiology
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.

Clinical description
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.

Etiology
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.

Diagnostic methods
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
Differential diagnosis includes all other forms of 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
The only curative treatment for this disease is allogenic hematopoietic stem cell transplantation.

Prognosis
Without treatment, patients die from septicemia within days after birth.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of mitochondrial metabolism
0003287
Abnormality of neutrophils
0001874
Anemia
Low number of red blood cells or hemoglobin
0001903
Aplasia/Hypoplasia of the thymus
Absent/small thymus
Absent/underdeveloped thymus

[ more ]

0010515
Cellular immunodeficiency
0005374
Chronic otitis media
Chronic infections of the middle ear
0000389
Decreased circulating antibody level
0004313
Diarrhea
Watery stool
0002014
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Leukopenia
Decreased blood leukocyte number
Low white blood cell count

[ more ]

0001882
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Sepsis
Infection in blood stream
0100806
Severe combined immunodeficiency
0004430
30%-79% of people have these symptoms
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fever
0001945
Malabsorption
Intestinal malabsorption
0002024
Weight loss
0001824
5%-29% of people have these symptoms
Dehydration
0001944
Skin rash
0000988
Skin ulcer
Open skin sore
0200042
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Combined immunodeficiency
0005387
Congenital agranulocytosis
0005541
Hypoplasia of the thymus
Small thymus
0000778
Impaired T cell function
T-cell dysfunction
0005435
Lack of T cell function
0005354
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Reticular dysgenesis. Click on the link to view a sample search on this topic.