MCID: NTR049
MIFTS: 36

Neutropenia, Severe Congenital, 3, Autosomal Recessive

Categories: Genetic diseases, Rare diseases, Blood diseases, Bone diseases, Immune diseases, Nephrological diseases

Aliases & Classifications for Neutropenia, Severe Congenital, 3, Autosomal Recessive

MalaCards integrated aliases for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

Name: Neutropenia, Severe Congenital, 3, Autosomal Recessive 57
Neutropenia, Severe Congenital 3, Autosomal Recessive 57 75 13
Kostmann Disease 57 53 75
Scn3 57 53 75
Severe Congenital Neutropenia 3, Autosomal Recessive 29 6
Agranulocytosis Infantile 53 75
Kostmann Syndrome 76 59
Neutropenia, Congenital, Severe, Type 3, Autosomal Recessive 40
Severe Congenital Neutropenia Autosomal Recessive 3 53
Severe Congenital Neutropenia Type 3 59
Severe Congenital Neutropenia 73
Agranulocytosis, Infantile 57
Infantile Agranulocytosis 59

Characteristics:

Orphanet epidemiological data:

59
kostmann syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
only some patients showed neurologic involvement


HPO:

32
neutropenia, severe congenital, 3, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 59  
Rare immunological diseases


Summaries for Neutropenia, Severe Congenital, 3, Autosomal Recessive

OMIM : 57 Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities (summary by Boztug et al., 2010). The Swedish physician Rolf Kostmann (1956) described an autosomal recessive hematologic disorder, termed infantile agranulocytosis, with severe neutropenia with an absolute neutrophil count below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disorder was later termed Kostmann syndrome (Skokowa et al., 2007). Lekstrom-Himes and Gallin (2000) discussed severe congenital neutropenia in a review of immunodeficiencies caused by defects in phagocytes. In addition to Kostmann agranulocytosis, recessively inherited neutropenic syndromes include congenital neutropenia with eosinophilia (257100), Chediak-Higashi syndrome (214500), and Fanconi pancytopenic syndrome (see 227650). For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). (610738)

MalaCards based summary : Neutropenia, Severe Congenital, 3, Autosomal Recessive, also known as neutropenia, severe congenital 3, autosomal recessive, is related to severe congenital neutropenia and neutropenia. An important gene associated with Neutropenia, Severe Congenital, 3, Autosomal Recessive is HAX1 (HCLS1 Associated Protein X-1). The drugs Busulfan and Fludarabine have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and neutrophil, and related phenotypes are seizures and global developmental delay

UniProtKB/Swiss-Prot : 75 Neutropenia, severe congenital 3, autosomal recessive: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures.

Wikipedia : 76 Kostmann syndrome is a group of diseases that affect myelopoiesis, causing a congenital form of... more...

Related Diseases for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Graphical network of the top 20 diseases related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:



Diseases related to Neutropenia, Severe Congenital, 3, Autosomal Recessive

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
psychomotor retardation (in some patients)
seizures (in some patients)

Neoplasia:
increased risk of myelodysplastic syndromes
increased risk of leukemia

Immunology:
neutropenia
recurrent bacterial infections


Clinical features from OMIM:

610738

Human phenotypes related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

32 (show all 6)
# Description HPO Frequency HPO Source Accession
1 seizures 32 occasional (7.5%) HP:0001250
2 global developmental delay 32 occasional (7.5%) HP:0001263
3 neutropenia 32 HP:0001875
4 leukemia 32 HP:0001909
5 recurrent bacterial infections 32 HP:0002718
6 myelodysplasia 32 HP:0002863

Drugs & Therapeutics for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Drugs for Neutropenia, Severe Congenital, 3, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 68)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1 55-98-1 2478
2
Fludarabine Approved Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1 21679-14-1, 75607-67-9 30751
3
Vidarabine Approved, Investigational Phase 2, Phase 3,Phase 3,Early Phase 1 24356-66-9 32326 21704
4
alemtuzumab Approved, Investigational Phase 2, Phase 3,Phase 1,Early Phase 1,Not Applicable 216503-57-0
5
Cyclophosphamide Approved, Investigational Phase 2, Phase 3,Phase 1,Not Applicable,Early Phase 1 50-18-0, 6055-19-2 2907
6
Lenograstim Approved, Investigational Phase 2, Phase 3 135968-09-1
7 Alkylating Agents Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
8 Anti-Infective Agents Phase 2, Phase 3,Phase 3,Early Phase 1
9 Antilymphocyte Serum Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable
10 Antimetabolites Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
11 Antimetabolites, Antineoplastic Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
12 Antineoplastic Agents, Alkylating Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
13 Antiviral Agents Phase 2, Phase 3,Phase 3,Early Phase 1
14 Immunosuppressive Agents Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
15 Antirheumatic Agents Phase 2, Phase 3,Phase 1,Not Applicable,Early Phase 1
16 Adjuvants, Immunologic Phase 2, Phase 3
17
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
18
Methylprednisolone Approved, Vet_approved Phase 2,Phase 1 83-43-2 6741
19
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
20
Prednisolone Approved, Vet_approved Phase 2,Phase 1 50-24-8 5755
21
Melphalan Approved Phase 1, Phase 2,Phase 2,Not Applicable,Early Phase 1 148-82-3 4053 460612
22
Thiotepa Approved, Investigational Phase 1, Phase 2,Not Applicable 52-24-4 5453
23
Mycophenolate mofetil Approved, Investigational Phase 2,Phase 1,Not Applicable 128794-94-5 5281078
24
Mycophenolic acid Approved Phase 2,Phase 1,Not Applicable 24280-93-1 446541
25
Everolimus Approved Phase 1, Phase 2 159351-69-6 6442177
26
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 5284616 6436030 46835353
27
Tacrolimus Approved, Investigational Phase 1, Phase 2,Phase 2 104987-11-3 445643 439492
28
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
29
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
30
leucovorin Approved, Nutraceutical Phase 2 58-05-9 143 6006
31 Antiemetics Phase 2,Phase 1
32 Antifungal Agents Phase 2
33 Anti-Inflammatory Agents Phase 2,Phase 1
34 Antineoplastic Agents, Hormonal Phase 2,Phase 1
35 Autonomic Agents Phase 2,Phase 1
36 Calcineurin Inhibitors Phase 2,Phase 1
37 Cyclosporins Phase 2,Phase 1
38 Dermatologic Agents Phase 2,Not Applicable
39 Folic Acid Antagonists Phase 2
40 Gastrointestinal Agents Phase 2,Phase 1
41 glucocorticoids Phase 2,Phase 1
42 Hormone Antagonists Phase 2,Phase 1
43 Hormones Phase 2,Phase 1
44 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2,Phase 1
45 Methylprednisolone acetate Phase 2,Phase 1
46 Methylprednisolone Hemisuccinate Phase 2,Phase 1
47 Neuroprotective Agents Phase 2,Phase 1
48 Nucleic Acid Synthesis Inhibitors Phase 2
49 Peripheral Nervous System Agents Phase 2,Phase 1
50 Prednisolone acetate Phase 2,Phase 1

Interventional clinical trials:

(show all 19)
# Name Status NCT ID Phase Drugs
1 Stem Cell Transplant for Bone Marrow Failure Syndromes Completed NCT00176878 Phase 2, Phase 3 Fludarabine monophosphate;Busulfan
2 Stem Cell Transplant for Hemoglobinopathy Active, not recruiting NCT00176852 Phase 2, Phase 3 Busulfan, Fludarabine, ATG, TLI;Busulfan, Cyclophosphamide, ATG, GCSF;Campath, Fludarabine, Cyclophosphamide
3 Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells Completed NCT00730314 Phase 1, Phase 2
4 Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders Completed NCT00301834 Phase 2 busulfan;cyclosporine;fludarabine phosphate;methotrexate;methylprednisolone
5 Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remi Completed NCT00305708 Phase 1, Phase 2 busulfan;fludarabine phosphate
6 Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer Recruiting NCT03333486 Phase 2 Cyclophosphamide;Fludarabine Phosphate
7 CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant Recruiting NCT02061800 Phase 1, Phase 2 Thiotepa;Cyclophosphamide;Alemtuzumab;Tacrolimus;Melphalan;Busulfan;Fludarabine;Methylprednisolone
8 Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Active, not recruiting NCT01529827 Phase 2 fludarabine phosphate;melphalan;tacrolimus;mycophenolate mofetil;methotrexate
9 Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease Completed NCT00295971 Phase 1 fludarabine phosphate;thiotepa
10 BMT Abatacept for Non-Malignant Diseases Recruiting NCT01917708 Phase 1 Abatacept
11 Screening for Genes in Patients With Congenital Neutropenia Completed NCT02866162
12 Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias Completed NCT00244010 Not Applicable
13 Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders Completed NCT00005893 Not Applicable anti-thymocyte globulin;busulfan;cyclophosphamide
14 Cancer in Inherited Bone Marrow Failure Syndromes Recruiting NCT00027274
15 CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation Recruiting NCT01966367 Early Phase 1
16 Fludarabine Based RIC for Bone Marrow Failure Syndromes Recruiting NCT02928991 Early Phase 1
17 Investigation of the Genetics of Hematologic Diseases Recruiting NCT02720679
18 Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies Recruiting NCT02179359 Not Applicable Reduced Toxicity Ablative Regimen;Reduced Intensity Preparative Regimen;Myeloablative Preparative Regimen
19 Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation Terminated NCT01319851 Not Applicable Alefacept

Search NIH Clinical Center for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Genetic Tests for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Genetic tests related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Severe Congenital Neutropenia 3, Autosomal Recessive 29 HAX1

Anatomical Context for Neutropenia, Severe Congenital, 3, Autosomal Recessive

MalaCards organs/tissues related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

41
Bone, Bone Marrow, Neutrophil, Myeloid, Liver

Publications for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Articles related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

# Title Authors Year
1
Ovarian failure in HAX1-deficient patients: is there a gender-specific difference in pubertal development in severe congenital neutropenia or Kostmann disease? ( 23050867 )
2013
2
Eponym. Kostmann disease. ( 20165869 )
2010
3
Kostmann disease with developmental delay in three patients. ( 20177699 )
2010
4
A novel missense mutation in the HAX1 gene in severe congenital neutropenia patients (Kostmann disease). ( 19796188 )
2009
5
HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). ( 17187068 )
2007
6
An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child with congenital agranulocytosis (Kostmann disease) treated with granulocyte colony-stimulating factor. Evolution towards myelodysplastic syndrome and acute basophilic leukemia. ( 8536230 )
1995

Variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 HAX1 p.Phe141Leu VAR_062259 rs179363870
2 HAX1 p.Leu130Arg VAR_064514 rs179363871
3 HAX1 p.Val172Ile VAR_064515 rs141970914

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 HAX1 NM_006118.3(HAX1): c.568C> T (p.Gln190Ter) single nucleotide variant Pathogenic rs74315322 GRCh37 Chromosome 1, 154247641: 154247641
2 HAX1 NM_006118.3(HAX1): c.568C> T (p.Gln190Ter) single nucleotide variant Pathogenic rs74315322 GRCh38 Chromosome 1, 154275165: 154275165
3 HAX1 HAX1, 1-BP INS, 130A insertion Pathogenic
4 HAX1 HAX1, 1-BP INS, 431G insertion Pathogenic
5 HAX1 HAX1, 1-BP INS, 175C insertion Pathogenic
6 HAX1 NM_006118.3(HAX1): c.256C> T (p.Arg86Ter) single nucleotide variant Pathogenic rs121908165 GRCh37 Chromosome 1, 154246014: 154246014
7 HAX1 NM_006118.3(HAX1): c.256C> T (p.Arg86Ter) single nucleotide variant Pathogenic rs121908165 GRCh38 Chromosome 1, 154273538: 154273538
8 HAX1 HAX1, 59-BP DEL, NT376 deletion Pathogenic
9 HAX1 HAX1, 1-BP INS, 121G insertion Pathogenic
10 HAX1 HAX1, 1-BP DEL, 91G deletion Pathogenic
11 HAX1 NM_006118.3(HAX1): c.207A> T (p.Pro69=) single nucleotide variant Conflicting interpretations of pathogenicity rs142150013 GRCh38 Chromosome 1, 154273489: 154273489
12 HAX1 NM_006118.3(HAX1): c.207A> T (p.Pro69=) single nucleotide variant Conflicting interpretations of pathogenicity rs142150013 GRCh37 Chromosome 1, 154245965: 154245965
13 HAX1 NM_006118.3(HAX1): c.14A> C (p.Asp5Ala) single nucleotide variant Uncertain significance rs747374340 GRCh38 Chromosome 1, 154272737: 154272737
14 HAX1 NM_006118.3(HAX1): c.14A> C (p.Asp5Ala) single nucleotide variant Uncertain significance rs747374340 GRCh37 Chromosome 1, 154245213: 154245213
15 HAX1 NM_006118.3(HAX1): c.102_104delTGA (p.Asp34del) deletion Uncertain significance GRCh37 Chromosome 1, 154245860: 154245862
16 HAX1 NM_006118.3(HAX1): c.102_104delTGA (p.Asp34del) deletion Uncertain significance GRCh38 Chromosome 1, 154273384: 154273386
17 HAX1 NM_006118.3(HAX1): c.829C> T (p.Arg277Trp) single nucleotide variant Uncertain significance rs138296453 GRCh38 Chromosome 1, 154275690: 154275690
18 HAX1 NM_006118.3(HAX1): c.829C> T (p.Arg277Trp) single nucleotide variant Uncertain significance rs138296453 GRCh37 Chromosome 1, 154248166: 154248166
19 HAX1 NM_006118.3(HAX1): c.117_122dup (p.Gly41_Gly42insGluGly) duplication Uncertain significance GRCh37 Chromosome 1, 154245875: 154245880
20 HAX1 NM_006118.3(HAX1): c.117_122dup (p.Gly41_Gly42insGluGly) duplication Uncertain significance GRCh38 Chromosome 1, 154273399: 154273404

Expression for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 3, Autosomal Recessive.

Pathways for Neutropenia, Severe Congenital, 3, Autosomal Recessive

GO Terms for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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