Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pompe disease”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

[Glycogen storage disease (Pompe's disease) presenting as myopathy in the adult (author's transl)].

In a 46-year-old woman with progressive atypical limb-girdle dystrophy for eight years the electromyogram revealed a myopathic pattern with signs of denervation activity. Enzymehistochemical and biochemical investigations of muscle and liver biopsies indicated type II glycogen storage disease (Pompe's disease). This type, with its prolonged course and the almost exclusive clinical involvement of proximal muscles mimics a "degenerative" neuromuscular disease, particularly muscle dystrophy, in the adult. Caused by acid maltase deficiency it is not a rare disease.

Age Factors↗
PubMed2025

Reduction of false-positive results with biochemical second-tier testing for newborn screening of Pompe disease.

PURPOSE: To review the performance and outcomes of a second-tier newborn screening test for Pompe disease. METHODS: We followed our previously published screening approach that reduces false-positive results by incorporating creatine and creatinine levels and postanalytic tools in a second-tier test. RESULTS: We reviewed 1879 blood samples from neonates born in 11 states. Second-tier testing effectively reduced false-positive results, compared with first-tier enzyme testing alone. Only a small number of screen-positive cases (n = 7) were confirmed to have infantile-onset Pompe disease. No false-negative cases of infantile-onset Pompe disease were identified in this cohort, and 6 cases of possible late-onset Pompe disease were not detected with this approach. CONCLUSION: This tiered screening strategy discriminated well between true- and false-positive results and improved the positive predictive value. However, it did not reliably differentiate between infantile- and late-onset Pompe disease.

Humans↗
PubMed2026

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid &#x3b1;-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient &#x2264;66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score &#x2265;7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article↗
PubMed1977

Creatine kinase and lactate dehydrogenase in type 2 glycogenosis (Pompe disease).

At least three varieties of type 2 glycogenosis (Pompe disease) have been described, the most severe of which is an infantile form. The relationship between clinical manifestations, glycogen accumulation, and tissue damage has not been established. Serum levels of creatine kinase (CK [EC 2.7.3.2 adenosine triphosphate:creatine phosphotransferase]) lactate dehydrogenase (LDH [EC 1.1.1.27 L-lactate:NAD oxidoreductase]) and their isoenzyme fractions were used to identify and monitor myocardial damage in this study of an infant with type 2 glycogenosis diagnosed by light microscopy and tissue enzyme assay.

Creatine Kinase↗
PubMed1978

Searching for molecular abnormalities in genetic diseases by the use of a double labeling technique. II. Deficiency of a basic protein in fibroblasts of patients with Pompe's disease.

We used a double labeling technique to search for molecular defects in two fibroblast strains obtained from patients with Pompe's disease. Analysis of the double labeled subcellular fractions by sodium dodecyl sulfate (SDS) electrophoresis did not reveal any abnormalities except in the "mitochondrial-lysosomal" fraction. In this fraction ratio deviations indicated that in Pompe's disease there was a significant decrease in counts of a protein with molecular weight of about 29,000. After solubilization by freeze-thawing this protein was shown to have an isoelectric point of 7.9 in contrast to the alpha-glucosidase which focused at about pH 4.7. Two-stage gel studies demonstrated an estimated 90% reduction of this protein in Pompe's disease. Two-stage studies of acid alpha-glucosidase did not show any abnormal ratios of leucine incorporation. Similar although quantitatively less pronounced results were obtained in the study of skin fibroblasts from a patient with adult glycogen storage disease type II.

Adult↗
PubMed1978

A sensitive semi-automated kinetic assay of alpha-D-glucosidase for the prenatal diagnosis of type 2 glycogenosis (Pompe's disease).

Prenatal diagnosis of type 2 glycogenosis (Pompe's disease) has been done on cultured amniotic fluid cells, using a semi-automated fluorimetric kinetic assay for alpha-D-glucosidase with 4-methylumbelliferyl-alpha-D-glucoside as substrate. The activity of the enzyme was related to that of beta-D-galactosidase, and found to be absent in cells from an affected fetus. The diagnosis was confirmed in fetal liver, where the same assay was used to show absence of alpha-D-glucosidase activity with normal beta-D-galactosidase activity, and where increased glycogen deposition was demonstrated histologically. This type of assay is generally applicable to lysosomal enzymes, and to other fluorigenic enzyme reactions.

Amniocentesis↗
PubMed1976

Echocardiographic evidence of outflow tract obstruction in Pompe's disease (glycogen storage disease of the heart).

A 7 month old black female infant with the clinical findings of Pompe's disease is presented. The diagnosis of an infiltrative myocardiopathy with left ventricular outflow tract obstruction presenting with a pronounced systolic anterior motion of the anterior mitral valve leaflet was made by echocardiography. This diagnosis was confirmed by cardiac catheterization and angiocardiography. Pathologic findings were consistent with Pompe's disease (type II glycogen storage disease). The presence of systolic anterior motion of the mitral valve in this patient suggests that this finding is not pathognomonic of idiopathic hypertrophic subaortic stenosis.

Angiocardiography↗
PubMed1979

Use of immobilized antibodies in investigating acid alpha-glucosidase in urine in relation to Pompe's disease.

(1) A simple method is described for the isolation of the lysosomal enzyme, acid alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20) from normal human liver. Antibodies raised against the purified enzyme were immobilized by covalent coupling to Sepharose 4B. (2) Acid alpha-glucosidase can be quantitatively removed from normal urine by incubating with an excess of immobilized antibody. With p-nitrophenyl-alpha-glucoside as substrate, acid alpha-glucosidase accounts for 91 +/- 3% of the total alpha-glucosidase activity at pH 4.0 IN Normal urine. (3) In urine from a patient with the infantile form of Pompe's disease ('acid maltase deficiency'), no alpha-glucosidase activity could be removed by the immobilized antibody, in agreement with the fact that acid alpha-glucosidase is absent in these patients. (4) In urine from patients with the late-onset form of Pompe's disease, 46 +/- 11% of the alpha-glucosidase activity at pH 4.0 can be removed by incubation with immobilized antibodies, indicating that residual acid alpha-glucosidase activity is present in urine of these patients. The residual acid alpha-glucosidase activity amounts to about 5% of that in the urine of control persons. (5) If acid alpha-glucosidase is adsorbed to immobilized antibodies, the activity can still be measured with p-nitrophenyl-alpha-glucoside as substrate. The Km for p-nitrophenyl-alpha-glucoside is not significantly changed by adsorbing purified acid alpha-glucosidase to immobilized antibodies. (6) The properties of acid alpha-glucosidase from urine of patients with late-onset Pompe's disease were compared with those of acid alpha-glucosidase from normal urine, both adsorbed to immobilized antiserum. The pH-activity profile of the enzyme from urine of patients with late-onset Pompe's disease can not be distinguished from that of the normal urinary enzyme. The Km for p-nitro-phenyl-alpha-glucoside of the two enzymes is identical, both at pH 4 and 3. The titration curves of the two enzymes with immobilized antibodies are identical.

Glucosidases↗
PubMed1978

The change in the pH 4 and pH 6 forms of alpha-glucosidase in cultured amniotic fluid cells and its implication in prenatal diagnosis of Pompe's disease.

Activities of two major forms of alpha-glucosidase in cultured amniotic fluid cells have been measured by the 4-methylumbelliferyl-alpha-D-glucoside assay after 3, 6 and 9 weeks of culturing. Activity of the pH 4 forms of alpha-glucosidase, which is deficient in Pompe's disease, was low in early culture but increased rapidly as the culture time was increased. The cells harvested at 3 weeks had a low absolute activity of the pH 4 form as well as low ratio of the pH 4 to pH 6 enzyme. The pH 6 form is not affected in Pompe's disease. The results suggest cautions when attempting early diagnosis by use of microtechniques and re-emphasizes the need for differentiation of these two forms of alpha-glucosidases in prenatal diagnosis of Pompe's disease.

Amniotic Fluid↗
PubMed1977

A micro-radiochemical assay for alpha-1,4-glucosidase and its use in the assessment of type II glycogenosis (Pompe's disease).

An assay for alpha-1,4-glucosidase (acid maltase) activity which is deficient in Pompe's disease is described. The assay can be used to measure the enzyme in cultured skin fibroblasts, cultured amniotic cells and peripheral blood leucocytes. [U-14 C]Maltose is used as the substrate in a total assay volume of 8 microliter. The product, [U-14C]glucose, is separated from the substrate by cellulose thin-layer chromatography. The procedure permits replicate assays from 400 microliter whole blood and from amniotic cells in primary culture. Discrimination of the heterozygous Pompe state appears to be facilitated.

Amnion↗
PubMed1978

Pompe's disease: ultrastructural alterations of muscle tissue in parents.

A histological, histochemical and ultrastructural study of muscle tissue was performed in the parents of a patient affected by a infantile form of acid maltase deficiency (Pompe's disease). In both parents the clinical examination was normal, but serum levels of creatine kinase (CK) and aldolase were high. Histological and histochemical examination of muscle did not reveal any abnormality. Ultrastructural study showed an excess of glycogen granules below the sarcolemmal sheat and between myofibrils, often associated with clusters of mitochondria. There was no glycogen trapped in lysosomal vesicles. The mechanism of glycogen storage in Pompe's disease seems to involve an enzymatic deficiency other than acid maltase.

Adult↗
PubMed1978

Pompe's disease: diagnosis in kidney and leucocytes using 4-methylumbelliferyl-alpha-D-glucopyranoside.

The diagnosis of Pompe's disease by the assay of acid alpha-glucosidase in kidney and leucocytes was not previously possible because of the presence of another component which had activity at pH 4.0, but was not deficient in the disease. This problem was resolved either by the use of the inhibitors, turanose, maltose and citrate, or by isoelectric precipitation at pH 5.0, which enabled the estimation of acid alpha glucosidase in kidney and leucocytes.

Glucosides↗
PubMed1977

Urinary alpha-glucosidase analysis for the detection of the adult form of Pompe's disease.

Two alpha-glucosidases from human heart, liver, muscle, kidney and urine have been separated by means of Sephadex G-100 gel filtration. The first peak (Peak I) was neutral alpha-glucosidase and the second peak (Peak II) was lysosomal acid alpha-glucosidase. Peak II was absent in a patient with the adult form of Pompe's disease. KCl stimulated the activity of the Peak II enzyme but it strongly inhibited the activity of the Peak I enzyme measured at pH 4.0. Decreases in the urinary alpha-glucosidase activity measured at pH 4.0 with added KCl and the ratio of the activity at pH 4.0 with added KCl/the activity at pH 6.5 without KCl may aid in the detection of homozygotes or heterozygotes with the adult form of Pompe's disease.

Adolescent↗
PubMed1976

Two alpha-glucosidases in cultured amniotic fluid cells and their differentiation in the prenatal diagnosis of Pompe's disease.

A sensitive fluorometric assay utilizing 4-methylumbelliferyl-alpha-D-glucopyranoside has been developed for the determination of alpha-glucosidase. The enhanced sensitivity was achieved by increasing the solubility of the substrate with a water miscible organic solvent. With this system, cultured amniotic fluid cells were found to have two major forms of alpha-glucosidase with somewhat overlapping acidic pH optima; one with pH optimum at 4.5 is deficient in Pompe's disease (type II glycogenosis), while one with pH optimum at 6.0 is not affected in this disease. Specificity for the pH 4 form of alpha-glucosidase was achieved by exploiting the greater thermal lability of the pH 6 enzyme. The pH 6 form of the enzyme was also detectable in freshly prepared extracts of cultured fibroblasts. The procedure is direct and simple and has been applied to the prenatal diagnosis in two pregnancies at risk for Pompe's disease.

Amniotic Fluid↗
PubMed1977

Properties of the alpha-glucosidase from various human tissues in relation to glycogenosis type II (Pompe's disease).

The physico-chemical and electrophoretical properties of alpha-glucosidases from various human tissues and urine have been studied. There were some differences among Peak I enzymes (neutral alpha-glucosidases) obtained from liver, heart, muscle, kidney and urine. These differences are based on different effects of tris(hydroxymethyl)aminomethane and various thermostabilities of the Peak I enzymes. Electrophoretically, the Peak I enzyme activity at pH 6.5 from control tissues displayed a two-banded pattern except in kidney and urine. In the patient with the adult form of Pompe's disease the faster band of the Peak I enzyme from heart and muscle was not found and the slower band of the Peak I enzyme from liver was more cathodic. The results are discussed in relation to glycogenosis type II (Pompe's disease).

Copper↗
PubMed1978

alpha-Glucosidase in Pompe's disease.

Isoelectric precipitation at pH 5.0 and the use of the inhibitors, turanose, maltose and citrate, enabled the diagnosis of Pompe's disease to be made in dextran-isolated leucocytes using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate. These techniques were unnecessary with lymphocytes as the deficiency of acid alpha-glucosidase could be shown directly.

Clinical Enzyme Tests↗