Progressive Proximal Muscle Weakness Research Articles

A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G\u2009>\u2009C; p.Gly12Ala point mutation

BackgroundOculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy characterised by slowly progressive ptosis, dysphagia, and proximal limb muscle weakness. A common cause of OPMD is the short expansion of a GCG or GCA trinucleotide repeat in PABPN1 gene.Case presentationA 78-year-old woman presented with ptosis and gradually progressive dysphagia. Her son had the same symptoms. A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. Needle-electromyography (EMG) of bulbar and facial muscles revealed a myopathic pattern. Based on the characteristic muscle involvement pattern and needle-EMG findings, we suspected that the patient had OPMD. Gene analysis revealed PABPN1 c.35G > C point mutation, which mimicked the effect of a common causative repeat expansion mutation of OPMD.ConclusionWe herein describe the first reported Japanese case of OPMD with PABPN1 point mutation, suggesting that this mutation is causative in Asians as well as in Europeans, in whom it was originally reported.

A case of dermatomyositis in a patient with central core disease: unusual association with autoimmunity and genetic muscle disease

BackgroundDermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy.Case presentationHere, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patient’s muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength.ConclusionsWe present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.

Acute polymyositis presenting as chronic graft-versus-host disease: A systemic review.

e19025 Background: Chronic graft-versus-host disease (cGvHD) remains a significant complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), with an estimated incidence of over 50%. Commonly targeted organs are skin, eyes, mouth, gastrointestinal tract, and liver. Muscular involvement and presentation as acute polymyositis (APM) remains a rare manifestation of cGvHD. We present a systemic review of APM associated with cGvHD to summarize current evidence regarding epidemiology, clinical presentation, diagnosis, treatment, and prognosis. Methods: A systemic review was conducting following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We screened 97 articles from 3 databases (PubMed, Embase, and Cochrane) using the MeSH terms and keywords for “Allogenic stem cell transplantation,” “Chronic graft-versus-host disease,” “Polymyositis” and “Myositis” from the date of inception to Jan 2021. After excluding duplicate, review and non-relevant articles, we included 36 studies (3 retrospective, others case series/reports) reporting APM associated with cGvHD after allo-HSCT. Results: We identified 72 patients, presented with APM associated with cGvHD after allo-HSCT. It involves cases of all ages, with male predominance. The onset of APM ranges as early as 100 days to 5 years, with a median range of 1.6 years post-allo-HSCT. Over half (59%) of patients had prior acute GvHD. Majority (85%) of cases presented with myalgia and progressive bilateral proximal muscle weakness with elevated Creatine phosphokinase (CPK) and/or Aldolase. Isolated presentation of APM without other manifestations of GvHD was rare, and concurrent skin involvement was present in 42% cases. Steroids remain the mainstay of treatment, achieving complete treatment response in up to 78% of cases. In some refractory cases, Rituximab has also been effective. Conclusions: APM can present as a sole manifestation of cGvHD with an estimated incidence of up to 3.4%. Diagnosis can be challenging as it can mimic idiopathic polymyositis. Radiologically targeted muscle biopsy showing characteristic myonecrosis remains the gold standard for diagnosis. Most (90%) cases respond to steroids and immunosuppression agents. Nevertheless, refractory cases remain challenging to treat and can cause significant morbidity and mortality. Characteristics of APM in 3 cohorts of allo-HSCT patients.[Table: see text]

OP0008 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE III TRIAL OF IVIG 10% IN PATIENTS WITH DERMATOMYOSITIS. THE PRODERM STUDY: RESULTS ON EFFICACY AND SAFETY

Background:Dermatomyositis (DM) is a rare chronic systemic autoimmune disease with characteristic skin rash and progressive proximal muscle weakness. Current therapies encompass corticosteroids and other immunosuppressants and intravenous immunoglobulins (IVIg), however, none of these therapies are proven by randomized controlled phase 3 studies. There have been no large randomized clinical trials supporting the efficacy and safety of IVIg in DM.Objectives:The ProDERM study aimed to evaluate the efficacy and safety/tolerability of IVIg in DM patients in a double-blind, randomized, placebo-controlled, international multi-center, phase III clinical trial.Methods:The trial consisted of a double-blind, placebo-controlled First Period (16 weeks), in which adult patients with definite or probable DM (according to Bohan and Peter criteria) were randomized 1:1 to either high dose IVIg (2g/kg every 4 weeks) or placebo. Patients on placebo and patients without clinical worsening while on IVIg treatment entered the open label Extension Period (24 weeks) and received 2g/kg IVIg infusions every 4 weeks. To be included, subjects must have active disease with a manual muscle testing-8 (MMT-8) score < 142/150. Patients who showed clinical worsening (defined according to Oddis et al, 2013 - with slight adaptation) at 2 consecutive visits between week 8 and week 16 were switched to the alternate treatment arm.Primary endpoint was the proportion of responders in the IVIg vs. placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis response criteria of at least minimal improvement [Total Improvement Score (TIS) ≥ 20 points)] and without clinical worsening at 2 consecutive visits up to week 16.Results:A total of 95 adult DM patients (mean age: 53 years; 75% females; 92% Caucasian) were enrolled, with 47 and 48 randomized to IVIg and placebo, respectively. Baseline clinical characteristics (including medical history and prior DM medication) were balanced between the 2 arms.The study met the primary endpoint at week 16, with the proportion of responders being significantly higher in the IVIg group (37/47; 78.7%) as compared to the placebo group (21/48; 43.8%; p-value 0.0008; Table 1).Table 1.Total Improvement Score – Analysis of Proportion of Responders at Week 16 (Full Analysis Set, N=95)TIS Responseoctagam 10%N=47PlaceboN=48Difference octagam 10% – placeboNumber (%) of responders37 (78.72%)21 (43.75%)Difference in response rates34.97[95% CI] p-valuea[16.70, 53.24] 0.0008aCochran-Mantel-Haenszel TestCI=confidence interval; N=number of patients; TIS=total improvement scoreIn the analysis of responders per improvement category at Week 16, a 45.2% higher response rate for at least moderate improvement (TIS ≥n40 points; p < 0.0001) and a 23.6% higher response rate for at least major improvement (TIS ≥060 points; p < 0.0062) was observed in the IVIG group as compared to the placebo group.The mean (SD) TIS was significantly higher in IVIg group [48.4 (24.4)] than in placebo arm [21.6 (20.2)] at week 16 (Fig 1).Figure 1.After switching to IVIG in the Extension Period the placebo group attained a similar response rate at Week 40 as did the IVIg treated patients at Week 16, i.e approx. 70% for minimal improvement.In line with the overall primary endpoint, secondary end points including all of the sub-components of TIS except muscle enzyme (MMT-8, MD global, Extramuscular global, patient global, HAQ,) as well as CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index), also showed statistically significant improvement under IVIg treatment compared to placebo treatment.The safety and tolerability profile of IVIg was consistent with previously reported safety outcomes for IVIg administration.Conclusion:This is the first large international phase III randomized, placebo-controlled trial demonstrating the efficacy and safety of IVIg as a treatment for patients with DM.

Comparison of The Carrier Frequency of Pathogenic Variants of DMD Gene in an Indian Cohort.

Duchenne muscular dystrophy (DMD) is an X-linked disorder caused due to large deletions, duplications,and small pathogenic variants. This article compares the carrier frequency of different pathogenic variants in the DMD gene for the first time in an Indian cohort. Ninety-one mothers of genetically confirmed DMD probands are included in this study. Pathogenic variants in the DMD gene in probands were detected by multiplex ligation-dependent probe amplification (MLPA) or next-generation sequencing (NGS). Maternal blood samples were evaluated either by MLPA or Sanger sequencing. The demographic and clinical details for screening of muscle weakness and cardiomyopathy were collected from the confirmed carriers. Out of 91 probands, large deletions and duplications were identified in 46 and 6 respectively, while 39 had small variants. Among the small variants, substitutions predicted to cause nonsense mutations were the most common (61.5%), followed by frameshift causing small insertion/deletions (25.6%) and splice affecting intronic variants (12.8%). Notably, 19 novel small variants predicted to be disease-causing were identified. Of the 91 mothers, 53 (58.7%) were confirmed to be carriers. Exonic deletions had a significantly lower carrier frequency of 47.8% as compared to small variants (64.1%). The mean age of the carriers at evaluation was 30 years. Among the carriers, two were symptomatic with onset in the 4th decade, manifesting with progressive proximal muscle weakness and dilated cardiomyopathy. Carrier frequency of small pathogenic variants differs significantly from large deletions. Small pathogenic variants are more commonly inherited, whereas large deletions arise de novo.

A Patient With Late-onset Limb-girdle Muscular Dystrophy Type 2B Mimicking Dermatomyositis: A Case Report and Review.

Limb-Girdle Muscular Dystrophy 2B (LGMD2B) presents with proximal and/or distal muscle weakness and markedly high creatine kinase level. It is caused by the loss of dysferlin due to mutations in the DYSF gene. Due to its similar clinical features as inflammatory myopathy, it is often difficult to distinguish between the two. We present a case of a 48-year-old male who developed progressive proximal muscle weakness, papulosquamous lesions on the knuckles, elevated levels of muscle enzymes, and electromyogram abnormalities. Based on the clinical presentation, the initial impression was dermatomyositis, yet it was refractory to immunosuppressive therapy. Subsequently, dysferlin immunostaining and genetic analysis led to the final diagnosis of LGMD2B. This case shows that LGMD2B can present with extramuscular symptoms mimicking inflammatory myopathy in later stages of life. Dysferlin immunostaining and/or genetic analysis of the DYSF gene are essential for its diagnosis.

Muscle Proteomic Profile before and after Enzyme Replacement Therapy in Late-Onset Pompe Disease

Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the efficacy of ERT is variable. Here we address the question whether proteins at variance in LOPD muscle of patients before and after 1 year of ERT, compared withhealthy age-matched subjects (CTR), reveal a specific signature. Proteins extracted from skeletal muscle of LOPD patients and CTR were analyzed by combining gel based (two-dimensional difference gel electrophoresis) and label-free (liquid chromatography-mass spectrometry) proteomic approaches, and ingenuity pathway analysis. Upstream regulators targeting autophagy and lysosomal tethering were assessed by immunoblotting. 178 proteins were changed in abundance in LOPD patients, 47 of them recovered normal level after ERT. Defects in oxidative metabolism, muscle contractile protein regulation, cytoskeletal rearrangement, and membrane reorganization persisted. Metabolic changes, ER stress and UPR (unfolded protein response) contribute to muscle proteostasis dysregulation with active membrane remodeling (high levels of LC3BII/LC3BI) and accumulation of p62, suggesting imbalance in the autophagic process. Active lysosome biogenesis characterizes both LOPD PRE and POST, unparalleled by molecules involved in lysosome tethering (VAMP8, SNAP29, STX17, and GORASP2) and BNIP3. In conclusion this study reveals a specific signature that suggests ERT prolongation and molecular targets to ameliorate patient’s outcome.

Cardiac arrest in anti-mitochondrial antibody associated inflammatory myopathy

Insight into predictors of cardiac involvement in inflammatory myopathies is sparse. A negative prognostic role of anti-mitochondrial antibodies (AMA) has been noticed and is supported by the current case. We describe a male patient who at the age 40 suffered a cardiac arrest and over the following months experienced progressive heart failure, arrhythmias and proximal muscle weakness. Clinical, genetic and serologic testing and repeated imaging- and histopathological investigations resulted in a diagnosis of AMA-associated, necrotizing, inflammatory myositis with cardiac involvement. Besides a cardiac resynchronization therapy defibrillator, heart failure and antiarrhythmic drugs the patient received successive immunosuppressants, which improved skeletal muscle strength but not cardiac disease progression. At age 45 he died from end-stage heart failure. Clinicians must be aware of AMA-associated myositis as a cause of unclarified heart disease, even in patients with initially sparse extra-cardiac manifestations. Further knowledge of treatment strategies is highly needed for this disease entity.

Progressive neurological symptoms following a fall

A 58-year-old woman was transferred to a tertiary neurology unit with a 10-week history of progressive symmetrical proximal muscle weakness with associated myalgia, predominantly affecting the lower limbs. She had no visual disturbances, speech difficulties, hearing loss, dysphagia, fasciculation,

Immune-Mediated Necrotizing Myopathy: IMNM

Immune-mediated necrotizing myopathy (IMNM) is a heterogeneous disease that presents with subacute progressive proximal dominant muscle weakness clinically and prominent necrotic muscle fibers without invasion of inflammatory cells pathologically. IMNM is a disease that exclusively affects skeletal muscles, so the serum creatine kinase level usually increases prominently. It is thought to be an autoimmune disease because of the presence of two autoantibodies, anti-SRP and anti-HMGCR. Because muscle involvement is more severe than that in other forms of myositis, its functional prognosis is worse. Several immune-modifying therapies can improve the symptoms; therefore, intensive treatments should be started soon after diagnosis with IMNM.

Rituximab in the treatment of immune-mediated necrotizing myopathy: a review of case reports and case series.

Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX.Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.

Guillain-Barré Syndrome Associated with COVID-19: A Neurochallenge!!

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for Coronavirus disease 2019 (COVID-19), originated in Wuhan, China in the fall of 2019 which has soon become a global pandemic engulfing the entire world, presents with a myriad of symptoms from asymptomatic to severe disease with acute respiratory distress syndrome and multiple organ dysfunction and severe inflammatory response. New associations and clinical problems keep appearing with the new virus and here, we are reporting a case of Guillain-Barré syndrome (GBS) presented to us with complaints of progressive proximal muscle weakness and bilateral facial paralysis. The initial nerve conduction study was normal, but clinical examination showed us a picture of acute inflammatory demyelinating polyradiculoneuropathy and the patient was treated with intravenous immunoglobulin to which the patient responded dramatically. Repeat nerve conduction study showed typical features of GBS. Thus, a differential diagnosis of GBS should be kept in mind by all physicians/neurologists who encounter any neurological symptoms (especially muscle weakness) while treating or post-COVID-19 infection.

Clinical and Pathological Features of Lipid Storage Myopathy; A Retrospective Study of a Large Group from Iran

Background: Lipid storage myopathies (LSMs) are rare diseases. The phenotype and genotype of lipid metabolism disorders are heterogeneous and divided into two major groups. Constant or progressive proximal and axial muscle weakness associated with or without metabolic crisis, is often seen in patients with LSM such as primary carnitin deficiency (PCD) or multiple acyl-coenzyme a dehydrogenase deficiency disorder (MADD). On the other hand, rhabdomyolysis triggered by fasting, fever, or physical activity usually occurs in patients with disorders affecting intramitochondrial fatty acid transport and β-oxidation, such as carnitine palmitoyltransferase II deficiency (CPT2), mitochondrial trifunctional protein deficiency and very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD). Methods: In this cross-sectional study, we summarized the clinical profiles and muscle histology of 64 Iranian patients diagnosed with LSM by muscle biopsy. These patients were selected from 3000 patients referred for muscle biopsy to Toos and Mofid children’s hospitals during 2010 to 2016. Their affected siblings were also added to the study. Result: In our study 45.3% of the patients were men and 54.7% were women. Mean age of the patients was 27.05 years (SD: 14.26) and the mean age of onset of symptoms in these patients was 20.94 (SD: 14.25) years.  Most patients (70.3%) had proximal weakness and no bulbar involvement. Only 9.3% of the patients had a positive family history. Conclusion: LSMs are not incommon in Iran and their phenotype can mimic inflammatory myopathy or limb girdle muscular dystrophy. Overall the demographic and clinical features of LSMs in Iranian patients were similar to prior reports.

Early pulmonary manifestations of dermatomyositis: A case report

Introduction: Dermatomyositis (DM) is an idiopathic connective tissue disease with a wide range of systemic manifestations. Progressive proximal skeletal muscle weakness and symmetric and inflammatory infiltrates are the main clinical and histological features of DM. Case presentation: In this study, we report the case of a 43-year-old male with DM and early pulmonary manifestations. A 50 mg/g daily dose of prednisolone was administered for the case. The symptoms of muscle weakness improved after 2 weeks. Commonly, pulmonary diseases occur after the occurrence of other connective tissue diseases. However, in the present case, pulmonary manifestations were observed many years before the incidence of DM symptoms. Conclusions: The DM with pulmonary involvement is associated with worse outcomes; accordingly, a higher rate of mortality is reported among these patients. Based on the literature, the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are reliable markers for the diagnosis of DM, along with lung problems.

EP23 Symptomatic sarcoid myopathy: a rare extra-pulmonary manifestation of sarcoidosis

EP23 Symptomatic sarcoid myopathy: a rare extra-pulmonary manifestation of sarcoidosis

AUTOIMMUNE MYOPATHIES: P.296 The ProDERM study: A randomized, double-blinded, placebo controlled trial of IVIG (Octagam 10%) in patients with dermatomyositis

Dermatomyositis (DM) is a rare chronic autoimmune condition with characteristic skin manifestations and progressive proximal muscle weakness. Although treatments such as glucocorticoids and other immunosuppressive or immunomodulatory therapies including immunoglobulins are used, evidence supporting their efficacy in DM is limited. The ProDERM study aimed to investigate the efficacy and safety/tolerability of intravenous immunoglobulins (IVIG - Octagam 10%) in patients with DM in a prospective, parallel group, double-blind, randomized, placebo-controlled, international multicenter, phase III study.

MITOCHONDRIAL DISEASES & METABOLIC MYOPATHIES: P.313 Design of a phase 3 prospective clinical study for the treatment of thymidine kinase 2 deficiency (TK2d)

TK2d is an ultra-rare and often lethal disorder, caused by autosomal recessive mutations in TK2 resulting in mitochondrial DNA depletion and deletion. TK2d presents as progressive proximal muscle weakness in all patients; however, there is clinical heterogeneity, with a spectrum of severity and functional impairment. TK2d-reported categories were originally based on age of onset: infantile, juvenile/childhood, and late/adult-onset. Late-onset TK2d represents the smallest number of reported cases, with less available data than for the younger patients.

NEW GENES AND DISEASES / NGS & RELATED TECHNIQUES: P.333 Progressive proximal muscle weakness, myopathic muscle biopsy and a novel candidate gene

More than 200 new Mendelian disease gene discoveries have been published every year since the introduction of next-generation sequencing technologies. To date, almost 600 genes are associated with neuromuscular disorders. We present the phenotype of an Estonian girl harboring variants in a novel muscle disease candidate gene. The female patient was first noted to have exercise intolerance at age 3 years. Two years later, she presented with abnormal gait, toe walking, frequent falls, lumbar hyperlordosis, hyperextention of the knees, and valgus feet.

Perfil demográfico y clínico-funcional de pacientes con atrofia muscular espinal atendidos en el Instituto Teletón Santiago

Introducción: la atrofia muscular espinal (AME) es una enfermedad neuro-muscular (ENM) severa caracterizada por la degeneración de las motoneuronas alfa del asta anterior de la médula espinal, generando una debilidad progresiva de la musculatura proximal. La incidencia mundial se estima en 1/6.000-10.000 nacidos vivos. Contamos con escasos datos de las características de los pacientes con AME en la población chilena. Objetivo: Determinar magnitud, características demográficas y clínico funcionales de los pacientes con AME atendidos en el Instituto Teletón Santiago (ITS). Pacientes y Método: Estudio descriptivo transversal, basado en revisión del sistema informático ITS, fichas clínicas y encuesta telefónica. Resultados: Se identificaron 62 pacientes con AME con controles en ITS, 49 (79%), fueron incluidos. 30,6%, 36,7% y 32,7% corresponden a pacientes con AME 1, 2 y 3 respectivamente. Edad promedio 10,6 ± 6,6 años; pérdida de marcha edad mediana de 6,8 años en pacientes AME 3. 67,3% requieren algún tipo de asistencia ventilatoria, 44,9% presen-tan trastornos de deglución, 75,5% escoliosis, 49,0% subluxación o luxación de cadera, 79,6% retracciones articulares y 65,3% dolor. En participación, el 83% de las actividades de ocio se realizan dentro del hogar, principalmente de tipo tecnológico; 77,5% realiza salidas sociales. Conclusión: Las carac-terísticas clínico funcionales de los pacientes con AME, evidencian un grupo que presenta un alto nivel de dependencia en todos los tipos de la enfermedad, múltiples comorbilidades y alteraciones músculo-esqueléticas secundarias y por ello requiere de un programa de rehabilitación multidisciplinaria tal como lo describe la literatura internacional.

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.