International Pompe Association

Prof. Dr. J.J. Hopwood
Women’s and Children’s Hospital
Adelaide, Australia

Introduction

Pompe´s disease, acid maltase deficiency or glycogen storage disease type II (GSDII) is an inherited disorder of glycogen metabolism resulting from defects in the activity of the lysosomal hydrolase alpha-glucosidase and the lysosomal storage of glycogen fragments. The clinical presentation of GSDII, like all other lysosomal disorders, may present within a range of phenotypes, all of which include varying degrees of myopathy but differ with respect to age of onset and extent of organ involvement and rate of progression. The earliest onset is the classic infantile, first described by Pompe, and at the other extreme, a slowly progressive adult onset phenotype that involves only skeletal muscle.

Diagnosis

The biochemical diagnosis of GSDII is a difficult process currently involving the measurement of alpha-glucosidase activities in muscle and/or skin samples from the clinically presenting patient. Diagnosis using blood samples is complicated by the presence of other alpha-glucosidase activities. As a consequence, determination of acid alpha-glucosidase is generally not the first option with young children or adult patients presenting with muscle weakness. Infantile patients, presenting in the first few months of life with marked cardiomegaly and rapidly progressing weakness, would benefit from rapid and early diagnosis to maximise the efficacy from enzyme replacement therapies, as well as other symptomatic treatment.

A new methodology

We have been developing a new methodology to achieve fast, inexpensive and non-invasive procedures for the early detection and diagnosis of GSDII in individuals from newborns to adult populations. Immunoquantification assays were developed to separately quantify lysosomal total (mature and precursor) alpha-glucosidase and mature alpha-glucosidase. We have determined the lysosomal alpha-glucosidase protein concentration in plasma samples and Guthrie blood spots from normal controls and GSDII patients. Protein amounts in both plasma and blood samples from affected patients were generally below the control range. Tandem Mass Spectrometry methodology has been developed to determine amounts of derivatised alpha-glucosidase oligo-saccharides in blood spots from GSDII patients and control individuals.