Subscribe to RSS
DOI: 10.1055/s-0030-1269916
© Georg Thieme Verlag KG Stuttgart · New York
Hyperbilirubinemia and Rapid Fatal Hepatic Failure in Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency (ADA-SCID)
Hyperbilirubinämie und fulminantes tödliches Leberversagen bei schwerem kombiniertem Immundefekt durch Adenosindeaminasemangel (ADA-SCID)Publication History
Publication Date:
26 January 2011 (online)
![](https://www.thieme-connect.de/media/klinpaed/201102/lookinside/thumbnails/10.1055-s-0030-1269916-1.jpg)
Abstract
Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T-B-NK-SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.
Zusammenfassung
Adenosindeaminasemangel (ADA-Mangel) ist bei 15% aller Patienten mit schwerem kombiniertem Immundefekt (SCID) ursächlich für die Erkrankung und präsentiert sich üblicherweise als T-B-NK-SCID. Behandlungsoptionen für ADA-Mangel sind Enzymersatztherapie, Knochenmarktransplantation und Gentherapie. Wir beschreiben hier den ersten Patienten mit ADA-SCID und tödlichem Leberversagen trotz Knochenmarktransplantation von einem 10/10 HLA-identen verwandten Spender. Da Patienten mit ADA-SCID einem bisher unterschätzten Risiko für ein fulminantes Leberversagen ausgesetzt sein könnten, regen wir an, dass die Diagnose einer Hepatitis bei ADA-SCID-Patienten zum sofortigen Beginn einer Enyzmersatztherapie mit pegyliertem ADA führen sollte.
Key words
Severe Combined Immnodeficiency (SCID) - adenosin deaminase (ADA) Deficiency - hyperbilirubinemia - hepatitis - hepatic failure
Schlüsselwörter
schwerer kombinierter Immundefekt (SCID) - Adenosindeaminase-(ADA-) Defekt - Hyperbilirubinämie - Hepatitis - Leberversagen
References
- 1 Agarwal R, Sagar S, Parks R. Adenosine Deaminase from human erythrocytes: Purification and effects of Adenosine Analogs. Biochem Pharmacol. 1975; 24 693-701
- 2 Antoine C, Muller S, Cant A. et al . Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–1999. Lancet. 2003; 361 553-560
- 3 Arredondo-Vega FX, Santisteban I, Daniels S. et al . Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. Am J Hum Genet. 1998; 63 1049-1059
- 4 Blackburn MR, Datta SK, Kellems RE. Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency. J Biol Chem. 1998; 273 5093-5100
- 5 Blackburn MR, Kellems RE. Adenosine deaminase deficiency: metabolic basis of immune deficiency and pulmonary inflammation. Adv Immunol. 2005; 86 1-41
- 6 Bollinger ME, Arredondo-Vega FX, Santisteban I. et al . Brief report: hepatic dysfunction as a complication of adenosine deaminase deficiency. N Engl J Med. 1996; 334 1367-1371
- 7 Booth C, Gaspar HB. Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID). Biologics. 2009; 3 349-358
- 8 Booth C, Hershfield M, Notarangelo L. et al . Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin Immunol. 2007; 123 139-147
- 9 Cederbaum SD, Kaitila I, Rimoin DL. et al . The chondro-osseous dysplasia of adenosine deaminase deficiency with severe combined immunodeficiency. J Pediatr. 1976; 89 737-742
- 10 Fischer A, Le Deist F, Hacein-Bey-Abina S. et al . Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005; 203 98-109
- 11 Gaspar HB, Aiuti A, Porta F. et al . How I treat ADA deficiency. Blood. 2009; 114 3524-3532
- 12 Giblett ER, Anderson JE, Cohen F. et al . Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972; 2 1067-1069
- 13 Hershfield MS. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr Opin Immunol. 2003; 15 571-577
- 14 Hershfield MS. New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eur J Immunol. 2005; 35 25-30
- 15 Honig M, Albert MH, Schulz A. et al . Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. Blood. 2007; 109 3595-3602
- 16 Honig M, Thiel J, Warnatz K. et al . Congenital T and B lymphocyte deficiencies. Monatsschr Kinderheilkd. 2009; 157 853-860
- 17 Markert ML. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991; 3 45-81
- 18 Migchielsen AA, Breuer ML, Hershfield MS. et al . Full genetic rescue of adenosine deaminase-deficient mice through introduction of the human gene. Hum Mol Genet. 1996; 5 1523-1532
- 19 Ozsahin H, Arredondo-Vega FX, Santisteban I. et al . Adenosine deaminase deficiency in adults. Blood. 1997; 89 2849-2855
- 20 Ratech H, Greco MA, Gallo G. et al . Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations. Am J Pathol. 1985; 120 157-169
- 21 Rossberg S, Schwarz K, Meisel C. et al . Delayed onset of (severe) combined immunodeficiency (S)CID (T-B+NK+): complete IL-7 receptor deficiency in a 22 months old girl. Klin Padiatr. 2009; 221 339-343
- 22 Sauer AV, Mrak E, Hernandez RJ. et al . ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood. 2009; 114 3216-3226
- 23 Wakamiya M, Blackburn MR, Jurecic R. et al . Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice. Proc Natl Acad Sci U S A. 1995; 92 3673-3677
Correspondence
PD Dr. Horst von Bernuth
University Hospital Berlin
Department for Pediatric
Pneumology and Immunology
Augustenburger Platz 1
13353 Berlin
Germany
Phone: +49/30/450 666 384
Fax: +49/30/450 566 938
Email: horst.von-bernuth@charite.de