SCN3
MCID: NTR049
MIFTS: 36

Neutropenia, Severe Congenital, 3, Autosomal Recessive (SCN3)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Rare 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:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


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 dentin dysplasia, type i. An important gene associated with Neutropenia, Severe Congenital, 3, Autosomal Recessive is HAX1 (HCLS1 Associated Protein X-1). The drugs Busulfan and Vidarabine have been mentioned in the context of this disorder. Affiliated tissues include neutrophil, bone and bone marrow, and related phenotypes are seizures and global developmental delay

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 99749Disease definitionKostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils (absolute neutrophil counts less than 500 cells/mm3) associated with frequent, recurrent bacterial infections (e.g. otitis media, pneumonia, sinusitis, urinary tract infections, abscesses of skin and/or liver) and increased promyelocytes in the bone marrow. Periodontal disease, as well as neurological symptoms, such as cognitive impairment, severe neurodegeneration and epilepsy, have been reported in some patients.Visit the Orphanet disease page for more resources.

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
Immunology:
neutropenia
recurrent bacterial infections

Neoplasia:
increased risk of leukemia
increased risk of myelodysplastic syndromes

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


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 myelodysplasia 32 HP:0002863
4 neutropenia 32 HP:0001875
5 recurrent bacterial infections 32 HP:0002718
6 leukemia 32 HP:0001909

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,Early Phase 1,Not Applicable 55-98-1 2478
2
Vidarabine Approved, Investigational Phase 2, Phase 3,Phase 3,Early Phase 1 24356-66-9 32326 21704
3
Fludarabine Approved Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1 75607-67-9, 21679-14-1 30751
4
Cyclophosphamide Approved, Investigational Phase 2, Phase 3,Phase 1,Early Phase 1,Not Applicable 6055-19-2, 50-18-0 2907
5
Lenograstim Approved, Investigational Phase 2, Phase 3 135968-09-1
6
alemtuzumab Approved, Investigational Phase 2, Phase 3,Phase 1,Early Phase 1,Not Applicable 216503-57-0
7 Immunologic Factors Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1,Not Applicable
8 Antimetabolites, Antineoplastic Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
9 Alkylating Agents Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1,Not Applicable
10 Immunosuppressive Agents Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1,Not Applicable
11 Antineoplastic Agents, Alkylating Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1,Not Applicable
12 Antiviral Agents Phase 2, Phase 3,Phase 3,Early Phase 1
13 Antimetabolites Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
14 Antilymphocyte Serum Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable
15 Anti-Infective Agents Phase 2, Phase 3,Phase 3,Early Phase 1
16 Adjuvants, Immunologic Phase 2, Phase 3
17 Antirheumatic Agents Phase 2, Phase 3,Phase 1,Early Phase 1,Not Applicable
18
Prednisolone Approved, Vet_approved Phase 2,Phase 1 50-24-8 5755
19
leucovorin Approved Phase 2 58-05-9 6006 143
20
Methylprednisolone Approved, Vet_approved Phase 2,Phase 1 83-43-2 6741
21
Methylprednisolone hemisuccinate Approved Phase 2,Phase 1 2921-57-5
22
Methotrexate Approved Phase 2 59-05-2, 1959-05-2 126941
23
Prednisolone phosphate Approved, Vet_approved Phase 2,Phase 1 302-25-0
24
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
25
Mycophenolic acid Approved Phase 2,Phase 1,Not Applicable 24280-93-1 446541
26
Melphalan Approved Phase 2,Phase 1,Not Applicable,Early Phase 1 148-82-3 4053 460612
27
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
28
Tacrolimus Approved, Investigational Phase 2,Phase 1 104987-11-3 445643 439492
29
Thiotepa Approved, Investigational Phase 1, Phase 2,Not Applicable 52-24-4 5453
30
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 46835353 6436030 5284616
31
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
32
Prednisolone hemisuccinate Experimental Phase 2,Phase 1 2920-86-7
33 Hormones Phase 2,Phase 1
34 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2,Phase 1
35 Nucleic Acid Synthesis Inhibitors Phase 2
36 Antineoplastic Agents, Hormonal Phase 2,Phase 1
37 Calcineurin Inhibitors Phase 2,Phase 1
38 Peripheral Nervous System Agents Phase 2,Phase 1
39 Antifungal Agents Phase 2
40 Vitamin B Complex Phase 2
41 Anti-Inflammatory Agents Phase 2,Phase 1
42 Folic Acid Antagonists Phase 2
43 Methylprednisolone acetate Phase 2,Phase 1
44 Folate Phase 2
45 Gastrointestinal Agents Phase 2,Phase 1
46 Prednisolone acetate Phase 2,Phase 1
47 Hormone Antagonists Phase 2,Phase 1
48 Antiemetics Phase 2,Phase 1
49 Neuroprotective Agents Phase 2,Phase 1
50 Cyclosporins 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 Remission 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 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
8 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
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 Active, not 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 Cancer in Inherited Bone Marrow Failure Syndromes Recruiting NCT00027274
14 CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation Recruiting NCT01966367 Early Phase 1
15 Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation Terminated NCT01319851 Not Applicable Alefacept
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 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

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
Neutrophil, Bone, Bone Marrow, Skin, Liver, Myeloid

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
Kostmann disease--infantile genetic agranulocytosis: historical views and new aspects. ( 12578276 )
2002
7
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 34)
# 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.514G> A (p.Val172Ile) single nucleotide variant Likely benign rs141970914 GRCh37 Chromosome 1, 154247435: 154247435
12 HAX1 NM_006118.3(HAX1): c.514G> A (p.Val172Ile) single nucleotide variant Likely benign rs141970914 GRCh38 Chromosome 1, 154274959: 154274959
13 HAX1 NM_006118.3(HAX1): c.207A> T (p.Pro69=) single nucleotide variant Conflicting interpretations of pathogenicity rs142150013 GRCh38 Chromosome 1, 154273489: 154273489
14 HAX1 NM_006118.3(HAX1): c.207A> T (p.Pro69=) single nucleotide variant Conflicting interpretations of pathogenicity rs142150013 GRCh37 Chromosome 1, 154245965: 154245965
15 HAX1 NM_006118.3(HAX1): c.91delG (p.Glu31Lysfs) deletion Pathogenic rs764082747 GRCh37 Chromosome 1, 154245849: 154245849
16 HAX1 NM_006118.3(HAX1): c.91delG (p.Glu31Lysfs) deletion Pathogenic rs764082747 GRCh38 Chromosome 1, 154273373: 154273373
17 HAX1 NM_006118.3(HAX1): c.14A> C (p.Asp5Ala) single nucleotide variant Uncertain significance rs747374340 GRCh37 Chromosome 1, 154245213: 154245213
18 HAX1 NM_006118.3(HAX1): c.14A> C (p.Asp5Ala) single nucleotide variant Uncertain significance rs747374340 GRCh38 Chromosome 1, 154272737: 154272737
19 HAX1 NM_006118.3(HAX1): c.102_104delTGA (p.Asp34del) deletion Uncertain significance GRCh37 Chromosome 1, 154245860: 154245862
20 HAX1 NM_006118.3(HAX1): c.102_104delTGA (p.Asp34del) deletion Uncertain significance GRCh38 Chromosome 1, 154273384: 154273386
21 HAX1 NM_006118.3(HAX1): c.829C> T (p.Arg277Trp) single nucleotide variant Uncertain significance rs138296453 GRCh37 Chromosome 1, 154248166: 154248166
22 HAX1 NM_006118.3(HAX1): c.829C> T (p.Arg277Trp) single nucleotide variant Uncertain significance rs138296453 GRCh38 Chromosome 1, 154275690: 154275690
23 HAX1 NM_006118.3(HAX1): c.117_122dup (p.Gly41_Gly42insGluGly) duplication Uncertain significance rs781468690 GRCh37 Chromosome 1, 154245875: 154245880
24 HAX1 NM_006118.3(HAX1): c.117_122dup (p.Gly41_Gly42insGluGly) duplication Uncertain significance rs781468690 GRCh38 Chromosome 1, 154273399: 154273404
25 HAX1 NM_006118.3(HAX1): c.376C> T (p.Arg126Trp) single nucleotide variant Uncertain significance rs765538745 GRCh37 Chromosome 1, 154246309: 154246309
26 HAX1 NM_006118.3(HAX1): c.376C> T (p.Arg126Trp) single nucleotide variant Uncertain significance rs765538745 GRCh38 Chromosome 1, 154273833: 154273833
27 HAX1 NM_006118.3(HAX1): c.383C> G (p.Ser128Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 154246316: 154246316
28 HAX1 NM_006118.3(HAX1): c.383C> G (p.Ser128Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 154273840: 154273840
29 HAX1 NM_006118.3(HAX1): c.430dup (p.Val144Glyfs) duplication Pathogenic GRCh37 Chromosome 1, 154246363: 154246363
30 HAX1 NM_006118.3(HAX1): c.430dup (p.Val144Glyfs) duplication Pathogenic GRCh38 Chromosome 1, 154273887: 154273887
31 HAX1 NM_006118.3(HAX1): c.428G> C (p.Gly143Ala) single nucleotide variant Uncertain significance rs755031266 GRCh37 Chromosome 1, 154246361: 154246361
32 HAX1 NM_006118.3(HAX1): c.428G> C (p.Gly143Ala) single nucleotide variant Uncertain significance rs755031266 GRCh38 Chromosome 1, 154273885: 154273885
33 HAX1 NM_006118.3(HAX1): c.46C> T (p.Pro16Ser) single nucleotide variant Uncertain significance rs763746492 GRCh38 Chromosome 1, 154272769: 154272769
34 HAX1 NM_006118.3(HAX1): c.46C> T (p.Pro16Ser) single nucleotide variant Uncertain significance rs763746492 GRCh37 Chromosome 1, 154245245: 154245245

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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