Immunodeficiency Syndrome with Hyper-IgM

In all forms of Hyper-IgM (HIGM) syndrome, the normal process of immunoglobulin heavy chain class switching from IgM to other classes fails. Patients have low to absent serum IgG, IgA and IgE with normal to elevated levels of IgM. Hyper-IgM syndrome Type 1, caused by mutations in the CD40LG gene, is by far the most common type, accounting for approximately 65-70% of HIGM cases. Type 2 (caused by mutations in AICDA) accounts for likely less than 5% of cases, while Type 3 (caused by mutations in CD40) and Type 5 (caused by mutations in UNG) account for only a small number of cases.

Hyper-IgM syndrome Types 1 and 3 are clinical similar, with patients displaying a more severe phenotype compared to Types 2 and 5. These individuals often present with severe, recurrent sinopulmonary infections, Pneumocystis jeroveci (aka Pneumocystis carinii) pneumonia (PCP), chronic diarrhea and may have intermittent or persistent neutropenia. A distinguishing feature of Types 1 and 3 is that individuals are susceptible to opportunistic infections, which is typically not observed in individuals with Types 2 or 5. In addition, individuals with Types 1 or 3 often present at an earlier age (within the first one or two years or life) as compared to individuals with Types 2 or 5, where age of onset can vary from as early as the first few years of life to even as late as the second decade.

Hyper-IgM syndrome Types 2 and 5 are also clinically similar. These individuals typically have a milder disease presentation; the most common features observed are a susceptibility to bacterial infections and lymphoid hyperplasia. One important biochemical difference between these two types is that individuals with Type 5 have normal rates of somatic hypermutation (SHM), while individuals with Type 2 typically do not have intact SHM (although mutations in a specific region of the AICDA gene can result in normal SHM frequencies).

Tests Available

Forms and Documents

Test Details

AICDA
  • Confirmation of a clinical diagnosis
  • Differential diagnosis from other types of B cell immunodeficiency
  • Carrier testing in siblings or other relatives
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

318
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 279.05 Immunodeficiency with increased IgM, Immunodeficiency with hyper-IgM: autosomal recessive X-linked
* For price inquiries please email zebras@genedx.com

References

  1. Revy P., et al, 2000. Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2), Cell 102:565-575.
  2. Kasahara Y., 2003. Hyper IgM syndrome with putative dominant negative mutation in activation-induced cytidine deaminase. J. Allergy Clin Immunol 112:755-760.
  3. Durandy A. et al., 2006. Activation-Induced Cytidine Deaminase: Structure-Function Relationship as Based on the Study of Mutants, Human Mutation 27:1185-1191.
  4. Lee, W. et al (2005) Blood 105(5):1881-1890

Forms and Documents

Test Details

CD40
  • Confirmation of a clinical diagnosis
  • Differential diagnosis from other types of B cell immunodeficiency
  • Appropriate medical management
  • Carrier testing in siblings or other relatives
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

668
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 279.05 Immunodeficiency with increased IgM, Immunodeficiency with hyper-IgM: autosomal recessive X-linked
* For price inquiries please email zebras@genedx.com

References

  1. Revy et al., (2000) Cell. 102:565-575.
  2. Kasahara et al., (2003) J. Allergy Clin Immunol. 112:755-760.
  3. Durandy et al., (2006) Human Mutation. 27:1185-1191.
  4. Lee, W. et al (2005) Blood. 105(5):1881-1890.
  5. Etzioni et al., (2004) Pediatric Research. 56(4):519-525.
  6. Durandy et al., (2006) Current Opinion in Rheumatology. 18:369-376.
  7. Ferrari et al., (2001) PNAS. 98(22):12614-12619.
  8. Mazzolari et al., (2007) Bone Marrow Transplantation. 40:279-281.
  9. Lanzi et al., (2010) Blood. 116(26):5867-5874.
  10. Imai et al., (2003) Nature Immunology. 4(10):1023-1028.
  11. Hunter et al., (2010) Haematologica. 95(3):470-475.
  12. Van Hoeyveld et al., (2007) Immunology. 120:497-201.
  13. Gilmour et al., (2003) J Clin Pathol: Mol Pathol. 56:256-262.
  14. Apoil et al., (2007) Immunology. 59:17-23.

Forms and Documents

Test Details

CD40LG
  • Confirmation of a clinical diagnosis
  • Differential diagnosis from other types of B cell immunodeficiency
  • Appropriate medical management
  • Carrier testing in siblings or other relatives
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

669
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x1
No
Yes
  • 279.05 Immunodeficiency with increased IgM, Immunodeficiency with hyper-IgM: autosomal recessive X-linked
* For price inquiries please email zebras@genedx.com

References

  1. Revy et al., (2000) Cell. 102:565-575.
  2. Kasahara et al., (2003) J. Allergy Clin Immunol. 112:755-760.
  3. Durandy et al., (2006) Human Mutation. 27:1185-1191.
  4. Lee, W. et al (2005) Blood. 105(5):1881-1890.
  5. Etzioni et al., (2004) Pediatric Research. 56(4):519-525.
  6. Durandy et al., (2006) Current Opinion in Rheumatology. 18:369-376.
  7. Ferrari et al., (2001) PNAS. 98(22):12614-12619.
  8. Mazzolari et al., (2007) Bone Marrow Transplantation. 40:279-281.
  9. Lanzi et al., (2010) Blood. 116(26):5867-5874.
  10. Imai et al., (2003) Nature Immunology. 4(10):1023-1028.
  11. Hunter et al., (2010) Haematologica. 95(3):470-475.
  12. Van Hoeyveld et al., (2007) Immunology. 120:497-201.
  13. Gilmour et al., (2003) J Clin Pathol: Mol Pathol. 56:256-262.
  14. Apoil et al., (2007) Immunology. 59:17-23.

Forms and Documents

Test Details

UNG
  • Confirmation of a clinical diagnosis
  • Differential diagnosis from other types of B cell immunodeficiency
  • Appropriate medical management
  • Carrier testing in siblings or other relatives
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

670
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 279.05 Immunodeficiency with increased IgM, Immunodeficiency with hyper-IgM: autosomal recessive X-linked
* For price inquiries please email zebras@genedx.com

References

  1. Revy et al., (2000) Cell. 102:565-575.
  2. Kasahara et al., (2003) J. Allergy Clin Immunol. 112:755-760.
  3. Durandy et al., (2006) Human Mutation. 27:1185-1191.
  4. Lee, W. et al (2005) Blood. 105(5):1881-1890.
  5. Etzioni et al., (2004) Pediatric Research. 56(4):519-525.
  6. Durandy et al., (2006) Current Opinion in Rheumatology. 18:369-376.
  7. Ferrari et al., (2001) PNAS. 98(22):12614-12619.
  8. Mazzolari et al., (2007) Bone Marrow Transplantation. 40:279-281.
  9. Lanzi et al., (2010) Blood. 116(26):5867-5874.
  10. Imai et al., (2003) Nature Immunology. 4(10):1023-1028.
  11. Hunter et al., (2010) Haematologica. 95(3):470-475.
  12. Van Hoeyveld et al., (2007) Immunology. 120:497-201.
  13. Gilmour et al., (2003) J Clin Pathol: Mol Pathol. 56:256-262.
  14. Apoil et al., (2007) Immunology. 59:17-23.