Hyperbilirubinemia and Rapid Fatal Hepatic Failure in Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency (ADA-SCID)

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.

Severe Combined Immnodeficiency (SCID) - adenosin deaminase (ADA) Deficiency - hyperbilirubinemia - hepatitis - hepatic failure

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