Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study.

BACKGROUND: Morquio A syndrome is a rare, autosomal recessive, progressively debilitating disorder, with multi-system impairments and high medical burden. Quebec, Canada has a large Morquio A population, which is considered unique due to the presence of founder pathogenic variants. The objectives of this study were to document the genetic and clinical heterogeneity of patients with Morquio A in Quebec, to better characterize the phenotype of those with the French Canadian founder pathogenic variant (NM_000512.5: c.1171A>G, p.Met391Val), and to describe the natural history of the patients treated with elosulfase alfa enzyme replacement therapy. Patients with Morquio A were genotyped for pathogenic variants in the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. Clinical data were retrospectively collected from medical charts of patients and included medical history, height, physical examination, respiratory function tests, electrocardiogram, echocardiogram, endurance in the 6-min walk test (6MWT), and activities of daily living (ADL) as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ). Longitudinal data were collected retrospectively and prospectively for patients treated with elosulfase alfa. RESULTS: A total of 33 patients, aged 5-63 years, were included in the analysis. Patients with the founder pathogenic variant (n = 17) generally exhibited a non-classical form of Morquio A. As compared with patients with a non-founder pathogenic variant (n = 16), these patients were generally taller, had greater endurance and were better able to perform ADL. However, they still had significant musculoskeletal disease. Most of the 26 patients treated with elosulfase alfa, regardless of pathogenic variant, showed improvements in endurance and ADL. After 5 to 12 months of treatment, the mean improvement from baseline in the 6MWT was 23% and 10 of 14 patients improved in at least one MPS-HAQ domain. Endurance and ADL generally continued to improve or maintained stable in the long term (up to 7 years). Four out of 19 treated patients with echocardiogram data at follow-up showed progression of cardiac disease. CONCLUSIONS: In Quebec, Canada, Morquio A frequently manifests as a non-classical form of the syndrome due to a founder effect. Patients treated with elosulfase alfa generally show long-term improvement or stability in endurance and function, regardless of pathogenic variant.

The shortened combined clonidine and arginine test for growth hormone deficiency is practical and specific: a diagnostic accuracy study.

BACKGROUND: The growth hormone (GH) stimulation protocols for clonidine and arginine tests are non-standardized and can be lengthy. We examined the specificity of both tests using a shorter duration of timed samples: 90 min for clonidine and 60 min for arginine. METHODS: We retrospectively studied all children who had GH stimulation with clonidine and arginine to test for GH deficiency (GHD). We compared the diagnostic accuracy of both reference and new shortened test (index). RESULTS: We reviewed 243 charts (11.4±4.1 years old; 74.5% males). The combined reference test was performed on 159 children, 29 (18.3%) tested positive for GHD on the combined index test, Kappa 0.98, false positive rate 1 (0.8%), specificity 0.99, 95th CI (0.96-1), and p=1.0. The specificity of both the clonidine and arginine single index tests was 0.98%. CONCLUSIONS: The shortened clonidine and arginine stimulation index tests have good specificity. This is a viable option for testing children for GHD.