U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency(SCN4)

MedGen UID:
414066
Concept ID:
C2751630
Disease or Syndrome
Synonyms: Dursun syndrome; G6PC3 Deficiency; PULMONARY ARTERIAL HYPERTENSION, LEUKOPENIA, AND ATRIAL SEPTAL DEFECT; Severe congenital neutropenia 4, autosomal recessive
SNOMED CT: Autosomal recessive severe congenital neutropenia due to glucose-6-phosphatase catalytic subunit 3 deficiency (783058007); Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (783058007); Severe congenital neutropenia type 4 (783058007); Severe congenital neutropenia, pulmonary hypertension, superficial venous angiectasis syndrome (783058007)
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).
 
Gene (location): G6PC3 (17q21.31)
 
Monarch Initiative: MONDO:0012930
OMIM®: 612541
Orphanet: ORPHA331176

Disease characteristics

Excerpted from the GeneReview: G6PC3 Deficiency
G6PC3 deficiency is characterized by severe congenital neutropenia which occurs in a phenotypic continuum that includes the following: Isolated severe congenital neutropenia (nonsyndromic). Classic G6PC3 deficiency (severe congenital neutropenia plus cardiovascular and/or urogenital abnormalities). Severe G6PC3 deficiency (classic G6PC3 deficiency plus involvement of non-myeloid hematopoietic cell lines, additional extra-hematologic features, and pulmonary hypertension; known as Dursun syndrome). Neutropenia usually presents with recurrent bacterial infections in the first few months of life. Intrauterine growth restriction (IUGR), failure to thrive (FTT), and poor postnatal growth are common. Other findings in classic and severe G6PC3 deficiency can include inflammatory bowel disease (IBD) resembling Crohn disease, and endocrine disorders (growth hormone deficiency, hypogonadotropic hypogonadism, and delayed puberty). [from GeneReviews]
Authors:
Siddharth Banka   view full author information

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Urachus fistula
MedGen UID:
488881
Concept ID:
C0345344
Congenital Abnormality
Persistence of the urachal canal with drainage of urine from the bladder through the persistent allantois canal to the umbilicus.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Broad thumb
MedGen UID:
140880
Concept ID:
C0426891
Finding
Increased thumb width without increased dorso-ventral dimension.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Triatrial heart
MedGen UID:
3238
Concept ID:
C0009995
Congenital Abnormality
The presence of an additional membrane in the left or right cardiac atrium which results in the subdivision of the affected atrium (and thus in total three atria, whence the name).
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Varicose disease
MedGen UID:
21827
Concept ID:
C0042345
Disease or Syndrome
Enlarged and tortuous veins.
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Perianal abscess
MedGen UID:
14677
Concept ID:
C0031019
Disease or Syndrome
The presence of an abscess located around the anus.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
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.
Intermittent thrombocytopenia
MedGen UID:
374151
Concept ID:
C1839167
Finding
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Otitis media
MedGen UID:
45253
Concept ID:
C0029882
Disease or Syndrome
Inflammation or infection of the middle ear.
Panniculitis
MedGen UID:
45301
Concept ID:
C0030326
Disease or Syndrome
Inflammation of adipose tissue.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Monocytosis
MedGen UID:
39091
Concept ID:
C0085702
Disease or Syndrome
An increased number of circulating monocytes.
Neonatal sepsis
MedGen UID:
96816
Concept ID:
C0456103
Disease or Syndrome
Systemic inflammatory response to infection in newborn babies.
Hypoplasia of the thymus
MedGen UID:
146347
Concept ID:
C0685891
Congenital Abnormality
Underdevelopment of the thymus.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Prominent superficial veins
MedGen UID:
324870
Concept ID:
C1837785
Finding
A condition in which superficial veins (i.e., veins just under the skin) are more conspicuous or noticable than normal.
Neonatal omphalitis
MedGen UID:
510678
Concept ID:
C0158947
Disease or Syndrome
An infection of the umbilicus and/or surrounding tissues occurring in the neonatal period.

Professional guidelines

PubMed

Arunachalam AK, Suresh H, Edison ES, Korula A, Aboobacker FN, George B, Shaji RV, Mathews V, Balasubramanian P
J Clin Pathol 2020 Jun;73(6):322-327. Epub 2019 Nov 15 doi: 10.1136/jclinpath-2019-206306. PMID: 31732620
Boztug K, Rosenberg PS, Dorda M, Banka S, Moulton T, Curtin J, Rezaei N, Corns J, Innis JW, Avci Z, Tran HC, Pellier I, Pierani P, Fruge R, Parvaneh N, Mamishi S, Mody R, Darbyshire P, Motwani J, Murray J, Buchanan GR, Newman WG, Alter BP, Boxer LA, Donadieu J, Welte K, Klein C
J Pediatr 2012 Apr;160(4):679-683.e2. Epub 2011 Nov 1 doi: 10.1016/j.jpeds.2011.09.019. PMID: 22050868

Recent clinical studies

Etiology

McKinney C, Ellison M, Briones NJ, Baroffio A, Murphy J, Tran AD, Reisz JA, D'Alessandro A, Ambruso DR
Blood Adv 2020 Dec 8;4(23):5888-5901. doi: 10.1182/bloodadvances.2020002225. PMID: 33259599Free PMC Article
Arunachalam AK, Suresh H, Edison ES, Korula A, Aboobacker FN, George B, Shaji RV, Mathews V, Balasubramanian P
J Clin Pathol 2020 Jun;73(6):322-327. Epub 2019 Nov 15 doi: 10.1136/jclinpath-2019-206306. PMID: 31732620
Boztug K, Klein C
Hematol Oncol Clin North Am 2013 Feb;27(1):43-60, vii. Epub 2012 Nov 27 doi: 10.1016/j.hoc.2012.11.004. PMID: 23351987
Boztug K, Rosenberg PS, Dorda M, Banka S, Moulton T, Curtin J, Rezaei N, Corns J, Innis JW, Avci Z, Tran HC, Pellier I, Pierani P, Fruge R, Parvaneh N, Mamishi S, Mody R, Darbyshire P, Motwani J, Murray J, Buchanan GR, Newman WG, Alter BP, Boxer LA, Donadieu J, Welte K, Klein C
J Pediatr 2012 Apr;160(4):679-683.e2. Epub 2011 Nov 1 doi: 10.1016/j.jpeds.2011.09.019. PMID: 22050868
Boztug K, Klein C
Curr Opin Pediatr 2011 Feb;23(1):21-6. doi: 10.1097/MOP.0b013e32834262f8. PMID: 21206270

Diagnosis

Velez-Tirado N, Yamazaki-Nakashimada MA, Lopez Valentín E, Partida-Gaytan A, Scheffler-Mendoza SC, Chaia Semerena GM, Alvarez-Cardona A, Suárez Gutiérrez MA, Medina Torres EA, Baeza Capetillo P, Hirschmugl T, Garncarz W, Espinosa-Padilla SE, Aguirre Hernández J, Klein C, Boztug K, Lugo Reyes SO
Scand J Immunol 2022 Apr;95(4):e13136. Epub 2022 Jan 19 doi: 10.1111/sji.13136. PMID: 34964150
Cetinkaya PG, Cagdas D, Arikoglu T, Gumruk F, Tezcan I
J Pediatr Endocrinol Metab 2020 Jul 28;33(7):957-961. doi: 10.1515/jpem-2019-0541. PMID: 32623377
Kiykim A, Baris S, Karakoc-Aydiner E, Ozen AO, Ogulur I, Bozkurt S, Ataizi CC, Boztug K, Barlan IB
J Pediatr Hematol Oncol 2015 Nov;37(8):616-22. doi: 10.1097/MPH.0000000000000441. PMID: 26479985
Banka S, Newman WG
Orphanet J Rare Dis 2013 Jun 13;8:84. doi: 10.1186/1750-1172-8-84. PMID: 23758768Free PMC Article
Banka S, Wynn R, Byers H, Arkwright PD, Newman WG
Mol Genet Metab 2013 Feb;108(2):138-41. Epub 2012 Dec 21 doi: 10.1016/j.ymgme.2012.12.001. PMID: 23298686

Therapy

McKinney C, Ellison M, Briones NJ, Baroffio A, Murphy J, Tran AD, Reisz JA, D'Alessandro A, Ambruso DR
Blood Adv 2020 Dec 8;4(23):5888-5901. doi: 10.1182/bloodadvances.2020002225. PMID: 33259599Free PMC Article
Kaya Z, Eğritaş O, Albayrak M, Göçün PU, Koçak U, Dalgiç B, Gürsel T
J Pediatr Hematol Oncol 2014 Jul;36(5):e316-8. doi: 10.1097/MPH.0000000000000079. PMID: 24322501
Estévez OA, Ortega C, Tejero Á, Fernández S, Aguado R, Aróstegui JI, González-Roca E, Peña J, Santamaría M
Pediatr Blood Cancer 2013 Jul;60(7):E29-31. Epub 2013 Feb 25 doi: 10.1002/pbc.24499. PMID: 23441086
Aytekin C, Germeshausen M, Tuygun N, Dogu F, Ikinciogullari A
J Pediatr Hematol Oncol 2013 Mar;35(2):e81-3. doi: 10.1097/MPH.0b013e3182679000. PMID: 23018568

Prognosis

Kaya Z, Eğritaş O, Albayrak M, Göçün PU, Koçak U, Dalgiç B, Gürsel T
J Pediatr Hematol Oncol 2014 Jul;36(5):e316-8. doi: 10.1097/MPH.0000000000000079. PMID: 24322501
Boztug K, Rosenberg PS, Dorda M, Banka S, Moulton T, Curtin J, Rezaei N, Corns J, Innis JW, Avci Z, Tran HC, Pellier I, Pierani P, Fruge R, Parvaneh N, Mamishi S, Mody R, Darbyshire P, Motwani J, Murray J, Buchanan GR, Newman WG, Alter BP, Boxer LA, Donadieu J, Welte K, Klein C
J Pediatr 2012 Apr;160(4):679-683.e2. Epub 2011 Nov 1 doi: 10.1016/j.jpeds.2011.09.019. PMID: 22050868

Clinical prediction guides

Yildirmak ZY, Ozcelik G, Ozagari AA, Genc DB, Onay H
J Pediatr Hematol Oncol 2022 Mar 1;44(2):e431-e433. doi: 10.1097/MPH.0000000000002237. PMID: 34224517
Boztug K, Rosenberg PS, Dorda M, Banka S, Moulton T, Curtin J, Rezaei N, Corns J, Innis JW, Avci Z, Tran HC, Pellier I, Pierani P, Fruge R, Parvaneh N, Mamishi S, Mody R, Darbyshire P, Motwani J, Murray J, Buchanan GR, Newman WG, Alter BP, Boxer LA, Donadieu J, Welte K, Klein C
J Pediatr 2012 Apr;160(4):679-683.e2. Epub 2011 Nov 1 doi: 10.1016/j.jpeds.2011.09.019. PMID: 22050868
Gatti S, Boztug K, Pedini A, Pasqualini C, Albano V, Klein C, Pierani P
J Pediatr Hematol Oncol 2011 Mar;33(2):138-40. doi: 10.1097/MPH.0b013e3181f46bf4. PMID: 21285905

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...