eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Cartilage-Hair Hypoplasia: Differential Diagnoses & Workup

Author: Alan P Knutsen, MD, Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center
Contributor Information and Disclosures

Updated: May 19, 2009

Differential Diagnoses

B-Cell and T-Cell Combined Disorders

Other Problems to Be Considered

Other forms of short-limb dwarfism may also have an associated immunodeficiency, including isolated T-cell defects, isolated B-cell defects, or combined T-cell and B-cell defects. The hair abnormality distinguishes cartilage-hair hypoplasia (CHH) from other forms of short-limb dwarfism.

Although adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency cause skeletal and immune defects, neither is associated with dwarfism.

Workup

Laboratory Studies

  • T-cell immunodeficiency: Immunologic dysfunction occurs in approximately 86% of patients with cartilage-hair hypoplasia (CHH).11,16  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. Serum immunoglobulin levels and antibody responses to immunizations are usually normal, although a few patients with antibody deficiency have been described.
  • B-cell immunodeficiency: Approximately 35% of patients have abnormal humoral immunity, consisting of immunoglobulin A (IgA) and/or immunoglobulin G2 (IgG2) or immunoglobulin G4 (IgG4) deficiency.5  Although earlier studies reported that antibody responses to protein immunization were normal, data regarding bacterial polysaccharide antigens must be obtained. The T-cell and B-cell immune function should be closely monitored, perhaps on a yearly basis.
  • Anemia: Cyclic neutropenia is occasionally associated with cartilage-hair hypoplasia.17 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.18

Imaging Studies

  • Radiography reveals bony scalloping, irregular sclerosis, cystic changes of the widened metaphyses, and metaphysial dysplasia in cartilage-hair hypoplasia.8,19 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.

More on Cartilage-Hair Hypoplasia

Overview: Cartilage-Hair Hypoplasia
Differential Diagnoses & Workup: Cartilage-Hair Hypoplasia
Treatment & Medication: Cartilage-Hair Hypoplasia
Follow-up: Cartilage-Hair Hypoplasia
Multimedia: Cartilage-Hair Hypoplasia
References
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References

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Further Reading

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Keywords

cartilage-hair hypoplasia, CHH, short-limb dwarfism, metaphyseal dysplasia, spondyloepiphyseal dysplasia, immunodeficiency, metaphyseal chondrodysplasia McKusick type, T-cell immunodeficiency, isolated B-cell immunodeficiency, varicella infection, severe combined immunodeficiency, SCID, leukemia, lymphoma, graft versus host disease, non-Hodgkin lymphoma, basal cell carcinoma, anal stenosis, esophageal atresia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Alan P Knutsen, MD, Professor of Pediatrics, Director of Pediatric Allergy and Immunology, 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 and Clinical Immunology Society
Disclosure: Nothing to disclose.

Medical Editor

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
James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
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, UMDNJ-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.

 
 
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