Glycogen Storage Disease Type II: Birth Prevalence Agrees with Predicted Genotype Frequency

Abstract

Objectives: To compare the overall birth prevalence of diagnosed glycogen storage disease type II (GSD II) with the predicted frequency based on mutation screening, in order to determine whether GSD II is an underdiagnosed condition, and to analyze which medical disciplines recognize GSD II. Methods: Retrospective data on all enzymatic diagnoses of GSD II were collected from diagnostic labs throughout the Netherlands, covering the period from January 1, 1972 to December 31, 1996. Age-specific diagnostic incidence rates were calculated for the entire study period. By adding together the diagnostic incidences for all age groups, we calculated the birth prevalence of diagnosed GSD II and compared these figures with the predicted frequency based on mutation screening in a random sample from the general population. The medical specialization of the referring clinicians was also recorded. Results: GSD II was diagnosed in 154 individuals, including 11 prenatal diagnoses. The birth prevalences of the various phenotypes were 1/101,000 (infantile form), 1/720,000 (juvenile form) and 1/53,000 (adult form). The birth prevalence of the adult and infantile phenotype together was 1/35,000. Eighty-two percent of the patients were diagnosed in university hospitals. Of the patients with infantile GSD II, 71% were diagnosed by a pediatrician, whereas most patients with adult GSD II were diagnosed by a neurologist (80%). Conclusions: There is no evidence for the underdiagnosis of GSD II in the Netherlands, as the calculated birth prevalences of the disease are consistent with previous predictions based on mutation screening in a random sample of newborns. The worldwide birth prevalence of the disease may well be higher than 1 in 100,000. GSD II is mainly diagnosed in university hospitals.

Management and treatment of glycogenosis type II

“…On this basis and according to the experimental work by Ausems et al, 105 the expected frequency of carriers in the population is about 1 in 100. Glycogenosis type II is an autosomal recessive disorder, which means that affected subjects carry two mutated alleles of the GAA gene encoding for the lysosomal GAA enzyme.…”

Search for Pompe disease among patients with undetermined myopathies

“…In certain countries the reported prevalence is higher. In the Netherlands the estimated incidence of Pompe disease was calculated to be 1/40.000 based on carrier frequencies (20) and 1/35.000 based on the observed birth prevalence (21), and the in a study in New York based on carrier frequencies the estimated incidence was 1/40.000 (22). In Australia the observed incidence was reported to be 1/148.000 (23).…”

Enzymatic and molecular strategies to diagnose Pompe disease

“…These are c.525delT, c.925G> A (p.Gly309Arg), c.1655T> C (p.Leu552Pro), c.2237G> A (p.Trp746X), c.1076-1G> C (r.0?) and the deletion of exon 18 (c.2481 + 102_2646 + 31del) [64,[69][70][71][72][73][74][75][76]. All the latter mutations are severe as they are associated with classic-infantile Pompe disease in homozygous or compound heterozygous state.…”