Clinical Characteristics of Persistent Hypophosphatasemia ... in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital 2024 Fujiwara+

Abstract

Background: Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition.

Methods: In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged ≥18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (≤40 IU/L) for 28 days with a minimum recorded level of ≤35 IU/L.

Results: Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, p < 0.01) and had a younger median age (51 years vs. 63 years; Mann–Whitney U test, p < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia.

Conclusions: This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition.

Open access, https://www.mdpi.com/2077-0383/13/23/7078

 

"Category 3 included 12 patients with chronic fatigue syndrome or muscle, bone, and joint pain in the extremities. All of those patients underwent a screening blood test for thyroid and adrenal endocrine functions, as well as collagen disease, resulting in no diagnosis."

"Category 3: Twelve patients in this category experienced muscle, bone, and joint pain in the extremities or back, as well as muscle weakness. Over half of these patients were diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition characterized by persistent extreme tiredness. Although the etiology of ME/CFS remains elusive, it can affect multiple body systems. Patients with CFS or those complaining of chronic pain in this category were prescribed symptomatic herbal and other medications. Interestingly, since ME/CFS is partly associated with elevated ALP levels [33], the presence of persistent hypophosphatasemia along with chronic pain and muscle weakness in these patients suggests adult HPP as a potential diagnosis."

They don't detail the criteria for diagnosing ME/CFS.

 

I think this paper is very confusing. Anyone following up on it should be careful they've really found what they wanted. All the info I've copied comes from wikipedia.

Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calcium blood levels, which can result in muscle spasms.

Hypophosphatasia also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbun's syndrome; sometimes abbreviated HPP is a rare, and sometimes fatal, inherited metabolic bone disease.

Hypophosphatasemia (as used mostly in the paper, along with a couple of uses of hyphosphatasia) seems to be being used as a name for a deficiency of alkaline phosphatase, but I can't find it listed anywhere and it seems to be used exclusively in the paper.

Can someone correct me if I've got things muddled up.