Multisystem late onset Pompe disease (LOPD): an update on clinical aspects

Abstract

Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression in two main forms: the first one, infantile onset Pompe disease (IOPD), presents before the age of 12 months with generalized muscle weakness, hypotonia, respiratory distress, and hypertrophic cardiomyopathy as main clinical features. The second form, late onset Pompe disease (LOPD), is characterized by an onset at the age of 12 months to adulthood, hyperCKemia, and limb-girdle and axial muscle weakness, often complicated by respiratory muscles degeneration. In the last 10-15 years, an increasing interest in Pompe disease has led to multiple studies in an effort to clarify the emerging clinical aspects, to find out the best diagnostic tools to identify the disease as early as possible, and to offer new therapeutic options apart from enzyme replacement therapy (ERT). Since 2006, ERT-the first treatment for Pompe disease-has been universally accepted in the majority of countries all over the world. Although for years Pompe disease has been primarily considered a muscle disorder, nowadays it is clear that the involvement of several other organs has changed the cultural approach to this entity which is now viewed as a multisystem disorder. The emerging clinical aspects have greatly expanded the spectrum of the disease manifestations. In fact, central, peripheral, and autonomous nervous systems are often involved; vascular malformations and heart involvement are frequently observed; musculoskeletal and bone changes as well as oro-gastrointestinal and urinary tract alterations have been better defined. A great deal of effort has been made to clarify the clinical aspects of Pompe disease, to raise awareness of the LOPD patients' problems and to improve their quality of life.

Keywords: Late onset Pompe disease presentation (LOPD presentation); Pompe disease; aneurysms; hyperCKemia; myopathy.

Figure 1

The LOPD “triangle” of clinical presentations. LOPD, late onset Pompe disease.

Figure 2

LOPD clinical aspects. (A) Unilateral eyelid ptosis in a 64-year-old LOPD female; (B) scapular winging in a 55-year-old LOPD man; (C) positive Gower’s manoeuvre in a 48-year-old LOPD female. LOPD, late onset Pompe disease.

Figure 3

Brain imaging in LOPD. (A) CT-scan showing a vertebral dolichoectasia in a 64-year-old LOPD female; (B) T2 weighted scan showing a lacunar encephalopathy (Fazekas score 2). LOPD, late onset Pompe disease.