Late-Onset Pompe's Disease
Late-Onset Pompe's Disease
The infantile form of Pompe's disease has a rather homogenous presentation, with infantile hypotonia, weakness, cardiomegaly, hepatomegaly, macroglossia, and death by 1 year of age due to respiratory failure typically occurring. Treatment with enzyme replacement therapy has drastically altered this clinical course. Conversely, the late-onset form is much more heterogeneous, with a variety of potential presentations. The age of onset of the late form can be from early childhood into adulthood, and the differential diagnosis includes essentially all of the neuromuscular disorders that produce weakness without sensory loss. The most typical presentation of the late form is the development of a slowly progressive proximal myopathy with respiratory symptoms in the second or third decade of life, but many patients vary from this typical phenotype.
Many patients with late-onset Pompe's disease present with slowly progressive proximal leg weakness. Paraspinal muscle weakness also contributes to a waddling gait, and sometimes back pain. Poor performance in sports may be noted in older children and adolescents. The shoulder girdle may also be involved. In 30% of cases, respiratory symptoms are the initial symptoms that lead to medical consultation. Diaphragm weakness causes orthopnea, dyspnea with exertion, and sleep disordered breathing. The degree of respiratory weakness is not correlated with the degree of limb weakness. The unusual presentation of a fully ambulatory patient with prominent respiratory failure is occasionally seen. Joint contractures occasionally occur. Rare alternative presentations include scapuloperoneal weakness and facial weakness. Ptosis may be present. The extramuscular manifestations typically seen in infantile Pompe's disease, macroglossia, hepatomegaly, and hypertrophic cardiomyopathy, are rare in the late-onset form. Ectasia of the cerebral arteries has recently been noted to be a frequent abnormality in late-onset Pompe's disease. There are a few reports of subarachnoid hemorrhage due to rupture of a cerebral aneurysm.
Clinical Presentation
The infantile form of Pompe's disease has a rather homogenous presentation, with infantile hypotonia, weakness, cardiomegaly, hepatomegaly, macroglossia, and death by 1 year of age due to respiratory failure typically occurring. Treatment with enzyme replacement therapy has drastically altered this clinical course. Conversely, the late-onset form is much more heterogeneous, with a variety of potential presentations. The age of onset of the late form can be from early childhood into adulthood, and the differential diagnosis includes essentially all of the neuromuscular disorders that produce weakness without sensory loss. The most typical presentation of the late form is the development of a slowly progressive proximal myopathy with respiratory symptoms in the second or third decade of life, but many patients vary from this typical phenotype.
Many patients with late-onset Pompe's disease present with slowly progressive proximal leg weakness. Paraspinal muscle weakness also contributes to a waddling gait, and sometimes back pain. Poor performance in sports may be noted in older children and adolescents. The shoulder girdle may also be involved. In 30% of cases, respiratory symptoms are the initial symptoms that lead to medical consultation. Diaphragm weakness causes orthopnea, dyspnea with exertion, and sleep disordered breathing. The degree of respiratory weakness is not correlated with the degree of limb weakness. The unusual presentation of a fully ambulatory patient with prominent respiratory failure is occasionally seen. Joint contractures occasionally occur. Rare alternative presentations include scapuloperoneal weakness and facial weakness. Ptosis may be present. The extramuscular manifestations typically seen in infantile Pompe's disease, macroglossia, hepatomegaly, and hypertrophic cardiomyopathy, are rare in the late-onset form. Ectasia of the cerebral arteries has recently been noted to be a frequent abnormality in late-onset Pompe's disease. There are a few reports of subarachnoid hemorrhage due to rupture of a cerebral aneurysm.
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