Introduction

A 62-Year-Old Female with Chronic Pain, Fatigue, and Worsening Mobility

History of Present Illness

Welcome. Your patient today is Antonia R

Antonia R, a 62-year-old post-menopausal female, presents with persistent chronic joint pain, bone pain, difficulty walking long distances without taking a rest, as well as fatigue, which has progressively worsened over the years. She denies any history of fractures but reports a strong family history of similar symptoms among relatives, including her father and 2 siblings. Over the last several months, she has experienced worsening depressive symptoms, which she attributes to her declining quality of life (QOL) and chronic health struggles.

Medical History

  • Antonia struggled with activities requiring stamina and strength during childhood, such as gym class and team sports, due to pain in her bones and joints.
  • She experienced premature loss of primary dentition, followed by malalignment of permanent teeth, necessitating extensive dental interventions as an adult.
  • Chronic muscle weakness that began in adolescence was initially dismissed as “growing pains.”
  • She was diagnosed with fibromyalgia at age 54 after years of diffuse pain, difficulty walking, and fatigue, although treatment has been largely ineffective.
  • She has a longstanding history of fatigue, which she attributes to her chronic pain and poor sleep quality.
  • Antonia reports daily use of nonsteroidal anti-inflammatory drugs for several years, providing some relief for joint pain but no effect on fatigue.
  • She experienced menopause at the age of 50, has no menopausal symptoms, and is not on any hormone supplementation.
  • At the age of 50, during a routine female wellness check, Antonia R.’s laboratory results revealed a low alkaline phosphatase (ALP) level of 23 U/L; however, no further evaluation or follow-up was conducted at that time.

Antonia’s lifelong trajectory of symptoms, coupled with her family history, suggests an undiagnosed underlying condition contributing to her chronic pain, fatigue, and functional limitations. These details warrant a thorough diagnostic evaluation to identify the cause and make the appropriate diagnosis.

Family and Social History

Antonia reports a notable family history of health issues. Her father experienced chronic joint pain, which was attributed to arthritis, and also struggled with anxiety. Antonia notes that several relatives on her father’s side have dealt with progressive muscle weakness and fatigue, although no formal diagnosis was ever established.

Socially, Antonia is retired and lives alone. Previously active in her local community, she now spends less time with friends due to her chronic pain and fatigue, leading to increasing social isolation. She does not smoke, drinks alcohol socially (1–2 glasses of wine per week), and denies any history of illicit drug use.

Physical Examination Notes

Review of systems, physical examination notes and vitals

Consultation

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Transcript · Can you tell me about the main issues you’re dealing with?

Good morning, Antonia. Can you tell me about the main issues you’re dealing with?

Good morning, Doctor. The biggest things are the constant pain, the fatigue, and how hard it is to walk or even get through simple daily tasks. It’s all been getting worse over the years.

Let’s start with the pain. Can you describe what it feels like and where it’s located?

It’s a deep, aching pain that I feel mostly in my joints—my knees, hips, and back are the worst. But honestly, it’s everywhere some days, even in my muscles. It never fully goes away; sometimes it’s so bad that it keeps me awake at night.

Have you noticed anything that improves or worsens the pain?

Using anti-inflammatory medicine helps a little with the joint pain, but it doesn’t touch the muscle aches. Movement sometimes makes it worse, especially when walking or climbing stairs. Rest helps a bit, but the pain doesn’t go away completely.

Has the fatigue changed, or has it always been this severe?

It’s definitely worse now than it used to be. I’ve been tired for years, but lately, it feels like I’m always running on empty.

Transcript · What is your health like as a child?

Can you tell me a bit about your health as a child?

Sure, Doctor. I remember struggling with sports and physical activities due to bone and joint pain. I got tired quickly and always fell behind during games or activities.

Did you ever complain about pain as a child, especially in your muscles or bones?

Yes, I did. I had a lot of what they called ‘growing pains.’ My legs, especially, used to ache often, and sometimes my arms too. My parents thought it was normal, as did the doctors at the time.

How about your teeth during childhood? Did you have any issues with losing baby teeth earlier than expected or dental problems in general?

Now that you mention it, I lost some of my baby teeth really early. I also remember my adult teeth becoming crooked and needing much dental work later. My parents always thought it was just bad luck.

It’s important to note that. Did your parents or siblings ever have similar development, strength, or teeth challenges?

Yes, my dad couldn’t keep up with physical work as he got older, and my sister has complained of joint pain for years. My brother also has weak teeth.

Tests

Select appropriate tests for the patient — order and sequence are part of the exercise.

ALPL genetic test

Antinuclear antibody (ANA) test

Bone biopsy

Brief Pain Inventory

Complete blood count (CBC)

Comprehensive metabolic panel (CMP)

Dental history

Dual-energy X-ray absorptiometry (DXA scan)

Health Assessment Questionnaire

Survey of Physical and Mental Health

Thyroid function tests (TFTs)

Vitamin D and parathyroid hormone (PTH) levels

X-ray

Diagnoses

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NameAction
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Existing Diagnoses

NameStart dateEnd date
Fibromyalgia……

Case Review

This case highlights the complexity of diagnosing a rare metabolic bone disorder such as HPP. The patient’s clinical history of early primary tooth loss, chronic musculoskeletal weakness, coupled with diagnostic findings including persistently lowered ALP (see chart below), elevated vitamin B6, support a diagnosis of HPP. Although the patient’s X-ray findings were unremarkable, the clinical presentation and biochemical abnormalities are sufficient to establish a working diagnosis of HPP in this case.

Antonia’s ALP Activity over time (in blue) versus the normal age and sex adjusted range, adult

The genetic test eventually returned a positive, c. 571G>A p. (E191K) is a pathogenic variant confirming an ALPL gene mutation, further supporting the diagnosis.

Clinical pearls

Persistently Low ALP activity is a red flag, as they may indicate an underlying metabolic disorder such as HPP . ALP plays a critical role in bone mineralization , and persistently low levels may result in impaired bone metabolism, leading to symptoms such as skeletal abnormalities, fractures, and muscle weakness. Low ALP activity warrants further investigation to identify the cause and confirm the diagnosis.

You will continue to the evaluation

A 62-Year-Old Female with Chronic Pain, Fatigue, and Worsening Mobility · Or.04.24 · Antonia R

Faculty — Steven Petak MD, Richard Keen MD and Rachel Lombardo MD

Supporter — Alexion, AstraZeneca Rare Disease

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