Cartilage-Hair Hypoplasia

Abstract

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive metaphyseal chondrodysplasia seen primarily in people of Amish and Finnish origin. It is characterized by disproportionately short stature; limb deformities; fine, sparse, light-colored hair; and immunodeficiency.1Makitie O Kaitila I Cartilage-hair hypoplasia—clinical manifestations in 108 Finnish patients.Eur J Pediatr. 1993; 152: 211-217Crossref PubMed Scopus (156) Google Scholar The aberrant gene was recently mapped to chromosome 9p21-p13 (the ribonuclease mitochondrial RNA processing [RMRP] gene).2Ridanpaa 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. 2001; 104: 195-203Abstract Full Text Full Text PDF PubMed Scopus (368) Google Scholar The immunologic deficiency in CHH affects primarily the T-cell system but may also involve humoral immunity.3Pierce GF Polmar SH Lymphocyte dysfunction in cartilage-hair hypoplasia: evidence for an intrinsic defect in cellular proliferation.J Immunol. 1982; 129: 570-575PubMed Google Scholar, 4Makitie O Kaitila I Savilahti E Deficiency of humoral immunity in cartilage-hair hypoplasia.J Pediatr. 2000; 137: 487-492Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Patients with CHH are prone to certain viruses, including varicella, poliovirus, and vaccinia. They also have an increased risk of malignancies.5Makitie O Kaitila I Savilahti E Susceptibility to infections and in vitro immune functions in cartilage-hair hypoplasia.Eur J Pediatr. 1998; 157: 816-820Crossref PubMed Scopus (68) Google Scholar A 39-year-old man with a history of dwarfism first presented with recurrent respiratory infections, allergies, and chronic cough. He experienced chronic sinusitis and recurrent pneumonias that required antibiotics and sinus surgery. Physical examination findings were notable for short stature (114 cm) with typical skeletal deformities; very fine, light-colored hair; serous otitis media; expiratory rattles; and 2 warts on his left hand. Computed tomography of the chest revealed central bronchiectasis. Moderate lymphopenia was identified, with decreased counts in all subpopulations except natural killer cells. Diminished mitogen-induced blastogenesis was evident. Natural killer cell and neutrophil function were normal. Although CHH predominantly affects cellular immunity, our patient had a profound humoral deficit with remarkably low IgG2, IgG3, and IgG4 subclass levels despite a high-normal total IgG level. His response to pneumococcal polysaccharide was extremely limited. Genomic DNA analysis characterized the patient as compound heterozygotic, with 2 changes in the RMRP gene. Initial treatment with an alternating regimen of antibiotics resulted in improvement. After administration of intravenous immunoglobulin, antibiotics were discontinued with sustained clinical benefit.