Pregnancy Outcomes in Late Onset Pompe Disease

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2–0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

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Pregnancy Outcomes in Late Onset Pompe Disease and Enzyme Replacement Therapy

10.20944/preprints202007.0611.v1 ◽

2020 ◽

Author(s):

Ozlem Goker-Alpan ◽

Vellore G. Kasturi ◽

Maninder K. Sohi ◽

Renuka P. Limgala ◽

Stephanie L. Austin ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pregnancy Outcomes ◽

Pompe Disease ◽

Late Onset ◽

Small Sample Size ◽

Respiratory Muscles ◽

Small Sample ◽

Enzyme Replacement ◽

Initial Symptoms

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

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Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

International Journal of Molecular Sciences ◽

10.3390/ijms22073625 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3625

Author(s):

Filomena Napolitano ◽

Giorgia Bruno ◽

Chiara Terracciano ◽

Giuseppina Franzese ◽

Nicole Piera Palomba ◽

...

Keyword(s):

Pompe Disease ◽

Rare Variants ◽

Clinical Symptoms ◽

Late Onset ◽

Respiratory Muscles ◽

Autosomal Recessive Disorder ◽

Compound Heterozygous ◽

Enzyme Replacement ◽

Whole Exome ◽

Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

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Clinical efficacy of the enzyme replacement therapy in patients with late-onset Pompe disease: a systematic review and a meta-analysis

Journal of Neurology ◽

10.1007/s00415-021-10526-5 ◽

2021 ◽

Author(s):

Berli Sarah ◽

Brandi Giovanna ◽

Keller Emanuela ◽

Najia Nadi ◽

Vitale Josè ◽

...

Keyword(s):

Muscle Strength ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Meta Analysis ◽

Small Sample ◽

Walking Distance ◽

Enzyme Replacement ◽

Muscle Testing

AbstractIn patients with late-onset Pompe disease (LOPD), the efficacy of the enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) is difficult to evaluate, due to the clinical heterogeneity and the small sample sizes in published studies. Therefore, we conduct a systematic literature review and meta-analysis of the literature to evaluate the efficacy of ERT in LOPD patients considering the walking distance, respiratory function and muscle strength. Particularly, six-minute walk test (6MWT), forced vital capacity (FVC), medical research council (MRC) grading, quantitative muscle testing (QMT), and quick motor function test (QMFT) were outcomes of interest. Overall, 619 studies were identified in PubMed, EMBASE and by manual search on July 18th, 2020. After an initial assessment, 16 studies were included in the meta-analysis, containing clinical data from 589 patients with LOPD. For the 6MWT, 419 patients were analyzed. Walking distance improved on average, 32.2 m greater during the observed period (p = 0.0003), compared to the distance at the baseline. The meta-analysis did not show any improvement in FVC and only a tendency towards better muscle strength after treatment with ERT, but the difference was not statistically significant. In conclusion, the available data showed that ERT has a significant beneficial efficacy in the improvement of walking distance in LOPD patients and a non-significant improvement of muscle strength. No improvement in respiratory capacity was found. More prospective and controlled trials are needed to demonstrate a clear clinical benefit of ERT.

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Multicenter Targeted Population Screening of Late Onset Pompe Disease in Unspecified Myopathy Patients in Korea

Journal of the Korean Neurological Association ◽

10.17340/jkna.2021.2.3 ◽

2021 ◽

Vol 39 (2) ◽

pp. 75-81

Author(s):

Jung Hwan Lee ◽

Jin-Hong Shin ◽

Dae-Seong Kim ◽

Kwang-Kuk Kim ◽

Byoung Joon Kim ◽

...

Keyword(s):

Pompe Disease ◽

Autosomal Recessive ◽

Late Onset ◽

Asian Population ◽

Autosomal Recessive Disorder ◽

Enzyme Replacement ◽

The Mean ◽

Pseudodeficiency Allele ◽

Alpha Glucosidase ◽

Positive Results

Background: Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea.Methods: From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of <i>GAA</i> gene.Results: Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele.Conclusions: This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

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Delivery and postpartum management of a patient with Pompe disease: Case report and review of the literature

Obstetric Medicine ◽

10.1177/1753495x16688601 ◽

2017 ◽

Vol 10 (3) ◽

pp. 150-151 ◽

Cited By ~ 1

Author(s):

Kazibe Koyuncu ◽

Batuhan Turgay ◽

Rusen Aytac ◽

Feride Soylemez

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Autosomal Recessive ◽

Late Onset ◽

Autosomal Recessive Disorder ◽

Enzyme Replacement ◽

Disease Case ◽

Alpha Glucosidase ◽

Gaa Gene

Pompe disease is an autosomal-recessive disorder caused by acid alpha-glucosidase deficiency due to mutations in the GAA gene. There are two forms of the disease: infantile-onset Pompe disease and late-onset Pompe disease. The worldwide incidence of both forms of the disease is commonly reported to be 1 in 40,000. Adult patients are affected by limb-girdle muscular weakness and respiratory insufficiency. Enzyme replacement therapy with alglucosidase-alpha is available since 2006. There is little knowledge about pregnant woman with Pompe disease. These women should be considered as high-risk pregnant women. Here, we aim to present Cesarean delivery and postpartum management of a case with an interrupted enzyme replacement therapy during pregnancy.

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Respiratory manifestations in late-onset Pompe disease: a case series conducted in Brazil

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562015000000343 ◽

2017 ◽

Vol 43 (1) ◽

pp. 54-59 ◽

Cited By ~ 2

Author(s):

Bruna de Souza Sixel ◽

Luanda Dias da Silva ◽

Nicolette Celani Cavalcanti ◽

Glória Maria Cardoso de Andrade Penque ◽

Sandra Lisboa ◽

...

Keyword(s):

Symptom Onset ◽

Pompe Disease ◽

Late Onset ◽

Case Series ◽

Definitive Diagnosis ◽

Walk Distance ◽

Enzyme Replacement ◽

Initial Symptoms ◽

Minute Walk Distance ◽

Minute Walk

ABSTRACT Objective: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy. Methods: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability. Analyses were carried out using frequencies, medians, minimum values, and maximum values. Results: Six patients were included in the study. The median age at symptom onset was 15 years (range, 13-50 years), and the median age at diagnosis was 39.5 years (range, 10-64 years). The median time from symptom onset to diagnosis was 8 years (range, 0-45 years). In all cases, the initial manifestation of the disease had been motor weakness. The median FVC in percentage of the predicted value (FVC%) in the sitting and supine positions was 71.0% (range, 22.9-104.6%) and 58.0% (range, 10.9-106.9%), respectively. The median ΔFVC% was 24.5% (range, −4.59 to 52.40%).The median six-minute walk distance was 391.7 m (range, 97-702 m) . Conclusions: In this case series, the time from symptom onset to diagnosis was long. Although respiratory signs or symptoms were not the initial manifestations of the disease, 66.7% of the patients showed reduced FVC% in the sitting and supine positions at diagnosis.

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Late-onset Pompe disease: preliminary results of enzyme replacement therapy

Neuromuscular Diseases ◽

10.17650/2222-8721-2019-9-2-43-49 ◽

2019 ◽

Vol 9 (2) ◽

pp. 43-49

Author(s):

L. P. Smertina ◽

F. I. Ausheva ◽

A. V. Gryaznov ◽

D. A. Svetlakov ◽

L. N. Kolbasin

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Respiratory Muscles ◽

Preliminary Results ◽

Enzyme Replacement ◽

Acid Maltase ◽

Body Tissues ◽

Before And After

Pompe disease is an orphan hereditary accumulation disease associated with a deficiency of the lysosomal enzyme alglucosidase alpha. Manifestations of the disease are associated with pathological deposition of glycogen in body tissues as a result of GAA gene mutation and subsequent reduction in the activity of the enzyme alglucosidase alpha or acid maltase. The variety of phenotypic forms and varying degrees of damage to the skeletal and respiratory muscles, cardiomyocytes and internal organs greatly complicates the diagnosis and treatment of patients with Pompe»s disease. This article describes the clinical case of late-onset Pompe disease, which was followed by a course of enzyme replacement therapy, as well as an assessment of the condition before and after treatment and preliminary results.

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