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Reticular dysgenesis

MedGen UID:: 124417
•Concept ID:: C0272167
•: Disease or Syndrome

Synonyms:	ALEUKOCYTOSIS; Congenital aleukia; DeVaal disease; HEMATOPOIETIC HYPOPLASIA, GENERALIZED; RETICULAR DYSGENESIA; Severe combined immunodeficiency with leukopenia
SNOMED CT:	Reticular dysgenesis (111584000); De Vaal disease (111584000); Immunoerythromyeloid hypoplasia (111584000); Congenital aleukia (111584000); Reticular dysgenesia (111584000); Generalized hematopoietic hypoplasia (111584000); SCID - Severe combined immunodeficiency, neutropenia and thrombocytopenia (111584000); Severe combined immunodeficiency, neutropenia and thrombocytopenia (111584000)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	AK2 (1p35.1)

Monarch Initiative:	MONDO:0009973
OMIM®:	267500
Orphanet:	ORPHA33355

Definition

Reticular dysgenesis, the most severe form of inborn severe combined immunodeficiency (SCID), is characterized by absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immune functions, leading to fatal septicemia within days after birth (summary by Pannicke et al., 2009). [from OMIM]

Clinical features

From HPO

Lymphoproliferative disorder

MedGen UID:: 6162
•Concept ID:: C0024314
•: Neoplastic Process

A disorder characterized by proliferation of lymphocytes at various stages of differentiation. Lymphoproliferative disorders can be neoplastic (clonal, as in lymphomas and leukemias) or reactive (polyclonal, as in infectious mononucleosis).

See: Feature record | Search on this feature

Erythroid hypoplasia

MedGen UID:: 488912
•Concept ID:: C0542035
•: Disease or Syndrome

Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.

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Leukopenia

MedGen UID:: 6073
•Concept ID:: C0023530
•: Disease or Syndrome

An abnormal decreased number of leukocytes in the blood.

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Lymphopenia

MedGen UID:: 7418
•Concept ID:: C0024312
•: Disease or Syndrome

A reduced number of lymphocytes in the blood.

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Sepsis

MedGen UID:: 48626
•Concept ID:: C0036690
•: Disease or Syndrome

Systemic inflammatory response to infection.

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Hypoplasia of the thymus

MedGen UID:: 146347
•Concept ID:: C0685891
•: Congenital Abnormality

Underdevelopment of the thymus.

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Lack of T cell function

MedGen UID:: 336597
•Concept ID:: C1849426
•: Finding

Complete inability of T cells to perform their functions in cell-mediated immunity.

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Impaired T cell function

MedGen UID:: 395415
•Concept ID:: C1860127
•: Cell or Molecular Dysfunction

Abnormally reduced ability of T cells to perform their functions in cell-mediated immunity.

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Combined immunodeficiency

MedGen UID:: 751396
•Concept ID:: C2711630
•: Disease or Syndrome

A group of phenotypically heterogeneous genetic disorders characterized by profound deficiencies of T- and B-cell function, which predispose the patients to both infectious and noninfectious complications.

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Congenital agranulocytosis

MedGen UID:: 1631650
•Concept ID:: C4551555
•: Congenital Abnormality

Congenital onset of a marked decrease in the number of granulocytes.

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Decreased circulating IgG concentration

MedGen UID:: 1720114
•Concept ID:: C5234937
•: Finding

An abnormally decreased level of immunoglobulin G (IgG) in blood.

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Absent leukocyte alkaline phosphatase

MedGen UID:: 870282
•Concept ID:: C4024724
•: Finding

Alkaline phosphatase levels measured within leukocytes is below detectable levels.

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Abnormality of blood and blood-forming tissues
- Erythroid hypoplasia
Abnormality of metabolism/homeostasis
- Absent leukocyte alkaline phosphatase
Abnormality of the immune system
Neoplasm
- Lymphoproliferative disorder

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVReticular dysgenesis

Pathological Conditions, Signs and Symptoms
- Pathological process
  - Disease
    - Hereditary disease
      - Combined immunodeficiency
        Reticular dysgenesis

Follow this link to review classifications for Reticular dysgenesis in Orphanet.

Professional guidelines

PubMed

TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan.

Wakamatsu M, Kojima D, Muramatsu H, Okuno Y, Kataoka S, Nakamura F, Sakai Y, Tsuge I, Ito T, Ueda K, Saito A, Morihana E, Ito Y, Ohashi N, Tanaka M, Tanaka T, Kojima S, Nakajima Y, Ito T, Takahashi Y
J Clin Immunol 2022 Nov;42(8):1696-1707. Epub 2022 Jul 28 doi: 10.1007/s10875-022-01335-0. PMID: 35902420

Recent advances in understanding the pathogenesis and management of reticular dysgenesis.

Hoenig M, Pannicke U, Gaspar HB, Schwarz K
Br J Haematol 2018 Mar;180(5):644-653. Epub 2017 Dec 21 doi: 10.1111/bjh.15045. PMID: 29270983

Recent advances in the pathogenesis and treatment of nonimmune neutropenias in the neonate.

Calhoun DA, Christensen RD
Curr Opin Hematol 1998 Jan;5(1):37-41. doi: 10.1097/00062752-199801000-00007. PMID: 9515201

See all (4)

Recent clinical studies

Etiology

Frequency of pathogenic/likely pathogenic germline variants in cancer-related genes among children with acute leukemia in Saudi Arabia.

Alsultan A, Essa M, Aljefri A, Ayas M, Alharbi M, Alkhayat N, Al-Anzi F, Yassin F, Alkasim F, Alharbi Q, Abdullah S, Jastaniah W
Pediatr Blood Cancer 2020 Jul;67(7):e28340. Epub 2020 May 2 doi: 10.1002/pbc.28340. PMID: 32359129

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study.

Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Pulsipher MA, Parikh S, Martinez C, Kapoor N, O'Reilly R, Boyer M, Pai SY, Goldman F, Burroughs L, Chandra S, Kletzel M, Thakar M, Connelly J, Cuvelier G, Davila Saldana BJ, Shereck E, Knutsen A, Sullivan KE, DeSantes K, Gillio A, Haddad E, Petrovic A, Quigg T, Smith AR, Stenger E, Yin Z, Shearer WT, Fleisher T, Buckley RH, Dvorak CC
Blood 2017 Dec 21;130(25):2718-2727. Epub 2017 Oct 11 doi: 10.1182/blood-2017-05-781849. PMID: 29021228 Free PMC Article

Neutropenia associated with primary immunodeficiency syndromes.

Cham B, Bonilla MA, Winkelstein J
Semin Hematol 2002 Apr;39(2):107-12. doi: 10.1053/shem.2002.31916. PMID: 11957193

Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience.

Knutsen AP, Wall DA
J Clin Immunol 2000 Nov;20(6):466-76. doi: 10.1023/a:1026463900925. PMID: 11202237

Successful bone-marrow transplantation for reticular dysgenesis.

Levinsky RJ, Tiedeman K
Lancet 1983 Mar 26;1(8326 Pt 1):671-2. doi: 10.1016/s0140-6736(83)91968-2. PMID: 6132037

See all (11)

Diagnosis

TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan.

Recent advances in understanding the pathogenesis and management of reticular dysgenesis.

Hoenig M, Pannicke U, Gaspar HB, Schwarz K
Br J Haematol 2018 Mar;180(5):644-653. Epub 2017 Dec 21 doi: 10.1111/bjh.15045. PMID: 29270983

Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency.

Lapidot R, Alawdah L, Köhler JR, Paulson V, Levy O
Pediatr Infect Dis J 2018 Apr;37(4):356-358. doi: 10.1097/INF.0000000000001789. PMID: 28938259

Reticular dysgenesis in a preterm infant: a case report.

Cosar H, Kahramaner Z, Erdemir A, Kanik A, Turkoglu E, Sutcuoglu S, Ozturk C, Atabay B, Arun Ozer E
Pediatr Hematol Oncol 2010 Nov;27(8):646-9. doi: 10.3109/08880018.2010.509424. PMID: 20863163

Recent advances in the pathogenesis and treatment of nonimmune neutropenias in the neonate.

Calhoun DA, Christensen RD
Curr Opin Hematol 1998 Jan;5(1):37-41. doi: 10.1097/00062752-199801000-00007. PMID: 9515201

See all (14)

Therapy

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study.

Visual awareness of objects and their colour.

Pilling M, Gellatly A
Atten Percept Psychophys 2011 Oct;73(7):2026-43. doi: 10.3758/s13414-011-0161-3. PMID: 21695593

Reticular dysgenesis in a preterm infant: a case report.

Cosar H, Kahramaner Z, Erdemir A, Kanik A, Turkoglu E, Sutcuoglu S, Ozturk C, Atabay B, Arun Ozer E
Pediatr Hematol Oncol 2010 Nov;27(8):646-9. doi: 10.3109/08880018.2010.509424. PMID: 20863163

Recent advances in the pathogenesis and treatment of nonimmune neutropenias in the neonate.

Calhoun DA, Christensen RD
Curr Opin Hematol 1998 Jan;5(1):37-41. doi: 10.1097/00062752-199801000-00007. PMID: 9515201

Severe combined immunodeficiency (SCID) associated neutropenia: a lesson from monozygotic twins.

Niehues T, Schwarz K, Schneider M, Schroten H, Schröder E, Stephan V, Wahn V
Arch Dis Child 1996 Apr;74(4):340-2. doi: 10.1136/adc.74.4.340. PMID: 8669937 Free PMC Article

See all (14)

Prognosis

UK-5099, a mitochondrial pyruvate carrier inhibitor, recovers impaired neutrophil maturation caused by AK2 deficiency in human pluripotent stem cell models.

Wang J, Saiki N, Tanimura A, Noma T, Niwa A, Nakahata T, Saito MK
Biochem Biophys Res Commun 2023 Dec 20;687:149211. Epub 2023 Nov 3 doi: 10.1016/j.bbrc.2023.149211. PMID: 37949028

Reticular dysgenesis caused by an intronic pathogenic variant in AK2.

Ichikawa S, Prockop S, Cunningham-Rundles C, Sifers T, Conner BR, Wu S, Karam R, Walsh MF, Fiala E
Cold Spring Harb Mol Case Stud 2020 Jun;6(3) Epub 2020 Jun 12 doi: 10.1101/mcs.a005017. PMID: 32532877 Free PMC Article

Frequency of pathogenic/likely pathogenic germline variants in cancer-related genes among children with acute leukemia in Saudi Arabia.

Reticular dysgenesis in a preterm infant: a case report.

Cosar H, Kahramaner Z, Erdemir A, Kanik A, Turkoglu E, Sutcuoglu S, Ozturk C, Atabay B, Arun Ozer E
Pediatr Hematol Oncol 2010 Nov;27(8):646-9. doi: 10.3109/08880018.2010.509424. PMID: 20863163

Successful bone-marrow transplantation for reticular dysgenesis.

Levinsky RJ, Tiedeman K
Lancet 1983 Mar 26;1(8326 Pt 1):671-2. doi: 10.1016/s0140-6736(83)91968-2. PMID: 6132037

See all (12)

Clinical prediction guides

Reticular dysgenesis caused by an intronic pathogenic variant in AK2.

Reticular Dysgenesis and Mitochondriopathy Induced by Adenylate Kinase 2 Deficiency with Atypical Presentation.

Ghaloul-Gonzalez L, Mohsen AW, Karunanidhi A, Seminotti B, Chong H, Madan-Khetarpal S, Sebastian J, Vockley CW, Reyes-Múgica M, Vander Lugt MT, Vockley J
Sci Rep 2019 Oct 31;9(1):15739. doi: 10.1038/s41598-019-51922-2. PMID: 31673062 Free PMC Article

Visual awareness of objects and their colour.

Pilling M, Gellatly A
Atten Percept Psychophys 2011 Oct;73(7):2026-43. doi: 10.3758/s13414-011-0161-3. PMID: 21695593

Langerhans cell deficiency in reticular dysgenesis.

Emile JF, Geissmann F, Martin OC, Radford-Weiss I, Lepelletier Y, Heymer B, Espanol T, de Santes KB, Bertrand Y, Brousse N, Casanova JL, Fischer A
Blood 2000 Jul 1;96(1):58-62. PMID: 10891430

Lymphokine-activated killer cells in primary immunodeficiencies and acquired immunodeficiency syndrome.

Chin TW, Plaeger-Marshall S, Haas A, Ank BJ, Stiehm ER
Clin Immunol Immunopathol 1989 Dec;53(3):449-59. doi: 10.1016/0090-1229(89)90007-x. PMID: 2509119

See all (10)

MedGen

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Send to:

Links from Gene

Reticular dysgenesis

Definition

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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