Third International Workshop of the Acid Maltase Deficiency Association
December 3-5, 1998 • Bethesda, MD

Thursday, December 3
11:30 a.m.	Introduction
	Acid Maltase Deficiency Randall and Marylyn House Association Office of Rare Diseases Stephen Groft Brief Overview Paul Plotz, NIH
12:00 p.m.	Keynote address
	Lysosomal Storage Diseases: Back to Biology Richard Proia, NIDDK Introduction Paul Plotz, NIH
12:30 p.m.	Buffet Lunch
1:30 p.m.	Clinical issues - Chair: Ans van der Ploeg
	Clinical overview Y. T. Chen Enzyme replacement therapy: The clinical course in children Ans van der Ploeg Treatment and followup of two cases of infantile type II glycogenosis Bruno Bembi, C. Martini, G.M. Severini, G. Ciana Identification of a subtype of infantile AMD: Severe myopathy without obstructive cardiomyopathy. Alfred Slonim, S. Spitz, F. Martiniuk, L. Bulone, T. Goldberg Clinical, histopathological, and genetic characterization of 21 patients with juvenile and adult onset acid maltase deficiency. Pascal Laforêt Respiratory concerns and practices in AMD patients J. Clarke McIntosh
	Discussion
3:00 p.m.	Bone marrow transplantation
	Gene transfer to hematopoietic stem cells John Tisdale Application of bone marrow stem cell transplantation in inherited metabolic disorders John Barrett Discussion
3:30 p.m.	Break
4:00 p.m.	Animal models - Chair: Y.T. Chen
	Modulation of disease severity in knockout mice with targeted disruption of the acid alpha-glucosidase gene Nina Raben Toward enzyme therapy: The mouse model Arnold Reuser A mouse model of Glycogen Storage Disease Type Ia Janice Chou Acid maltase deficient quail carries a single base pair deletion in exon 7 in GAA1 gene Tateki Kikuchi, O. Nakabayashi, N. Ichibara Molecular definition of bovine generalized glycogenosis Julie Dennis Discussion
5:30 p.m.	Return to hotel
7:30 p.m.	Dinner at La Miche
Friday, December 4
8:15 a.m.	Continental breakfast
9:00 a.m.	Molecular and metabolic aspects - Chair: Rochelle Hirschhorn
	A novel alpha-glucosidase that is a potential modifier of Glycogen Storage Disease Type II Rochelle Hirschhorn Transcriptional control of the human acid alpha-glucosidase gene by a silencer within intron I Bo Yan Application of basic studies of lysosomal enzyme trafficking to the treatment of Pompe disease William Canfield Enzyme replacement therapy: Production of recombinant human acid alpha-glucosidase in milk of transgenic mice and rabbits Joris Heus Purification and characterization of recombinant human acid alpha-glucosidase from transgenic rabbit milk Emile van Corven Discussion
10:30 a.m.	Break
11:00 p.m.	Gene therapy I - Chair: Fabio Candotti
	Gene therapy: Where we've been and where we're going R. Michael Blaese, NHGRI A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder Richard Proia Bone marrow transplantation in Sandhoff disease: Implications for therapy and pathogenesis Cynthia Tifft Helious gene gun delivery for gene therapy of acid maltase deficiency Frank Martiniuk
12:15 p.m.	Lunch
1:15 p.m.	Gene therapy II - Chairs: Barry Byrne and Paul Kessler
	Acid maltase deficiency: Studies with AAV vectors Barry Byrne Acid maltase deficiency: studies with adenovirus vectors Paul Kessler Widespread reversal of glycogen accumulation in the AAG-knockout mouse after AD vector delivery of the AAG cDNA to the liver Andy Amalfitano An approach to gene therapy using an adeno-associated virus vector in fibroblasts, myoblasts, and myocytes from patients with Pompe's disease C. Y. Lin In vitro and in vivo study of adenovirus-mediated gene therapy of acid maltase deficiency Discussion Seiichi Tsujino
3:15 p.m.	Break
3:45 p.m.	Human trials - Chair: Arnold Reuser
	Gaucher experience Towards enzyme therapy for patients with type 2 (Acute Neuronopathic) Gaucher Disease Roscoe Brady Genetic and environmental factors in the pathogenesis of Gaucher Disease Edward Ginns GSDII Toward enzyme therapy of acid maltase deficiency: A phase II clinical trial Ans van der Ploeg Discussion
6:00 p.m.	Return to hotel
Evening	Free
Saturday, December 5
8:15 a.m.	Continental breakfast
9:00 a.m.	Mutations and population studies - Chairs: Nina Raben and Paul Plotz
	Overview Nina Raben Increased occurrence of cleft lip in Glycogen Storage Disease Type II: Exclusion of a contiguous gene syndrome in two patients Rochelle Hirschhorn Molecular characterization of alpha-glucosidase deficiency in 40 French patients Mark Nicolino, L. Poenaru Acid Maltase Deficiency: Genotype-phenotype correlation in Italian patients Serenella Servidei, A. Spinazzola, M. Mirabella, G. de Rosa, S. DiGiovanni, P. Tonali A large (9 kb) Alu-mediated deletion extending past the 3' end of the gene in Glycogen Storage Disease Type II Rochelle Hirschhorn Unusual features of acid maltase deficiency Moris Danon Discussion
11:00 a.m.	Break
11:30 a.m.	Toward enzyme therapy: the role of a data base Hannerieke van der Hout Translating science into English: The role of patient organizations and the Internet in helping patients to become intelligent customers Kevin O'Donnell The Acid Maltase Deficiency Association registry Discussion Randall and Marylyn House
12:30 p.m.	Lunch
1:30 p.m.	End of workshop

The Third International Workshop of the Acid Maltase Deficiency Association was held at the Cloister on the NIH campus in Bethesda in December 1998. Like the previous workshops, which had been organized by Randall and Marylyn House, founders of the AMDA, this workshop aimed to bring together everyone in the world working on or with a major interest in this severe inherited disease. The workshop was held on the Bethesda campus in order to draw in scientists working at NIH on related diseases and to thereby stimulate new ideas.

The attendance was outstanding, with participants from all the groups in the world, and about a dozen scientists from six different NIH institutes (NHLBI, NIDDK, NIMH, NCHGR (presently named NHGRI), NINDS, and NICHD) lectured on related topics and contributed to discussions. The discussions and lectures ranged over mechanisms of disease, animal models, new therapies, population studies, and patient concerns. The emphasis was on therapies - particularly enzyme replacement therapy for which trials were about to begin, and gene therapy, which is being actively pursued by several groups with promising results in animals.

Because the meeting was a workshop, meant to foster open discussion and new ideas rather than to achieve a specific goal, it is hard to point to conclusive results. However, a number of new research alliances were forged. For example, discussions concerning the detailed structure of recombinant enzymes have led to new collaboration between carbohydrate chemists and molecular biologists. At the next workshop the early results of clinical trials will be discussed.

Paul Plotz, M.D. Chief, ARB, NIAMS