Early treatment of infantile-onset Pompe Disease
Pompe Disease is characterised by a deficiency of acid α-glucosidase (GAA). The GAA enzyme degrades lysosomal glycogen, and insufficient GAA activity causes glycogen to accumulate in various tissues.
Accumulation of lysosomal glycogen in cardiac muscle and skeletal muscle causes progressive cardiomyopathy and generalised muscle weakness and hypotonia, resulting in severely delayed motor development.1 In the absence of treatment, the life expectancy of infants with Pompe Disease is usually < 1 year with death typically caused by cardiorespiratory failure. 2-4
Associate Professor Robert G. Weintraub, Cardiologist at the Royal Children's Hospital, Melbourne, has research interests in cardiomyopathy, and Pompe Disease:
"The cardiac manifestations of infantile-onset Pompe Disease can include both hypertrophic and dilated cardiomyopathy and, often a combination of the two. The cardiac signs and symptoms, which include both tachypnoea and overt congestive heart failure, may sometimes precede the overt somatic manifestations. The electrocardiogram typically shows a short PR interval with large voltage QRS complexes. Echocardiography shows varying combinations of left ventricular hypertrophy and dilatation with reduced systolic function. Early onset Pompe Disease needs to be considered in the differential diagnosis of infants with both hypertrophic and dilated cardiomyopathy."
Enzyme Replacement Therapy
Recent data 5 confirmed the clinical benefits in infantile-onset Pompe Disease of enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA, Myozme). Results showed improved survival, respiratory function, cardiomyopathy and, among a subset of patients, motor function, compared with an untreated historical control group of infants aged < 7 months exhibiting cardiomyopathy and profound GAA deficiency. 5
In an extension of the 52-week trial, sixteen of the original eighteen children received ERT at either 20 mg/kg biweekly (n= 8) or 40 mg/kg biweekly (n= 8) for up to 3 years. These children continued to exhibit the benefits of ERT at age 36 months. Over the entire study period, ERT reduced:
• Risk of death by 95%
• Risk of invasive ventilation or death by 91%
• Risk of any type of ventilation or death by 87%.1
The clinical timing of enzyme replacement therapy in infantile-onset Pompe disease plays a vital role in survival outcomes. Early enzyme replacement therapy, commenced no later than 5 months of age in patients with Pompe disease is useful in the management of cardiac dysfuntion.6
A/Professor Weintraub is familiar with the current literature and recommends initiating early ERT. “The use of myozyme replacement therapy can modify and often significantly reverse the cardiac manifestations of Pompe Disease. In order to be effective, this therapy has to be started early. Infants with an advanced dilated cardiomyopathy are at particular risk and tend to have worse outcomes.”
References
1. Kishnani PS et al. Pediatr Res 2009;66(3):329-335. 2. Van den Hout HM et al. Pediatrics 2003;112:332-340. 3. Slonim AE et al J Pediatr 2000;137:283-285. 4. Kishnani PS et al J Pediatr 2006;148:671-676. 5. Kishnani PS et al. Neurology 2008 68: 99-109 [Correction appears in Neurology 2008;71:1748] 6. Chen L-R et al J Pediatr 2009;155:271-275.
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