A 43-year-old woman with several years’ history of easy muscle fatigue.
Physical examination revealed amyotrophy and weakness of the cervical, inferior limbs and paraspinal muscles. No cardiological alterations were detected.
Blood test results showed slightly elevated serum creatin kinase (CK) and myoglobin.
MRI brain showed two periventricular lesions, without criteria for multiple sclerosis.
The gastrocnemius muscle biopsy was normal. The diagnosis was made by genetic study.
Whole MRI provided the best information about the shape, volume and tissue architecture of striated muscles.
Axial T1 and coronal T2-weighted turbo spin echo sequences were suitable for depicting atrophy of the left pectoral and left gluteus minimus muscles and anterior abdominal wall muscles, as well as fibro-fatty muscle degeneration of the right paraspinal muscle (Figs. 1-3).
Oedema was observed in the hamstring and medial gastrocnemius (predominantly left), on fat-saturated sequences (Fig. 4).
Head muscles were not involved (Fig. 5).
Pompe disease is a rare and progressive metabolic and neuromuscular disorder, which affects equally both sexes (autosomal recessive).
It is caused by a deficiency of acid α-glucosidase (GAA), which leads to an abnormal glycogen accumulation within lysosomes that fundamentally affects muscle tissue involving various systems, most notably heart, skeletal muscle, and smooth muscle [1].
There are three major forms defined according to the age of symptoms onset and the rate of disease progression [2]:
- Infantile-onset: manifests within a few months of birth. It leads to death from heart failure within the first year.
- Non-classic infantile-onset: manifests by one year of age. Most children with non-classic infantile-onset live only into early childhood. Although they present cardiac insufficiency they do not usually present infarction.
- Late onset: manifests in early or late childhood, adolescence or adulthood. It has a better prognosis than infantile-onset. They usually suffer from respiratory failure.
Although the age of presentation usually coincides with the subtype, this is not always the case, so when classifying it, other factors such as clinical presentation must be taken into account.
Therefore, depending on the muscle where the glycogen is deposited, the symptoms may include one or a few of the following [3]:
- Muscle weakness/hypotonia
- Motor delay
- Heart failure and cardiomegaly (echocardiogram may also reveal a hypertrophic left ventricle and hypertrophic septum)
- Macroglossia
- Respiratory infections
The first test to be done if Pompe disease is suspected should be the evaluation of muscle enzymes such as CK, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or lactate dehydrogenase (LDH) and urinary glucose tetrasaccharide (Glc4).
These are sensitive but non-specific markers. In fact, they do not always have to be elevated.
Muscle tissue biopsy, although more invasive, allows muscle acid-α-glucosidase activity and glycogen content to be assayed directly and rapidly [3].
Biopsy is the gold standard for diagnosing Pompe disease, as it can lead to an almost definitive diagnosis if combined with clinical and laboratory findings [4].
The diagnostic imaging technique of choice is MRI, although US and CT can also show the characteristic pattern of fatty infiltration in a fairly symmetric manner and out of proportion to the patient's age.
MRI is also useful for choosing a suitable region for muscular biopsy [5].
There are several sequences that analyze different aspects of muscle. T1-weighted imaging provide information on fat infiltration in muscle; oedema is however better detected by fat-saturated sequences.
Our case showed, as described in reference article, predominant involvement of paraspinal muscles, left pectoral muscle and abdominal muscles in head and trunk. Head muscles, upper limbs and periscapular muscles were not yet involved. In lower limbs, gluteal muscles and posterior muscles of the thighs were predominantly affected. Gluteus minimus and gluteus medius were more involved than gluteus maximus [5].
The treatment (enzyme replacement therapy and high protein diet) is effective with early diagnosis.
Defining severity of muscular infiltration is essential for prognosis and is useful for thepatient follow-up in daily clinic.
TEACHING POINTS
- Pompe disease is a rare condition that affects muscle tissue. Depending on where the glycogen is deposited the patient will have different symptoms.
- The diagnosis will be made through clinical presentation, laboratory tests, imaging and biopsy.
- MRI may be appropriately and effectively used to describe muscular changes and to choose a biopsy spot in patients with Pompe disease [5,6].
- The severity of infiltration correlates with severity of disease and can predict prognosis. That is why the diagnosis and treatment should be made as quickly as possible and treatment should be started as soon as possible [7].
Written informed patient consent for publication has been obtained.
Glycogen storage disease type II (Pompe or acid maltase deficiency disease)
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According to the provided MRI images, including transverse and coronal sequences of the chest and abdomen, the following features are observed:
• The chest transverse images show more pronounced abnormal muscle signals in the left pectoralis major muscle compared to the right side, presenting as fatty infiltration and relative muscle atrophy compared to surrounding muscle groups.
• Coronal and transverse sequences of the abdomen and pelvis indicate that the abdominal wall muscles, paraspinal (erector spinae) muscles, and muscles near the sacral region exhibit varying degrees of fatty replacement or signal abnormalities with a relatively symmetrical distribution, more pronounced than typical age-related changes.
• The lower limbs show significant involvement in the gluteal muscles (especially the gluteus medius and minimus) and the posterior thigh muscle group, manifested by high signal on T1-weighted imaging and partial atrophy.
• The cervical transverse images demonstrate mild to moderate involvement of some neck muscles, but no obvious cardiac involvement or notable cardiac structural thickening is observed.
Overall, the pattern is consistent with certain metabolic/storage myopathies, suggesting possible fatty infiltration and mild muscle atrophy.
Taking into account the patient’s history of progressive muscle weakness over many years, weakness in the neck and proximal limb muscles, and mildly elevated serum CK and myoglobin, the following conditions or differential diagnoses are considered:
1. Pompe disease (Acid α-glucosidase deficiency): An autosomal recessive metabolic disorder causing lysosomal glycogen storage in muscle. It typically involves proximal and respiratory muscles, and symmetrical fatty infiltration may be seen on MRI.
2. Partially progressive muscular dystrophy: For example, Fok muscular dystrophy. However, these usually present with a clear family history or genetic findings that may not match this patient’s profile.
3. Mitochondrial myopathy: Although it can cause muscle weakness and metabolic abnormalities, it often involves other systems (central nervous system, heart, etc.), and its imaging characteristics usually differ.
4. Inflammatory myopathy (Polymyositis, Dermatomyositis): Commonly features inflammatory edema signals on STIR and T2 fat-suppressed sequences. Although symmetrical muscle atrophy can develop over time, a chronic course without prominent inflammatory infiltration on biopsy is less characteristic.
Based on the patient’s prolonged disease course, symmetrical fatty replacement on imaging, and genetic testing results, Pompe disease is most likely.
Considering the patient’s clinical symptoms (muscle fatigue, weakness of the proximal and neck/back muscles), mildly elevated serum CK and myoglobin levels, muscle biopsy findings (no significant inflammatory or specific pathologic changes, ultimately confirmed by genetic testing), and the symmetrical involvement pattern on imaging, the most probable diagnosis is Pompe disease.
Further investigation of disease severity can include more detailed enzymatic activity tests, along with assessments of respiratory function and echocardiography.
Treatment Strategy:
• Enzyme Replacement Therapy (ERT): The primary specific treatment for Pompe disease, which can improve muscle function and slow disease progression. Early initiation can lead to better outcomes.
• Nutritional Support: A high-protein diet with careful control of carbohydrate intake, together with balanced electrolytes and vitamins, may help maintain muscle function.
• Symptomatic Management: In cases of compromised respiratory function, respiratory muscle training or non-invasive ventilatory support should be considered. For skeletal deformities or prominent tendon contractures, corrective surgery or rehabilitation care may be necessary.
Rehabilitation and Exercise Prescription (FITT-VP Principle):
1. Frequency: 2–3 sessions per week, focusing on low to moderate intensity.
2. Intensity: Based on the patient’s muscle strength and respiratory function. It is advisable to start at low to moderate intensity (e.g., keeping heart rate at 40%–60% of the maximum) to avoid excessive fatigue.
3. Time: Approximately 20–30 minutes per session with rest intervals, gradually increasing to 30–45 minutes as tolerated.
4. Type: Emphasize aerobic endurance and low-load resistance training, such as walking on flat ground or in water, gentle cycling, and light resistance exercises. Incorporate flexibility and stretching exercises.
5. Volume & Progression: As the patient adapts, progressively increase training volume and duration with regular assessments of muscle strength and respiratory status. Maintain an individualized program to avoid overtraining that could cause muscle injury.
During rehabilitation, carefully monitor respiratory status and fatigue. If chest tightness, shortness of breath, or marked fatigue occur, reduce intensity or discontinue the activity. Adjust the rehabilitation plan under professional guidance. In cases of significant muscle atrophy or limited joint range of motion, assistive devices can be used alongside guidance from a physical therapist or rehabilitation physician to gradually increase activity.
Disclaimer:
This report is based on the available information and is intended for reference only. It does not replace in-person medical diagnosis or professional physician guidance. Specific treatment and rehabilitation plans should be tailored to the patient’s condition and carried out under the comprehensive evaluation of a professional medical team.
Glycogen storage disease type II (Pompe or acid maltase deficiency disease)
