title: DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients.
abstract: Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.
authors: Dr. von Haunersches Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors: Susanne E
authors: SE
authors: Aydin
authors: Sara Sebnem
authors: SS
authors: Kilic
authors: Caner
authors: C
authors: Aytekin
authors: Ashish
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authors: Kumar
authors: Oscar
authors: O
authors: Porras
authors: Leena
authors: L
authors: Kainulainen
authors: Larysa
authors: L
authors: Kostyuchenko
authors: Ferah
authors: F
authors: Genel
authors: Necil
authors: N
authors: Kütükcüler
authors: Neslihan
authors: N
authors: Karaca
authors: Luis
authors: L
authors: Gonzalez-Granado
authors: Jordan
authors: J
authors: Abbott
authors: Daifulah
authors: D
authors: Al-Zahrani
authors: Nima
authors: N
authors: Rezaei
authors: Zeina
authors: Z
authors: Baz
authors: Jens
authors: J
authors: Thiel
authors: Stephan
authors: S
authors: Ehl
authors: László
authors: L
authors: Marodi
authors: Jordan S
authors: JS
authors: Orange
authors: Julie
authors: J
authors: Sawalle-Belohradsky
authors: Sevgi
authors: S
authors: Keles
authors: Steven M
authors: SM
authors: Holland
authors: Özden
authors: Ö
authors: Sanal
authors: Deniz C
authors: DC
authors: Ayvaz
authors: Ilhan
authors: I
authors: Tezcan
authors: Hamoud
authors: H
authors: Al-Mousa
authors: Zobaida
authors: Z
authors: Alsum
authors: Abbas
authors: A
authors: Hawwari
authors: Ayse
authors: A
authors: Metin
authors: Susanne
authors: S
authors: Matthes-Martin
authors: Manfred
authors: M
authors: Hönig
authors: Ansgar
authors: A
authors: Schulz
authors: Capucine
authors: C
authors: Picard
authors: Vincent
authors: V
authors: Barlogis
authors: Andrew
authors: A
authors: Gennery
authors: Marianne
authors: M
authors: Ifversen
authors: Joris
authors: J
authors: van Montfrans
authors: Taco
authors: T
authors: Kuijpers
authors: Robbert
authors: R
authors: Bredius
authors: Gregor
authors: G
authors: Dückers
authors: Waleed
authors: W
authors: Al-Herz
authors: Sung-Yun
authors: SY
authors: Pai
authors: Raif
authors: R
authors: Geha
authors: Gundula
authors: G
authors: Notheis
authors: Carl-Philipp
authors: CP
authors: Schwarze
authors: Betül
authors: B
authors: Tavil
authors: Fatih
authors: F
authors: Azik
authors: Kirsten
authors: K
authors: Bienemann
authors: Bodo
authors: B
authors: Grimbacher
authors: Valerie
authors: V
authors: Heinz
authors: H Bobby
authors: HB
authors: Gaspar
authors: Roland
authors: R
authors: Aydin
authors: Beate
authors: B
authors: Hagl
authors: Benjamin
authors: B
authors: Gathmann
authors: Bernd H
authors: BH
authors: Belohradsky
authors: Hans D
authors: HD
authors: Ochs
authors: Talal
authors: T
authors: Chatila
authors: Ellen D
authors: ED
authors: Renner
authors: Helen
authors: H
authors: Su
authors: Alexandra F
authors: AF
authors: Freeman
authors: Karin
authors: K
authors: Engelhardt
authors: Michael H
authors: MH
authors: Albert
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015994:Incidence; D007223:Infant; D007239:Infections / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D007589:Job Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D010641:Phenotype; D055815:Young Adult
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E
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