Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation

Abstract

Short stature is characteristic of Hurler syndrome, or mucopolysaccharidosis type IH (MPS IH). Hematopoietic stem cell transplantation (HSCT) is used to treat children with MPS IH. While HSCT corrects some of the metabolic features of MPS IH, its effects on growth are not well delineated. We investigated growth in patients with MPS IH after HSCT and described accompanying endocrine abnormalities. A cohort of 48 patients with MPS IH who had received HSCT between 1983 and 2005 were included. The prevalence of short stature (height oÀ2 s.d. score, SDS) before HSCT was 9%, and increased to 71% at last follow-up (6.9±5.1 years after HSCT). Short stature was positively associated with increased age at HSCT (P ¼ 0.002) and TBI (P ¼ 0.009). In total, 23% had growth hormone deficiency and/or low insulin-like growth factor-1, one female patient had premature adrenarche, one precocious puberty and 27% had clinical or subclinical hypothyroidism. Growth failure is highly prevalent in children with MPS IH after HSCT. Children who had no TBI exposure and were younger at the time of HSCT had a better height outcome.

A Mouse Model Suggests Two Mechanisms for Thyroid Alterations in Infantile Cystinosis: Decreased Thyroglobulin Synthesis Due to Endoplasmic Reticulum Stress/Unfolded Protein Response and Impaired Lysosomal Processing

“…Subclinical hypothyroidism with elevated TSH has been reported in patients affected by Fabry disease [lysosomal galactosidase-A deficiency (76,77) and Hurler syndrome/mucopolysaccharidosis type IH (␣-L-iduronidase deficiency (78)], which are more frequent than cystinosis. However, to the best of our knowledge, their underlying thyroid physiopathology has not been explored.…”

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

“…A combination of early bone maturation, growth failure, bone growth plate disorganization, joint contractures, and endocrine abnormalities has been proposed for short stature of patients with various MPS disorders (Polgreen et al 2008;Decker et al 2010;White 2011). Growth hormone (GH)/insulin-like growth factor (IGF-1) deficiency or resistance has been reported in some patients with MPS IH (Hurler syndrome), MPS II, and MPS IIIA and in a rare case of MPS VI (Buyukgebiz et al 1995;Polgreen et al 2008;Gardner et al 2011). However, others have not observed GH/IGF-1, thyroid hormone, or pituitary-hypothalamic insufficiency (in spite of a report of empty pituitary sella) as cause(s) of growth retardation in MPS VI (Von Muhlendahl and Bradac 1975;Borges et al 2003;Decker et al 2010).…”

Growth, final height and endocrine sequelae in a UK population of patients with Hurler syndrome (MPS1H)

“…There has been one previous study of growth and endocrine function in this population (Polgreen et al 2008) who also reported evidence of short stature but were unable to comment on final adult height, instead noting that 87% of children had a height <−2SD by 10 years of age. This study did note that 27% had clinical or subclinical hypothyroidism -a finding not replicated in Fig.…”