Cartilage-Hair Hypoplasia Workup

Updated: Aug 06, 2019
  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Laboratory Studies

T-cell immunodeficiency

Immunologic dysfunction occurs in approximately 86% of patients with cartilage hair-hypoplasia. [23, 32] Notarangelo et al [14] and Ip et al [12]  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 [33] 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 and defective CD25 expression. There also appears to be increased T cell apoptosis associated with increased expression of Fas, FAS ligand (FasL), proapoptotic Bax molecules, whereas expression of antiapoptotic bcl-2 and inhibitory of apoptosisi (IAP) molecules are reduced.

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. [17]   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. [33] The T- and B-cell immune function should be closely monitored, perhaps yearly.


Cyclic neutropenia is occasionally associated with cartilage-hair hypoplasia. [34] 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. [35, 36]


Imaging Studies

Radiography reveals bony scalloping, irregular sclerosis, cystic changes of the widened metaphyses, and metaphysial dysplasia in cartilage-hair hypoplasia. [19, 29, 36] 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.