Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S. [2] , Anmol Pitliya, M.B.B.S. M.D. [3]
Overview
Classification
Congenital defects of Phagocyte
Congenital defects of phagocyte number
Congenital defects of phagocyte function
Congeital Defects of Phagocyte Number
Congenital defects of phagocyte number
Syndrome associated
No syndrome associated
Shwachman-Diamond syndrome
Elastase deficiency (SCN1)
G6PC3 deficiency (SCN4)
HAX1 deficiency (Kostmann Disease) (SCN3)
Glycogen storage disease type 1b
GFI 1 deficiency (SCN2)
Cohen syndrome
X-linked neutropenia/myelodysplasia WAS GOF
Barth Syndrome
G-CSF receptor deficiency
Clericuzio syndrome (poikiloderma with neutropenia)
Neutropenia with combined immune deficiency
VPS45 deficiency(SCN5)
P14/LAMTOR2 deficiency
JAGN1 deficiency
methylglutacoic aciduria
SMARCD2 deficiency
WDR1 deficiency
HYOU1 deficiency
Congenital defects of phagocyte function
Congenital defects of phagocyte function
Syndrome associated
No Syndrome associated;DHR assay(or NBT test)?
Cystic Fibrosis
Normal
Abnormal
Papillion-Lefèvre
GATA2 def (MonoMac syndrome
CGD
Localized juvenile periodontitis
Specific granule deficiency
Rac 2 deficiency
B-Actin
Pulmonary alveolar proteinosis
G6PD def Class 1
Leukocyte adhesion deficiency
G6PC3 deficiency
Autosomal recessive (AR) transmission.
It is caused by homozygous or compound heterozygous mutations in the COH1 gene on chromosome 8 .
Patients present with nonprogressive psychomotor retardation, motor clumsiness, microcephaly , high-arched eyelids, short philtrum, thick hair, low hairline, hypotonia , hyperextensibility of the joints, retinochoroidal dystrophy, myopia, and granulocytopenia .[ 5]
Clericuzio syndrome (poikiloderma with neutropenia)
Autosomal recessive (AR) transmission.
It is caused by homozygous or compound heterozygous mutation in the USB1 gene on chromosome 16 .
Patients present with a gradual, centripetally spreading, papular erythematous rash on the limbs during the first year of life. Neutropenia may also be present.[ 7]
VPS45 deficiency (SCN5)
P14/LAMTOR2 deficiency
JAGN1 deficiency
WDR1 deficiency
HYOU1 deficiency
Elastase deficiency (SCN1)
HAX1 deficiency (Kostmann Disease) (SCN3)
GFI 1 deficiency
X-linked neutropenia/myelodysplasia WAS GOF
G-CSF receptor deficiency
Neutropenia with combined immune deficiency
Papillion-Lefèvre
Localized juvenile periodontitis
It is cause by a mutation in the FPR1 gene.
B-actin
It is cause by a mutation in the ACTB gene.
Patients usually develop mental retardation.
Autosomal recessive (AR) transmission.
It results from a deficiency of the beta-2 integrin subunit of the leukocyte cell adhesion molecule, which results in poor neutrophil chemotaxis and phagocytosis.
Patients develop recurrent infections, delay in umbilical cord seperation, and impaired pus formation.[ 21]
The mainstay of treatment is HSCT and gene therapy .[ 22] [ 23]
For detailed information about leukocyte adhesion deficiency, click here leukocyte adhesion deficiency
GATA2 def (MonoMac syndrome)
Autosomal dominant (AD) transmission.
This syndrome is characterized by decreased or absent circulating monocytes, dendritic cells, natural killer cells, and B cells. Patients are at increased risk of developing severe or recurrent nontuberculous mycobacterial (NTM) infections, although opportunistic fungal infections and disseminated human papillomavirus (HPV) infections also occur.[ 24] [ 25]
Bone marrow transplant has shown success as the mode of treatment in some cases. [ 26]
Specific granule deficiency
Autosomal recessive (AR) transmission.
It is cause by homozygous mutation in the CEBPE gene on chromosome 14.
Neutrophils of these patients display atypical bilobed nuclei.[ 27]
Pulmonary alveolar proteinosis
Autosomal recessive (AR) transmission.
It is caused by homozygous mutation in the CSF2RB gene on chromosome 22.
It is a rare lung disease characterized by the ineffective clearance of surfactant by alveolar macrophages causing respiratory failure.[ 28]
Chronic granulomatous disease (CGD)
X-linked recessive transmission, however it can also have autosomal recessive transmission in few cases.
It results from an inability of the phagocytes to kill microbes that they have already ingested.
Patients present with pneumonia, osteomyelitis and recurrent abscesses of the skin and organs.[ 29]
For detailed information about Chronic granulomatous disease, click here Chronic granulomatous disease
Rac 2 deficiency
It is caused by mutation in the RAC2 gene on chromosome 22.
Patients present with severe infections and impaired wound healing.[ 30]
Glucose-6-phosphate dehydrogenase deficiency (G6PD) Class 1
X-linked dominant (XLD) transmission.
It is caused by mutation in the G6PD gene on chromosome X causing decreased G6PD enzyme levels.
Patients typically present with acute hemolytic anemia and neonatal jaundice.
For detailed information about Glucose-6-phosphate dehydrogenase deficiency, click here Glucose-6-phosphate dehydrogenase deficiency
References
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↑ Kaan Boztug , Giridharan Appaswamy , Angel Ashikov , Alejandro A. Schaffer , Ulrich Salzer , Jana Diestelhorst , Manuela Germeshausen , Gudrun Brandes , Jacqueline Lee-Gossler , Fatih Noyan , Anna-Katherina Gatzke , Milen Minkov , Johann Greil , Christian Kratz , Theoni Petropoulou , Isabelle Pellier , Christine Bellanne-Chantelot , Nima Rezaei , Kirsten Monkemoller , Noha Irani-Hakimeh , Hans Bakker , Rita Gerardy-Schahn , Cornelia Zeidler , Bodo Grimbacher , Karl Welte & Christoph Klein (2009). "A syndrome with congenital neutropenia and mutations in G6PC3". The New England journal of medicine . 360 (1): 32–43. doi :10.1056/NEJMoa0805051 . PMID 19118303 .
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↑ Thierry Vilboux , Atar Lev , May Christine V. Malicdan , Amos J. Simon , Paivi Jarvinen , Tomas Racek , Jacek Puchalka , Raman Sood , Blake Carrington , Kevin Bishop , James Mullikin , Marjan Huizing , Ben Zion Garty , Eran Eyal , Baruch Wolach , Ronit Gavrieli , Amos Toren , Michalle Soudack , Osama M. Atawneh , Tatiana Babushkin , Ginette Schiby , Andrew Cullinane , Camila Avivi , Sylvie Polak-Charcon , Iris Barshack , Ninette Amariglio , Gideon Rechavi , Jutte van der Werff ten Bosch , Yair Anikster , Christoph Klein , William A. Gahl & Raz Somech (2013). "A congenital neutrophil defect syndrome associated with mutations in VPS45". The New England journal of medicine . 369 (1): 54–65. doi :10.1056/NEJMoa1301296 . PMID 23738510 .
↑ Georg Bohn , Anna Allroth , Gudrun Brandes , Jens Thiel , Erik Glocker , Alejandro A. Schaffer , Chozhavendan Rathinam , Nicole Taub , David Teis , Cornelia Zeidler , Ricardo A. Dewey , Robert Geffers , Jan Buer , Lukas A. Huber , Karl Welte , Bodo Grimbacher & Christoph Klein (2007). "A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14". Nature medicine . 13 (1): 38–45. doi :10.1038/nm1528 . PMID 17195838 .
↑ Kaan Boztug , Paivi M. Jarvinen , Elisabeth Salzer , Tomas Racek , Sebastian Monch , Wojciech Garncarz , E. Michael Gertz , Alejandro A. Schaffer , Aristotelis Antonopoulos , Stuart M. Haslam , Lena Schieck , Jacek Puchalka , Jana Diestelhorst , Giridharan Appaswamy , Brigitte Lescoeur , Roberto Giambruno , Johannes W. Bigenzahn , Ulrich Elling , Dietmar Pfeifer , Cecilia Dominguez Conde , Michael H. Albert , Karl Welte , Gudrun Brandes , Roya Sherkat , Jutte van der Werff Ten Bosch , Nima Rezaei , Amos Etzioni , Christine Bellanne-Chantelot , Giulio Superti-Furga , Josef M. Penninger , Keiryn L. Bennett , Julia von Blume , Anne Dell , Jean Donadieu & Christoph Klein (2014). "JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia". Nature genetics . 46 (9): 1021–1027. doi :10.1038/ng.3069 . PMID 25129144 .
↑ Saskia B. Wortmann , Szymon Zietkiewicz , Maria Kousi , Radek Szklarczyk , Tobias B. Haack , Soren W. Gersting , Ania C. Muntau , Aleksandar Rakovic , G. Herma Renkema , Richard J. Rodenburg , Tim M. Strom , Thomas Meitinger , M. Estela Rubio-Gozalbo , Elzbieta Chrusciel , Felix Distelmaier , Christelle Golzio , Joop H. Jansen , Clara van Karnebeek , Yolanda Lillquist , Thomas Lucke , Katrin Ounap , Riina Zordania , Joy Yaplito-Lee , Hans van Bokhoven , Johannes N. Spelbrink , Frederic M. Vaz , Mia Pras-Raves , Rafal Ploski , Ewa Pronicka , Christine Klein , Michel A. A. P. Willemsen , Arjan P. M. de Brouwer , Holger Prokisch , Nicholas Katsanis & Ron A. Wevers (2015). "CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder". American journal of human genetics . 96 (2): 245–257. doi :10.1016/j.ajhg.2014.12.013 . PMID 25597510 .
↑ H. Z. Ring , V. Vameghi-Meyers , W. Wang , G. R. Crabtree & U. Francke (1998). "Five SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) genes are dispersed in the human genome". Genomics . 51 (1): 140–143. doi :10.1006/geno.1998.5343 . PMID 9693044 .
↑ H. J. Adler , R. S. Winnicki , T. W. Gong & M. I. Lomax (1999). "A gene upregulated in the acoustically damaged chick basilar papilla encodes a novel WD40 repeat protein". Genomics . 56 (1): 59–69. doi :10.1006/geno.1998.5672 . PMID 10036186 .
↑ Douglas B. Kuhns , Danielle L. Fink , Uimook Choi , Colin Sweeney , Karen Lau , Debra Long Priel , Dara Riva , Laura Mendez , Gulbu Uzel , Alexandra F. Freeman , Kenneth N. Olivier , Victoria L. Anderson , Robin Currens , Vanessa Mackley , Allison Kang , Mehdi Al-Adeli , Emily Mace , Jordan S. Orange , Elizabeth Kang , Stephen J. Lockett , De Chen , Peter J. Steinbach , Amy P. Hsu , Kol A. Zarember , Harry L. Malech , John I. Gallin & Steven M. Holland (2016). "Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency". Blood . 128 (17): 2135–2143. doi :10.1182/blood-2016-03-706028 . PMID 27557945 .
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↑ S. E. Palmer , K. Stephens & D. C. Dale (1996). "Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis". American journal of medical genetics . 66 (4): 413–422. doi :10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L . PMID 8989458 .
↑ Manuela Germeshausen , Magda Grudzien , Cornelia Zeidler , Hengameh Abdollahpour , Sevgi Yetgin , Nima Rezaei , Matthias Ballmaier , Bodo Grimbacher , Karl Welte & Christoph Klein (2008). "Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations". Blood . 111 (10): 4954–4957. doi :10.1182/blood-2007-11-120667 . PMID 18337561 .
↑ T. Nagase , R. Kikuno , K. I. Ishikawa , M. Hirosawa & O. Ohara (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA research : an international journal for rapid publication of reports on genes and genomes . 7 (1): 65–73. PMID 10718198 .
↑ C. Lefevre , C. Blanchet-Bardon , F. Jobard , B. Bouadjar , J. F. Stalder , S. Cure , A. Hoffmann , J. F. Prud'Homme & J. Fischer (2001). "Novel point mutations, deletions, and polymorphisms in the cathepsin C gene in nine families from Europe and North Africa with Papillon-Lefevre syndrome". The Journal of investigative dermatology . 117 (6): 1657–1661. doi :10.1046/j.0022-202x.2001.01595.x . PMID 11886537 .
↑ V. Nazzaro , C. Blanchet-Bardon , C. Mimoz , J. Revuz & A. Puissant (1988). "Papillon-Lefevre syndrome. Ultrastructural study and successful treatment with acitretin". Archives of dermatology . 124 (4): 533–539. PMID 2965550 .
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↑ Jennifer Cuellar-Rodriguez , Juan Gea-Banacloche , Alexandra F. Freeman , Amy P. Hsu , Christa S. Zerbe , Katherine R. Calvo , Jennifer Wilder , Roger Kurlander , Kenneth N. Olivier , Steven M. Holland & Dennis D. Hickstein (2011). "Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency". Blood . 118 (13): 3715–3720. doi :10.1182/blood-2011-06-365049 . PMID 21816832 .
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↑ D. R. Ambruso , C. Knall , A. N. Abell , J. Panepinto , A. Kurkchubasche , G. Thurman , C. Gonzalez-Aller , A. Hiester , M. deBoer , R. J. Harbeck , R. Oyer , G. L. Johnson & D. Roos (2000). "Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation". Proceedings of the National Academy of Sciences of the United States of America . 97 (9): 4654–4659. doi :10.1073/pnas.080074897 . PMID 10758162 .