A 30-Year Prospective Follow-Up Study Reveals Risk Factors for Early Death in Cartilage-Hair Hypoplasia

Abstract

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985–1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% ( n = 15) and 24% ( n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3–11); most commonly from malignancy ( n = 7, SMR = 10, 95%CI = 4.1–21) and lung disease ( n = 4, SMR = 46, 95%CI = 9.5–130). Mortality associated with birth length below −4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5–20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3–11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04–55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3–43/2.6–140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5–430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.

Outcomes of 42 pregnancies in 14 women with cartilage-hair hypoplasia: a retrospective cohort study

“…The interview and questionnaire covered pregnancy-related issues such as the number and outcome of pregnancies, pregnancy complications, pregnancy weeks (pw) at delivery, mode of delivery, delivery and post-partum complications and birth weight (BW), birth length (BL) and Apgar score of the newborns. Medical records of maternal outcomes were reviewed for all women, whereas offspring's medical records were obtained only with a separate permission given by 9 of the 14 women and involving 19 children.…”

How Altered Ribosome Production Can Cause or Contribute to Human Disease: The Spectrum of Ribosomopathies

“…This pleiotropic disorder is characterized by short-limbed dwarfism, sparse hypoplastic hair, defective T-cell immunity, hypoplastic anemia, increased risk of developing malignancies [ 90 , 91 ], and other symptoms [ 92 , 93 , 94 , 95 ]. Many of these symptoms, including immunodeficiency and cancer predisposition, are considered responsible for a shorter life expectancy in these patients [ 96 ]. In 2001, the study by Ridanpaa et al [ 8 ] first described how mutations in the RMRP (RNA component of RNase MRP) gene are the molecular cause for CHH.…”

The Safety and Efficacy of Live Viral Vaccines in Patients With Cartilage-Hair Hypoplasia

“…Clinical data, including data on live-vaccine preventable diseases, were obtained from the patients directly, as well as retrospectively from health records, as part of our previous studies exploring characteristics and natural course of CHH in the Finnish cohort (5,13,20,21). Only provider-recorded data in the patients' immunization certificates were considered reliable and were included in the analysis of immunizations.…”

“…Only provider-recorded data in the patients' immunization certificates were considered reliable and were included in the analysis of immunizations. The researchers had access to data on all hospitalizations of the study patients, beginning from 1969, via the Health Registers described in detail previously (21).…”