Lefever, Eveline, Witters, Peter, Gielen, Evelien et al. · Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry · 2020 · DOI
Hypophosphatasia (HPP) is a rare genetic condition affecting bone and muscle health caused by low levels of an enzyme called alkaline phosphatase. This study looked at 19 adults with HPP and found that over one-third reported fatigue, and some had been wrongly diagnosed with chronic fatigue syndrome or fibromyalgia. The study warns doctors to consider HPP when patients have unexplained fatigue and low alkaline phosphatase levels, to avoid inappropriate treatments.
This study is critical for ME/CFS patients because it documents that HPP can mimic chronic fatigue syndrome, leading to diagnostic error and potentially harmful treatments. The finding that three HPP patients were misdiagnosed with CFS/fibromyalgia highlights the importance of screening for metabolic disorders in patients with unexplained fatigue and biochemical abnormalities, which could prevent inappropriate drug exposure and guide proper management.
This study does not establish the true prevalence of HPP among patients diagnosed with ME/CFS, nor does it prove that HPP is a common cause of fatigue in the general CFS population—it only reports three misdiagnosed cases in a small specialist cohort. It cannot determine whether fatigue in HPP is directly caused by enzyme deficiency or metabolic substrates, as the study lacks mechanistic investigation. The small sample size and case-series design prevent generalization to broader populations or causal inference about diagnostic criteria.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Spotted an error in this entry? Report it →