Cartilage-Hair Hypoplasia Workup

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: May 15, 2012
 

Laboratory Studies

T-cell immunodeficiency

Immunologic dysfunction occurs in approximately 86% of patients with cartilage-hair hypoplasia (CHH).[15, 21] T-cell abnormalities include lymphopenia, decreased percentages and numbers of CD3+ and CD4+ T cells, and normal percentages and numbers of B cells and natural killer (NK) cells. T-cell function is decreased, as indicated by anergy to recall antigens measured by delayed-type hypersensitivity (DTH) responses, decreased lymphoproliferative responses to mitogens (eg, phytohemagglutinin antigen [PHA], concanavalin A [Con A], pokeweed mitogen [PWM]) and to antigens.

Recently, de la Fuente et al[22] reported decreased thymopoiesis in patients with cartilage-hair hypoplasia. Recent CD4+ CD45RA+ CD31+ thymic emigrants (TE) and T-cell receptor rearrangement circles (TRECs) were reduced in cartilage-hair hypoplasia patients. T cells from cartilage-hair hypoplasia patients also demonstrated defects in cell cycle control with reduced cell divisions, increased apoptosis, and decreased lymphoproliferation. Previous studies demonstrated decreased stimulated T-cell interleukin 2 and interferon-γ synthesis.

B-cell immunodeficiency

Serum immunoglobulin levels and antibody responses to immunizations are usually normal, although a few patients with antibody deficiency have been described. Approximately 35% of patients have abnormal humoral immunity, consisting of immunoglobulin A (IgA) and/or immunoglobulin G2 (IgG2) or immunoglobulin G4 (IgG4) deficiency.[10] Although earlier studies reported that antibody responses to protein immunization were normal, data regarding bacterial polysaccharide antigens must be obtained. Occasionally, hypogammaglobulinemia consistent with common variable immunodeficiency has been described. CD27+ IgD-switched B cells are normal.[22] The T- and B-cell immune function should be closely monitored, perhaps yearly.

Anemia

Cyclic neutropenia is occasionally associated with cartilage-hair hypoplasia.[23] Megaloblastic anemia unrelated to folate and vitamin B-12 deficiency has been reported. The anemia is related to insulinlike growth factor. Fetal hemoglobulin is increased, correlating with the severity of the anemia. Over time, both the anemia and neutropenia appear to decrease in severity. Routine bone marrow examination is unnecessary. Anemia is observed in more than 80% of patients with cartilage-hair hypoplasia. Although usually mild and self-limited, some patients (9%) have severe anemia, which is permanent in one half of these patients.[24]

Next

Imaging Studies

Radiography reveals bony scalloping, irregular sclerosis, cystic changes of the widened metaphyses, and metaphysial dysplasia in cartilage-hair hypoplasia.[12, 25] Ribs display splaying of the ends at the costochondral junctions, reminiscent of vitamin D deficiency and adenosine deaminase deficiency.

Hirschsprung disease is more common in individuals with cartilage-hair hypoplasia. Appropriate radiographic studies are performed as the clinical symptoms warrant.

Previous
Next

Histologic Findings

Microscopic changes of the bones in cartilage-hair hypoplasia include clusters of hypertrophic and proliferating chondrocytes, as well as loss of normal column and trabecular formations of chondrocytes and osteoblasts. This appears as decreased cartilage.

Ossification appears normal.

Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Alan P Knutsen, MD  Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center

Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, and Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

James M Oleske  MD, MPH, François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary Allergy Immunology and Infectious Diseases, Department of Pediatrics, New Jersey Medical School; Professor, Department of Quantitative Methods, University of Medicine and Dentistry of New Jersey

James M Oleske is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of HIV Medicine, American Academy of Hospice and Palliative Medicine, American Academy of Pain Management, American Academy of Pediatrics, American Association of Pediatrics, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, American Public Health Association, American Society for Microbiology, American Thoracic Society, Arab Board of Family Medicine, Association of Clinical Researchers and Educators (ACRE), Infectious Diseases Society of America, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, National Association of Pediatric Nurse Practitioners, Pediatric Infectious Diseases Society, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

John Wilson Georgitis, MD  Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Abinun M, Kaitila I, Casanova J-L. Immunodeficiencies with associated manifestations of skin, hair, teeth, and skeleton. In: Ochs HS, Smith, CIE, Puck JM. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 2nd ed. New York, NY: Oxford University Press, Inc; 2007:513-24.

  2. McKusick VA, Eldridge R, Hostetler JA, Ruangwit U, Egeland JA. Dwarfism in the Amish. II. Cartilage-hair hypoplasia. Bull Johns Hopkins Hosp. May 1965;116:285-326. [Medline].

  3. Hermanns P, Tran A, Munivez E, et al. RMRP mutations in cartilage-hair hypoplasia. Am J Med Genet A. Oct 1 2006;140(19):2121-30. [Medline].

  4. Thiel CT, Horn D, Zabel B, et al. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet. Nov 2005;77(5):795-806. [Medline].

  5. Ridanpaa M, van Eenennaam H, Pelin K, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. Jan 26 2001;104(2):195-203. [Medline].

  6. Hirose Y, Nakashima E, Ohashi H, Mochizuki H, Bando Y, Ogata T, et al. Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia. J Hum Genet. July 2011;51:706-710. [Medline].

  7. Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A. Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum. Am J Hum Genet. September 2007;81:519-529. [Medline].

  8. Ridanpää M, Jain P, McKusick VA, Francomano CA, Kaitila I. The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases. Am J Med Genet C Semin Med Genet. August 2003;121:81-83. [Medline].

  9. Ridanpää M, Sistonen P, Rockas S, Rimoin DL, Mäkitie O, Kaitila I. Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major70A-->G mutation of the untranslated RMRP. Eur J Hum Genet. July 2002;10:439-447. [Medline].

  10. Makitie O, Kaitila I, Savilahti E. Deficiency of humoral immunity in cartilage-hair hypoplasia. J Pediatr. 2000;137:487-492.

  11. [Best Evidence] Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1):16-22. [Medline].

  12. Makitie O, Marttinen E, Kaitila I. Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients. Pediatr Radiol. 1992;22(6):434-9. [Medline].

  13. Makitie O, Kaitila I. Cartilage-hair hypoplasia--clinical manifestations in 108 Finnish patients. Eur J Pediatr. Mar 1993;152(3):211-7. [Medline].

  14. Buckley RH, Schiff RI, Schiff SE, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. Mar 1997;130(3):378-87. [Medline].

  15. Makitie O, Kaitila I, Savilahti E. Susceptibility to infections and in vitro immune function in cartilage-hair hypoplasia. Eur J Pediatr. 1998;157:816-820.

  16. Makitie O, Pukkala E, Teppo L, Kaitila I. Increased incidence of cancer in patients with cartilage-hair hypoplasia. J Pediatr. Mar 1999;134(3):315-8. [Medline].

  17. Makitie O, Kaitila I, Rintala R. Hirschsprung disease associated with severe cartilage-hair hypoplasia. J Pediatr. 2001;138:929-931.

  18. Ammann RA, Duppenthaler A, Bux J, Aebi C. Granulocyte colony-stimulating factor-responsive chronic neutropenia in cartilage-hair hypoplasia. J Pediatr Hematol Oncol. Jun 2004;26(6):379-81. [Medline].

  19. Makitie O, Kaitila I. Growth in diastrophic dysplasia. J Pediatr. Apr 1997;130(4):641-6. [Medline].

  20. Thiel CT. Cartilage-hair-hypolasia-anauexetic dysplasia spectrum disorders. In: Pagon RA, Bird TD, Dolan CR. Gene Reviews. February 2011.

  21. Kooijman R, van der Burgt CJ, Weemaes CM, et al. T cell subsets and T cell function in cartilage-hair hypoplasia. Scand J Immunol. Aug 1997;46(2):209-15. [Medline].

  22. de la Fuente MA, Recher M, Rider NL, Strauss KA, Morton DH, Adair M, et al. Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. July 2011;128:139-146. [Medline].

  23. Lux SE, Johnston RB Jr, August CS, et al. Chronic neutropenia and abnormal cellular immunity in cartilage-hair hypoplasia. N Engl J Med. Jan 29 1970;282(5):231-6. [Medline].

  24. Williams MS, Ettinger RS, Hermanns P, et al. The natural history of severe anemia in cartilage-hair hypoplasia. Am J Med Genet A. Sep 15 2005;138(1):35-40. [Medline].

  25. Glass RB, Tifft CJ. Radiologic changes in infancy in McKusick cartilage hair hypoplasia. Am J Med Genet. Oct 8 1999;86(4):312-5. [Medline].

  26. [Guideline] CDC. Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep. Mar 14 2008;57(10):258-60. [Medline].

  27. Berthet F, Siegrist CA, Ozsahin H, et al. Bone marrow transplantation in cartilage-hair hypoplasia: correction of the immunodeficiency but not of the chondrodysplasia. Eur J Pediatr. Apr 1996;155(4):286-90. [Medline].

  28. Guggenheim R, Somech R, Grunebaum E, Atkinson A, Roifman CM. Bone marrow transplantation for cartilage-hair-hypoplasia. Bone Marrow Transplant. Dec 2006;38(11):751-6. [Medline].

  29. Harada D, Yamanaka Y, Ueda K, et al. An effective case of growth hormone treatment on cartilage-hair hypoplasia. Bone. Feb 2005;36(2):317-22. [Medline].

  30. Bocca G, Weemaes CM, van der Burgt I, Otten BJ. Growth hormone treatment in cartilage-hair hypoplasia: effects on growth and the immune system. J Pediatr Endocrinol Metab. Jan 2004;17(1):47-54. [Medline].

  31. Durandy A, Wahn V, Petteway S, Gelfand EW. Immunoglobulin replacement therapy in primary antibody deficiency diseases - maximizing success. Int Arch Allergy Immunol. 2005;136:217-229.

  32. Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008;122:210-212.

  33. Garcia-Lloret M, McGhee S, Chatila TA. Immunoglobulin replacement therapy in children. Immunol Allergy Clin North Am. Nov 2008;28(4):833-49, ix. [Medline].

  34. Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. Nov 2008;28(4):765-78, viii. [Medline].

  35. Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. Aug 15 2005;62(16 Suppl 3):S5-11. [Medline].

  36. Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. 2005;62(11 Pt 2)):78S-84S.

  37. Steer CB, Szer J, Sasadeusz J, et al. Varicella-zoster infection after allogeneic bone marrow transplantation: incidence, risk factors and prevention with low-dose aciclovir and ganciclovir. Bone Marrow Transplant. Mar 2000;25(6):657-64. [Medline].

  38. Huang SW, Ammann AJ, Levy RL, Hong R, Bach FH. Treatment of severe combined immunodeficiency by a small number of pretreated nonmatched marrow cells. Transplantation. Jan 1973;15(1):174-6. [Medline].

  39. Makitie O, Pukkala E, Kaitila I. Increased mortality in cartilage-hair hypoplasia. Arch Dis Child. Jan 2001;84(1):65-67. [Medline].

  40. Makitie O, Sulisalo T, de la Chapelle A, Kaitila I. Cartilage-hair hypoplasia. J Med Genet. Jan 1995;32(1):39-43. [Medline].

  41. Makitie O, Tapanainen PJ, Dunkel L, Siimes MA. Impaired spermatogenesis: an unrecognized feature of cartilage-hair hypoplasia. Ann Med. 2001;33:201-205.

  42. Polmar SH, Pierce GF. Cartilage hair hypoplasia: immunological aspects and their clinical implications. Clin Immunol Immunopathol. Jul 1986;40(1):87-93. [Medline].

  43. Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA. Immunologic and clinical features of 25 Amish patients with RMRP 70 A-->G cartilage hair hypoplasia. Clin Immunol. April 2009;131:119-128. [Medline].

  44. Sulisalo T, Makitie O, Sistonen P, et al. Uniparental disomy in cartilage-hair hypoplasia. Eur J Hum Genet. Jan-Feb 1997;5(1):35-42. [Medline].

 
Previous
Next
 
Hair of a patient with cartilage-hair hypoplasia (left) compared with that of a typical individual. The hair of the patient with cartilage-hair hypoplasia has a smaller diameter because the central core is absent.
Table. Immune Globulin, Intravenous[33, 34, 35, 36]
Brand(Manufacturer)Manufacturing ProcesspHAdditives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs]) Parenteral Form and Final ConcentrationsIgA Content (mcg/mL)
Carimune NF



(CSL Behring)



Kistler-Nitschmann fractionation; pH 4, nanofiltration6.4-6.86% solution: 10% sucrose, < 20 mg NaCl/g proteinLyophilized powder 3%, 6%, 9%, 12%Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose free, contains 5% D-sorbitolLiquid 5%< 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25M glycineReady-for-use liquid 10%37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycineLiquid 10%46
Gammaplex



(Bio Products)



Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation 4.8-5.1Contains sorbitol (40 mg/mL); do not administer if fructose intolerantReady-for-use solution 5%< 10
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III; ultrafiltration; pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized powder 5%< 10
Polygam S/D



Gammagard S/D



(Baxter Bioscience for the American Red Cross)



Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophilized powder 5%, 10%< 1.6 (5% solution)
Octagam



(Octapharma USA)



Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration6.6Per gram of IgG: 1.67 g sucrose, < 20 mg NaClLyophilized powder 3%, 6%, 9%, 12%720
Privigen Liquid 10%



(CSL Behring)



Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration4.6-5L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)Ready-for-use liquid 10%< 25
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.