Abstract
Summary
Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options.
Introduction
Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP.
Methods
A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms.
Results
Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%.
Conclusions
The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.
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25 September 2018
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Juan M. Colazo, Jiun-Ruey Hu, Kathryn M. Dahir, Jill H. Simmons declare no conflicts of interest. One of the authors (JMC) is supported by NIGMS (National Institute of General Medical Sciences) of the National Institutes of Health under award number T32GM007347. The content in this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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The original version of this article was revised: The title was incorrect.
J.M Colazo and J.R Hu are sharing first authorship of this manuscript.
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Colazo, J., Hu, J., Dahir, K. et al. Neurological symptoms in Hypophosphatasia. Osteoporos Int 30, 469–480 (2019). https://doi.org/10.1007/s00198-018-4691-6
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DOI: https://doi.org/10.1007/s00198-018-4691-6