Clinical evolution of late-onset Pompe disease: a case report

Introduction. Pompe disease is an inherited metabolic myopathy due to lysosomal glycogen deposition in the absence or reduction of acid maltase enzyme activity. The worldwide prevalence of the disease ranges from 1:40,000 to 1:200,000 and it affects children and adults. Objective. This study aims to report the case of a patient diagnosed with the late form of Pompe disease. Case Report. A 44-year-old female patient had the onset of symptoms of Pompe disease at the age of 14, presenting difficulty in walking and frequent falls. The disease was diagnosed three years later. At the age of 44 and after using enzyme therapy replacement (TER) for 12 years, the clinical condition evolved into quadriplegia and involvement of the respiratory and orofacial muscles, despite the use of enzyme replacement therapy for 12 years. Conclusion. Despite the use of ERT and the care provided by a multidisciplinary team, the patient evolved with an unfavorable clinical outcome. Therefore, early diagnosis, level of enzyme activity, and response to treatment with enzyme replacement are essential for the disease prognosis.


INTRODUCTION
Pompe disease (PD), also known as acid maltase deficiency, is an autosomal recessive lysosomal storage disease that leads to the absence or reduction in the activity of the lysosomal acid alpha-glucosidase (GAA) 1 . Its worldwide prevalence is around 1:40,000 to 1:200,000 and varies in different parts of the world 2 .
Infantile-onset Pompe disease (IOPD) is the most frequent and severe form, the patients usually present symptoms at the end of the first year of life 3 . IOPD is clinically characterized by severe early-onset neonatal hypotonia, cardiomyopathy, hepatomegaly, macroglossia, and respiratory failure, these patients usually have less than 1% of GAA enzymatic activity 1 .
In Late-onset Pompe disease (LOPD), the disease manifests after the first year of life, with the onset of symptoms being more common in the third decade of life 4,5 .
In this group, the disease presents with proximal weakness, which makes a differential diagnosis especially with the autosomal recessive limb-girdle muscular dystrophies 6 .
Some particularities help to differentiate them, for example, early respiratory muscle involvement, facial and axial muscle weakness are more common in Pompe disease 6 .
Cardiomyopathy does not occur, as observed in IOPD 1 .
Also, the activity of the GAA enzyme is low, ranging from 1 to 40%, and the activity level is usually related to the precocity and severity of symptoms in the late form of the disease 6 .
Enzyme Replacement Therapy (ERT) with Alphaalglucosidase, the synthetic GAA enzyme produced in a laboratory by biotechnology that replaces the natural enzyme, is the first-line therapy for both clinical forms 1 .

DISCUSSION
Pompe disease is an underdiagnosed, rare, and serious genetic disease, especially in late-onset cases whose initial symptoms may go unnoticed for a long period or be confused with other clinical diseases and, especially with other myopathies 5,7 . Early diagnosis has important implications for the evolution of the disease and the This case report is about a patient who presented the first symptoms of PD at the age of 14, a late-onset PD that was diagnosed about 3 years after the initial symptoms.
Unfortunately, the diagnosis was confirmed and there was no specific treatment with ERT at that time, so the patient only started it at the age of 33, in the advanced stage of the disease, 16 years after the initial symptoms. The DBS showed that the patient had approximately 10% GAA enzyme activity, a considerable reduction for patients with the late form, which justifies the earlier onset of symptoms and severity among patients with LOPD 10 . Such findings are consistent with its severe course and probably with the very inadequate response to treatment with ERT. In addition, PD patients (especially in IOPD) can develop antidrug antibodies against ETR (anti-thGAA) which affect the efficacy and safety of the drug, however, the relationship between LOPD and anti-thGAA, especially regarding clinical outcomes, is unclear 11 .
Studies show that enzyme replacement adequately prevents the accumulation of glycogen in tissues, but it does not reverse tissue damage that has already been established 8 . Therefore, the diagnosis in the early stages of the disease and rapid initiation of ERT with alphaalglucosidase are essential for a less bleak prognosis. ERT showed stabilization of lung function and there was no improvement in limb muscle strength 5,8 . Other reports also show an initial trend towards improvement and/or stabilization of respiratory function and persistence of worsening in appendicular muscle strength 2,11 . The patient showed that, even with treatment, there was a progression of the disease, mainly in muscle function. To date, no extramuscular involvement by glycogen deposition has been found in the patient. It is possible that ERT was effective in maintaining and preventing injury to noncompromised organs at the beginning of the treatment, which could be considered one more reason to invest in early diagnosis and treatment. However, the clinical outcomes of LOPD patients are heterogeneous 11 . In addition, short-time ERT interruption was associated with clinical deterioration 12 .

CONCLUSION
Pompe disease is a rare, severe and progressive genetic disease, which has an effective treatment but with heterogeneous outcomes, especially considering the clinical stage at the beginning of the treatment. It is concluded that the data presented are similar to those of other authors that the diagnosis and initiation of specific treatment are fundamental for the prognosis and that is reported in the case. Although the diagnosis was rapid, the lack of specific treatment at that time, which was instituted late with the patient being clinically very compromised, was crucial for the poor outcome. Nowadays, a similar case has greater possibilities of having better results and provide a better quality of life to the patients.