Pompe disease

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.