Genotype‐phenotype correlation in adult‐onset acid maltase deficiency

Abstract

We performed a clinical, biochemical, and genetic study in 16 patients from 11 families with adult-onset acid maltase deficiency. All patients were compound heterozygotes and carried the IVS1(-13T --> G) transversion on one allele; the second allele harbored either a deletion of a T at position 525 in exon 2 (7 probands, 64%) or a deletion of exon 18 (1 proband, 9%). Deterioration of handicap was related to age, and decrease in vital capacity to duration of the symptomatic stage. Respiratory insufficiency was never the first manifestation. The levels of activity of serum creatine kinase and of alpha-glucosidase in peripheral blood cells or muscle were helpful for the diagnosis, but did not have prognostic value. The adult form of acid maltase deficiency appears to be both clinically and genetically rather homogeneous; decrease of alpha-glucosidase activity is the final common pathway leading to destruction of muscle fibers and progression of muscle weakness over a period of years.

Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease

“…Disease severity was not related to age. Retrospective data indicated a gradual decline in respiratory and locomotor function over time, as previously described by WOKKE et al [26]. Interestingly, noninvasive MV initiation or tracheostomy did not seem to be associated with an abrupt deterioration in respiratory muscle function, in contradiction with the results of a review on the effects of MV [27].…”

The cost-effectiveness of enzyme replacement therapy (ERT) for the infantile form of Pompe disease: comparing a high-income country's approach (England) to that of a middle-income one (Colombia)

“…Survival rates during the first year of life would be expected to improve from 8 % without treatment to 40 % and even closer to 100 % with ERT; decreased cardiac hypertrophy, major milestones regarding motor development and later progression of respiratory insufficiency could increase life expectancy at birth for this population by up to at least 20 years according to experts' opinion (1)(2)(3)8,9).…”

Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling

“…3,4 The figure of 1 in 100 000 normally quoted is not based on solid data. 1,5 Given present knowledge of the molecular genetics of GSD II, 1,2,6 and the genotype-phenotype correlation, 7,8 we now have the tools to update the meagre and aging data on the frequency of the disease. In order to determine the frequency of GSD II we screened a random sample of newborns for three frequent mutations in the acid α-glucosidase gene.…”

“…In order to determine the frequency of GSD II we screened a random sample of newborns for three frequent mutations in the acid α-glucosidase gene. These mutations are IVS1(-13T→G), leading to late-onset GSD II, 7,9,10 and two completely deleterious mutations 525delT and ) a adult GSD II q m : allele frequency of the mild IVS1(-13T→G) mutation q st : allele frequency of the two severe mutations tested (525delT and delexon18) q se : extrapolated allele frequency of severe mutations q e : extrapolated allele frequency of all GSD II mutations (eg the mild IVS1(-13T→G) mutation and all severe mutations) a predicted frequency of homozygosity for the IVS1 (-13T→G) mutation (q m 2 ) is not included because this genotype probably does not give rise to clinical symptoms 9,10,16 . delexon18. [11][12][13][14] In total these mutations comprise 63% of the disease-related alleles in the Dutch patient population.…”