CD55 deficiency

{{Infobox medical condition | name = | synonyms = CHAPLE Syndrome, DAF deficiency | image = Autosomal recessive - en.svg | image_size = | alt = Graphic depicting the autosomal recessive pattern of disease inheritance | image_thumbtime = | caption = CHAPLE Syndrome has an autosomal recessive pattern of inheritance | width = | image2 = | image_size2 = | alt2 = | image_thumbtime2 = | caption2 = | width2 = | pronounce = | pronounce 2 = | specialty = Medical genetics | symptoms = Gastrointestinal symptoms, edema, malnutrition, hypoalbuminemia, hypogammaglobulinemia, intestinal lymphangiectasia | complications = | onset = | duration = | types = | causes = Genetic (autosomal recessive) | risks =  | diagnosis = Genetic testing | differential = | prevention = | treatment = Eculizumab | medication = | prognosis = | frequency =  | deaths = | named after =  }}

'''CD55''' '''deficiency''', also called '''DAF deficiency''' or '''CHAPLE syndrome''', is a rare genetic disorder of the immune system. CHAPLE stands for "CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and severe protein-losing enteropathy (PLE)."<ref name="Ozen_2017">{{Cite journal |display-authors=6 |vauthors=Ozen A, Comrie WA, Ardy RC, Domínguez Conde C, Dalgic B, Beser ÖF, Morawski AR, Karakoc-Aydiner E, Tutar E, Baris S, Ozcay F, Serwas NK, Zhang Y, Matthews HF, Pittaluga S, Folio LR, Unlusoy Aksu A, McElwee JJ, Krolo A, Kiykim A, Baris Z, Gulsan M, Ogulur I, Snapper SB, Houwen RH, Leavis HL, Ertem D, Kain R, Sari S, Erkan T, Su HC, Boztug K, Lenardo MJ |date=July 2017 |title=CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis |journal=The New England Journal of Medicine |volume=377 |issue=1 |pages=52–61 |doi=10.1056/NEJMoa1615887 |pmc=6690356 |pmid=28657829}}</ref> The disorder usually manifests in childhood and can be life-threatening. This condition was described by Özen, et al. in 2017.<ref name="Ozen_2017" />

== Signs and symptoms == CHAPLE is characterized by severe protein-losing enteropathy leading to hypoproteinemia. Symptoms can include abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, and edema.<ref name="Ozen_2017" /> People also have chronic malabsorption, which causes deficiencies in iron, ferritin, calcium, magnesium, folate, vitamin D and vitamin B12.<ref name="Ozen_2017" /> Some patients may have recurrent respiratory infections associated with hypogammaglobulinemia.<ref name="Ozen_2017" /> Severe thrombotic vascular occlusions may also be found among these patients.<ref name="Ozen_2017" />

== Genetics == CHAPLE syndrome is caused by mutations of the complement regulator CD55 gene leading to a loss of protein expression.<ref name="Ozen_2017" />

=== Inheritance === CHAPLE syndrome is primarily inherited in an autosomal recessive manner.<ref name="Ozen_2017" /> This means that usually a child inherits a copy of the mutated gene from both parents, resulting in a homozygous defect.<ref>{{Cite book |title=Fetal and neonatal physiology |vauthors=Levine F |year=2017 |isbn=978-0-323-35214-7 |edition=Fifth |location=Philadelphia, PA |pages=1–13 |chapter=Basic Genetic Principles |doi=10.1016/B978-0-323-35214-7.00001-9}}</ref>

== Pathophysiology == CHAPLE syndrome is characterized by complement-mediated autoimmune hemolysis and paroxysmal nocturnal hemoglobinuria. The protein CD55 (also called decay-accelerating factor) helps to regulate the complement cascade, part of the innate immune system, by regulating the amplification phase. When CD55 is absent, the complement system attacks red blood cells and causes them to be destroyed (hemolysis).<ref>{{Cite news |title=Paroxysmal Nocturnal Hemoglobinuria (PNH) - NORD (National Organization for Rare Disorders) |url=https://rarediseases.org/physician-guide/paroxysmal-nocturnal-hemoglobinuria-pnh/ |access-date=2018-01-07 |work=NORD (National Organization for Rare Disorders)}}</ref><ref name="Brodsky 2015">{{Cite journal |vauthors=Brodsky RA |date=November 2015 |title=Complement in hemolytic anemia |journal=Blood |volume=126 |issue=22 |pages=2459–65 |doi=10.1182/blood-2015-06-640995 |pmc=11270838 |pmid=26582375 |doi-access=free}}</ref><ref name="pmid30565236">{{Cite journal |vauthors=Ozen A |date=January 2019 |title=CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease |journal=Immunological Reviews |volume=287 |issue=1 |pages=20–32 |doi=10.1111/imr.12715 |pmid=30565236 |s2cid=56478441}}</ref>

== Diagnosis == CHAPLE syndrome patients are generally diagnosed through a combination of clinical presentation, histology, and genetic testing. Although symptom presentation may vary, patients generally present with early-onset gastrointestinal symptoms, edema, malnutrition, hypoalbuminemia, and hypogammaglobulinemia.<ref name="Ozen_2017" /> Histopathological assessment of intestinal biopsy samples or resections revealed extensive lymphangiectasia, and suggest a diagnosis of primary intestinal lymphangiectasia.<ref name="Ozen_2017" /> Patients are also susceptible to large-vein thrombosis.<ref name="Ozen_2017" />

== Treatment == Once a diagnosis is made, the treatment is based on an individual's clinical condition. Kurolap and colleagues treated patients with off-label eculizumab, a humanized anti-C5 monoclonal antibody and complement inhibitor, and it was shown to have beneficial outcomes over an 18-month period.<ref>{{Cite journal |display-authors=6 |vauthors=Kurolap A, Eshach Adiv O, Hershkovitz T, Tabib A, Karbian N, Paperna T, Mory A, Vachyan A, Slijper N, Steinberg R, Zohar Y, Mevorach D, Baris Feldman H |date=March 2019 |title=Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency |journal=Journal of Pediatric Gastroenterology and Nutrition |volume=68 |issue=3 |pages=325–333 |doi=10.1097/MPG.0000000000002198 |pmid=30418410 |s2cid=53281594}}</ref> Investigators at Marmara University in Istanbul, Turkey, and the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health in Bethesda, Maryland currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.<ref>{{ClinicalTrialsGov|NCT04209634|An Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease)}}</ref> Pozelimab is the first therapeutic approved for treatment of CHAPLE disease, receiving FDA approval Aug 2023.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2023-08-18 |title=FDA approves first treatment for CD55-deficient protein-losing enteropathy (CHAPLE disease) |url=https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-cd55-deficient-protein-losing-enteropathy-chaple-disease |journal=FDA |language=en}}</ref>

== References == {{Reflist}}

Category:Rare diseases Category:Autosomal recessive disorders

{{Medical resources | ICD11 = {{ICD11|4A00.1Y}} | ICD10 =  | ICD10CM =  | ICD9 =  | ICDO = | OMIM = 226300 | MeshID = | DiseasesDB = 37691 | SNOMED CT = 1279887007 | Curlie = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | PatientUK = | NCI = | GeneReviewsNBK = | GeneReviewsName = | NORD = | GARDNum = | GARDName = | RP = | AO = | WO = | OrthoInfo = | Orphanet = | Scholia = | OB = }}