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Cartilage-Hair Hypoplasia Workup

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
Updated: Jun 08, 2016

Laboratory Studies

T-cell immunodeficiency

Immunologic dysfunction occurs in approximately 86% of patients with cartilage hair-hypoplasia.[17, 23] Recently, Notarangelo et al[10] and Kavadas et al[11] reported on the heterogeneity of the immunodeficiency. The immunodeficiency predominantly affects T-cell immunity.

Lymphopenia and decreased CD3+, CD4+, and CD8+ T cells present in early infancy. There may be a selective decrease of CD8+ T cells. Skewing of TCRab repertoire may be present.

T cell lymphoproliferative responses to mitogens such as phytohemagglutinin ([PHA], concanavalin A [Con A], and pokeweed mitogen [PWM] and to antigens such as Candidaalbicans and tetanus toxoid may be decreased.

Delayed-type hypersensitivity (DTH) responses to recall antigens are absent, anergic. de la Fuente et al[24] reported decreased CD4+ CD45RA+ CD31+ –naïve T cells in patients with cartilage hair-hypoplasia. In addition, T-cell receptor rearrangement circles (TRECs) were reduced in cartilage hair-hypoplasia patients, indicating decreased thymopoiesis.

T cells from cartilage hair-hypoplasia patients also demonstrated defects in cell cycle control with reduced cell divisions and increased apoptosis.

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.[12] 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.[24] The T- and B-cell immune function should be closely monitored, perhaps yearly.


Cyclic neutropenia is occasionally associated with cartilage-hair hypoplasia.[25] 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.[26]


Imaging Studies

Radiography reveals bony scalloping, irregular sclerosis, cystic changes of the widened metaphyses, and metaphysial dysplasia in cartilage-hair hypoplasia.[14, 27] 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.


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.

Contributor Information and Disclosures

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, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

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 Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

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

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

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.

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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 [38, 39, 40, 41]
Brand(Manufacturer) Manufacturing Process pH Additives (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 Concentrations IgA Content (mcg/mL)
Carimune NF

(CSL Behring)

Kistler-Nitschmann fractionation; pH 4, nanofiltration 6.4-6.8 6% solution: 10% sucrose, < 20 mg NaCl/g protein Lyophilized powder 3%, 6%, 9%, 12% Trace

(Grifols USA)

Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization 5.1-6 Sucrose free, contains 5% D-sorbitol Liquid 5% < 50
Gammagard Liquid 10%

(Baxter Bioscience)

Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.1 0.25M glycine Ready-for-use liquid 10% 37

(Talecris Biotherapeutics)

Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation 4-4.5 Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine Liquid 10% 46

(Bio Products)

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

(Baxter Bioscience)

Cohn-Oncley fraction II/III; ultrafiltration; pasteurization 6.4-7.2 5% solution: 5% glucose, 0.3% NaCl Lyophilized 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 6.4-7.2 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose Lyophilized powder 5%, 10% < 1.6 (5% solution)

(Octapharma USA)

Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization 5.1-6 10% maltose Liquid 5% 200

(Swiss Red Cross for the American Red Cross)

Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration 6.6 Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl Lyophilized 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 filtration 4.6-5 L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) Ready-for-use liquid 10% < 25
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