Enzyme Replacement Therapy in Classical Infantile Pompe Disease: Results of a Ten-Month Follow-Up Study

Abstract

Infantile Pompe disease (IPD) is a fatal, autosomal recessive muscle-wasting disorder. Due to a deficiency of the lysosomal enzyme acid alpha-glucosidase patients develop a generalized myopathy, diaphragmatic weakness, and cardiomyopathy leading to death usually within the first year of life. So far there is no therapy available. We report on the safety and efficacy of transgenically derived recombinant human precursor acid alpha-glucosidase (rhGAA) in a 10-month follow-up study in two children with IPD who previously completed a 48-week course of enzyme replacement therapy (ERT) with the same medication at the same dose in a phase II clinical trial. Under this therapy cardiac status and muscle strength had improved, leading to survival beyond the age of one year. These results, together with data from two other phase II clinical trials encouraged further evaluation of the long-term safety and efficacy of enzyme replacement therapy in patients with infantile-onset Pompe disease. During the 10-month follow-up period, ERT was well-tolerated and neither patient experienced a single infusion-associated reaction. The initial improvements in cardiac size and function, as measured by left ventricular mass index and the fractional shortening, were maintained in both patients, and a continued improvement of motor function, as measured by the Alberta infant motor scale, was observed.

Pompe disease - enzyme replacement therapy - acid alpha-glucosidase

References

• 1 Amalfitano A, Bengur R, Morse R P. et al . Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial.  Genet Med. 2001;  3 132-138
• 2 Ausems M G, Verbiestm J, Hermans M P. et al . Frequency of glycogen storage disease type II in the Netherlands: implication for diagnosis and genetic counseling.  Eur J Hum Genet. 1999;  7 713-716
• 3 Braunsdorf W E. Fusiform aneurysm of basilar artery and ectatic internal carotid arteries associated with glycogenosis type 2 (Pompe's disease).  Neurosurgery. 1987;  21 748-749
• 4 Hirschhorn R, Reuser A JJ. Glycogen storage disease type II: acid α-glucosidase (acid maltase) deficiency. Scriver CR, Beaudet AL, Sly WS, Valle D (assoc. eds), Childs B, Kinzler KW, Vogelstein B The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York; McGraw-Hill 2000: 3389-3420
• 5 Kampmann C, Wiethoff C M, Wenzel A. et al . Normal values of M-mode echocardiographic measurements of more than 2000 healthy infants and children in Central Europe.  Heart. 2000;  83 667-672
• 6 Klinge L, Straub V, Neudorf U. et al . Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: Results of a phase II clinical trial.  Neuromusc Disord. 2005;  15 24-31
• 7 Makos M M, McComb R D, Hart M N, Bennet D R. Alpha glucosidase deficiency and basilar artery aneurysm: report on a sibship.  Ann Neurol. 1987;  22 629-633
• 8 Martiniuk F, Chen A, Mack A. et al . Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease.  Am J Med Genet. 1998;  345 315-319
• 9 Miyamoto Y, Etoh Y, Joh R, Kazuyoshi N, Ohya I. Adult-onset acid maltase deficiency in siblings.  Acta Pathol Jpn. 1985;  35 1533-1542
• 10 Piper M C, Darrah J. Motor Assessment of the Developing Infant. Philadelphia; WB Saunders Co 1994
• 11 Reuser A JJ, Koster J F, Hoogevee A, Galjaard H. Biochemical, immunological, and cell genetic studies in glycogenosis type II.  Am J Hum Genet. 1978;  30 132-143
• 12 Slonim A E, Bulone L, Ritz S, Goldberg T, Chen A, Martiniuk F. Identification of two subtypes of infantile acid maltase deficiency.  J Pediatr. 2000;  137 283-285
• 13 Van den Hout H, Reuser A JJ, Vulto A G, Loonen M CB, Cromme-Dljkhuis A, Van der Ploeg A T. Recombinant human α-glucosidase from rabbit milk in Pompe patients.  Lancet. 2000;  356 397-398
• 14 Van den Hout H, Reuser A JJ, de Klerk J BC, Arts W F, Smeitink J AM, Van der Ploeg A T. Enzyme therapy for Pompe disease with recombinant human α-glucosidase from rabbit milk.  J Inherit Metab Dis. 2001;  24 267-275
• 15 Van den Hout H M, Hop W, van Diggelen. et al . The natural course of infantile Pompe disease: 20 original cases compared with 133 cases from the literature.  Pediatrics. 2003;  112 332-340
• 16 Van den Hout J MP, Kamphoven J HJ, Winkel L PF. et al . Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk.  Pediatrics. 2004;  113 448-457
• 17 Vogel M, Staller W, Buhlmeyer K. Left ventricular myocardial mass determined by cross-sectional echocardiography in normal newborns, infants, and children.  Pediatr Cardiol. 1991;  12 143-149
• 18 Wenk J, Hille A, von Figura K. Quantitation of Mr 46 000 and Mr 300 000 mannose 6-phosphate receptors in human cells and tissues.  Biochem Int. 1991;  23 723-732