Fujiwara, Shintaro, Otsuka, Yuki, Furukawa, Masanori et al. · Journal of clinical medicine · 2024 · DOI
This study looked at blood test results from over 50,000 patients to find out how common persistently low alkaline phosphatase (an enzyme in the blood) is and what causes it. Researchers found that about 0.5% of patients had persistently low levels, and identified cancer, steroid use, and immunosuppressant medications as the main causes. Importantly, 14% of patients with low alkaline phosphatase had no clear explanation, and some of these patients had symptoms like chronic pain, muscle weakness, and fatigue that could indicate a rare bone disease called hypophosphatasia.
While this study does not directly address ME/CFS, it is relevant because unexplained persistent hypophosphatasemia may indicate undiagnosed hypophosphatasia—a rare metabolic bone disease that can present with chronic pain, muscle weakness, and fatigue that overlap with ME/CFS symptoms. ME/CFS patients with these symptoms and incidental low alkaline phosphatase levels should be evaluated for this treatable condition. Identifying previously missed diagnoses in patients with chronic unexplained symptoms is important for ensuring appropriate care and avoiding prolonged misdiagnosis.
This study does not establish a causal relationship between low alkaline phosphatase and ME/CFS, nor does it prove that hypophosphatasia is common in ME/CFS populations. The study is descriptive and cannot determine whether symptoms in the 14% of unexplained cases are actually due to hypophosphatasia without confirmatory genetic or enzymatic testing. The findings are from a single Japanese hospital and may not generalize to other populations or healthcare systems.
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 →
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