Impact of pediatric hypophosphatasia on behavioral health and quality of life

Orphanet Journal of Rare Diseases

Ryan Shanley¹  Elizabeth I. Pierpont²  Katherine J. Spurlock²  Kyriakie M. Sarafoglou³  Jill H. Simmons⁴ 

[1] Biostatistics Core, Masonic Cancer Center, University of Minnesota, 55455, Minneapolis, MN, USA;Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Avenue South, RPB 550, 55454, Minneapolis, MN, USA;Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Avenue South, RPB 550, 55454, Minneapolis, MN, USA;Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, 55455, Minneapolis, MN, USA;Department of Pediatrics, Vanderbilt University Medical Center, 37232, Nashville, TN, USA;

关键词: Hypophosphatasia;    Pediatric;    Rare bone disease;    Alkaline phosphatase;    Behavior;    Sleep disturbance;    Attention deficit hyperactivity disorder;    Quality of life;   

DOI  :  10.1186/s13023-021-01722-7

来源: Springer

【 摘 要 】

BackgroundHypophosphatasia (HPP) is a rare genetic disorder caused by loss-of-function mutations in the ALPL gene encoding tissue nonspecific alkaline phosphatase. It is characterized by defective bone mineralization associated with low alkaline phosphatase activity. Clinical features of pediatric HPP are highly variable, and can include premature loss of teeth, musculoskeletal problems, and impaired mobility. The effects of pediatric HPP on sleep, mood, regulation of attention and behavior, and other aspects of behavioral health have not been comprehensively studied.MethodsParents of 30 children with HPP (14 females, 16 males) between the ages of 3 and 16 years (mean age = 8.0 years) enrolled in this cross-sectional survey-based study. Molecular genetic and biochemical testing as well as clinical records were reviewed to verify diagnosis of HPP. The cohort included 15 patients with a more clinically severe presentation of HPP who had received treatment with enzyme replacement therapy (asfotase alfa) and 15 children with less severe HPP who were treatment-naïve. Parents provided information regarding psychopathological comorbidity, emotional and behavioral well-being, and quality of life.ResultsClinically significant behavioral health challenges were evident in 67% of children with HPP. The most common behavioral findings included sleep disturbance and symptoms of attention deficit hyperactivity disorder (ADHD), each of which were observed ≥ 50% of individuals. Sleep disturbance, pain interference, poor behavioral regulation, and mood/anxiety symptoms were associated with reduced physical and psychosocial quality of life. Behavioral concerns were evident among children with HPP receiving asfotase alfa treatment as well as among children with clinically less severe disease who had not initiated therapy. Although most children in the cohort (77%) had age-typical development of adaptive skills, emotional and behavioral challenges were associated with weaker adaptive function.ConclusionsChildren with HPP are at increased risk for ADHD symptoms and other behavioral health challenges. There is likely an under-recognition of these findings in clinical practice.

【 授权许可】

CC BY