Outcomes after intervention for enteral nutrition in patients with amyotrophic lateral sclerosis in multidisciplinary clinics.

INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications. METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes. RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome. DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.

Non-dystrophic myotonia: 2-year clinical and patient reported outcomes.

INTRODUCTION/AIMS: Consistency of differences between non-dystrophic myotonias over time measured by standardized clinical/patient-reported outcomes is lacking. Evaluation of longitudinal data could establish clinically relevant endpoints for future research. METHODS: Data from prospective observational study of 95 definite/clinically suspected non-dystrophic myotonia participants (six sites in the United States, United Kingdom, and Canada) between March 2006 and March 2009 were analyzed. Outcomes included: standardized symptom interview/exam, Short Form-36, Individualized Neuromuscular Quality of Life (INQoL), electrophysiological short/prolonged exercise tests, manual muscle testing, quantitative grip strength, modified get-up-and-go test. Patterns were assigned as described by Fournier et al. Comparisons were restricted to confirmed sodium channelopathies (SCN4A, baseline, year 1, year 2: n = 34, 19, 13), chloride channelopathies (CLCN1, n = 32, 26, 18), and myotonic dystrophy type 2 (DM2, n = 9, 6, 2). RESULTS: Muscle stiffness was the most frequent symptom over time (54.7%-64.7%). Eyelid myotonia and paradoxical handgrip/eyelid myotonia were more frequent in SCN4A. Grip strength and combined manual muscle testing remained stable. Modified get-up-and-go showed less warm up in SCN4A but remained stable. Median post short exercise decrement was stable, except for SCN4A (baseline to year 2 decrement difference 16.6% [Q1, Q3: 9.5, 39.2]). Fournier patterns type 2 (CLCN1) and 1 (SCN4A) were most specific; 40.4% of participants had a change in pattern over time. INQoL showed higher impact for SCN4A and DM2 with scores stable over time. DISCUSSION: Symptom frequency and clinical outcome assessments were stable with defined variability in myotonia measures supporting trial designs like cross over or combined n-of-1 as important for rare disorders.

Open-label pilot study of ranolazine for cramps in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Neuronal hyperexcitability (manifested by cramps) plays a pathological role in amyotrophic lateral sclerosis (ALS), and drugs affecting it may help symptomatic management and slow disease progression. We aimed to determine safety and tolerability of two doses of ranolazine in patients with ALS and evaluate for preliminary evidence of drug-target engagement by assessing muscle cramp characteristics. METHODS: We performed an open-label dose-ascending study of ranolazine in 14 individuals with ALS in two sequential cohorts: 500 mg (cohort 1) and 1000 mg (cohort 2) orally twice daily. Each had a 2-week run-in period, 4-week drug administration, and 6-week safety follow-up. Primary outcome was safety and tolerability. Exploratory measures included cramp frequency and severity, fasciculation frequency, cramp potential duration, ALS Functional Rating Scale---Revised score, and forced vital capacity. RESULTS: Six and eight participants were enrolled in cohorts 1 and 2, respectively. There were no serious adverse events. Two subjects in cohort 2 discontinued the drug due to constipation. The most frequent drug-related adverse event was gastrointestinal (40%). Cramp frequency decreased by 54.8% (95% confidence interval [CI], 39%-70.8%) and severity decreased by 46.3% (95% CI, 29.5-63.3%), which appeared to be dose-dependent, with decreased awakening due to cramps. Other outcomes showed no change. DISCUSSION: Ranolazine was well tolerated in ALS up to 2000 mg/day, with gastrointestinal side effects being the most frequent. Ranolazine reduced cramp frequency and severity, supporting its investigation for muscle cramps in a future placebo-controlled trial.

Primary lateral sclerosis (PLS) functional rating scale: PLS-specific clinimetric scale.

INTRODUCTION: Our research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS). METHODS: A prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy-seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro-Quality of Life (QoL), Schwab-England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment. RESULTS: The PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test-retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS-R were significantly higher. DISCUSSION: The PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period.

Investigation of the psychometric properties of the inclusion body myositis functional rating scale with rasch analysis.

INTRODUCTION: The Inclusion Body Myositis Functional Rating Scale (IBMRFS) is a 10-item clinician-rated ordinal scale developed for people with inclusion body myositis. METHODS: Single observations of the IBMFRS were collected from 132 patients. After Rasch analysis, modifications were made to the scale to optimize fit to the Rasch model while maintaining clinical validity and utility. RESULTS: The original IBMFRS did not fit the assumptions of the Rasch model because of multidimensionality of the scale. Items assessed local dependence, disordered step thresholds, and differential item functioning. Deconstructing the scale into upper limb (IBMFRS-UL) and lower limb (IBMFRS-LL) scales improved fit to the Rasch model. A 9-item scale with the swallowing item removed (IBMFRS-9) remained multidimensional but demonstrated the ability to discriminate patients along the severity continuum. IBMFRS-UL, IBMFRS-LL, and IBMFRS-9 scores were transformed to a 0-100 scale for comparability. DISCUSSION: This analysis has led to the development of 3 optimized versions of the IBMFRS. Muscle Nerve 60: 161-168, 2019.

An instrumented timed up and go in facioscapulohumeral muscular dystrophy.

INTRODUCTION: Instrumenting timed functional motor tasks may reveal a continuum of motor disability that predicts future motor dysfunction. METHODS: We performed a prospective study of the instrumented timed up and go (iTUG) test in genetically confirmed facioscapulohumeral muscular dystrophy (FSHD) participants using a commercially available system of wireless motion sensors. Patients returned within 2 weeks to determine test-retest reliability. Gait parameters in FSHD participants were compared with a normative database, FSHD clinical severity score, manual muscle testing, and patient-reported functional disability. RESULTS: Gait parameters in FSHD participants were significantly (P < 0.05) altered compared with normative values, and reliability was excellent (intraclass correlation coefficient 0.84-0.99). Stride velocity and trunk sagittal range of motion had moderate to strong correlations to other FSHD disease measures. DISCUSSION: The iTUG was reliable, abnormal in FSHD, and could distinguish between participants with differing disease severities. Instrumenting timed functional tasks may prove to be useful in FSHD clinical trials. Muscle Nerve 57: 503-506, 2018.

Using automated electronic medical record data extraction to model ALS survival and progression.

BACKGROUND: To assess the feasibility of using automated capture of Electronic Medical Record (EMR) data to build predictive models for amyotrophic lateral sclerosis (ALS) outcomes. METHODS: We used an Informatics for Integrating Biology and the Bedside search discovery tool to identify and extract data from 354 ALS patients from the University of Kansas Medical Center EMR. The completeness and integrity of the data extraction were verified by manual chart review. A linear mixed model was used to model disease progression. Cox proportional hazards models were used to investigate the effects of BMI, gender, and age on survival. RESULTS: Data extracted from the EMR was sufficient to create simple models of disease progression and survival. Several key variables of interest were unavailable without including a manual chart review. The average ALS Functional Rating Scale - Revised (ALSFRS-R) baseline score at first clinical visit was 34.08, and average decline was - 0.64 per month. Median survival was 27 months after first visit. Higher baseline ALSFRS-R score and BMI were associated with improved survival, higher baseline age was associated with decreased survival. CONCLUSIONS: This study serves to show that EMR-captured data can be extracted and used to track outcomes in an ALS clinic setting, potentially important for post-marketing research of new drugs, or as historical controls for future studies. However, as automated EMR-based data extraction becomes more widely used there will be a need to standardize ALS data elements and clinical forms for data capture so data can be pooled across academic centers.

FUS G559A Mutation in a Patient with a Frontotemporal Dementia-Motor Neuron Disease Compatible Syndrome: A Case Report.

Fused in sarcoma (FUS) mutations cause frontotemporal dementia (FTD) and motor neuron disease (MND). Here, we describe a 43-year-old man with progressive behavioral and cognitive change, myelopathy, clinical and electrophysiologic evidence of MND, and a FUS variant of unknown significance (VUS). This VUS, a heterozygous G559A transition (Gly187Ser), was previously reported in a patient with sporadic MND and affects important FUS biophysical properties. While this rare variant's presence in a second patient with a related neurodegenerative syndrome does not establish pathogenicity, it raises the question of whether its association with our patient is coincidental and increases the possibility that FUS G559A is pathogenic.

Conducting a bayesian multi-armed trial with response adaptive randomization for comparative effectiveness of medications for CSPN.

Background: Response adaptive randomization is popular in adaptive trial designs, but the literature detailing its execution is lacking. These designs are desirable for patients/stakeholders, particularly in comparative effectiveness research, due to the potential benefits including improving participant buy-in by providing more participants with better treatment during the trial. Frequentist approaches have often been used, but adaptive designs naturally fit the Bayesian methodology; it was developed to deal with data as they come in by updating prior information. Methods: PAIN-CONTRoLS was a comparative-effectiveness trial utilizing Bayesian response adaptive randomization to four drugs, nortriptyline, duloxetine, pregabalin, or mexiline, for cryptogenic sensory polyneuropathy (CSPN) patients. The aim was to determine which treatment was most tolerable and effective in reducing pain. Quit and efficacy rates were combined into a utility function to develop a single outcome, which with treatment sample size, drove the adaptive randomization. Prespecified interim analyses allowed the study to stop for early success or update the randomization probabilities to the better-performing treatments. Results: Seven adaptations to the randomization occurred before the trial ended due to reaching the maximum sample size, with more participants receiving nortriptyline and duloxetine. At the end of the follow-up, nortriptyline and duloxetine had lower probabilities of participants that had stopped taking the study medication and higher probabilities were efficacious. Mexiletine had the highest quit rate, but had an efficacy rate higher than pregabalin. Conclusions: Response adaptive randomization has become a popular trial tool, especially for those utilizing Bayesian methods for analyses. By illustrating the execution of a Bayesian adaptive design, using the PAIN-CONTRoLS trial data, this paper continues the work to provide literature for conducting Bayesian response adaptive randomized trials.

Primary lateral sclerosis natural history study - planning, designing, and early enrollment.

Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.

A novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis: Jaw muscle synergy.

OBJECTIVE: To identify a novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis (ALS) based on jaw muscle synergies. METHODS: Muscle synergies were extracted from the surface electromyographic recordings of five jaw muscles during speech in 11 individuals at the prodromal or symptomatic stages of bulbar ALS and 10 neurologically-healthy controls, using non-negative matrix factorization. The disrupted muscle synergies in ALS were identified; their efficacy in differentiating individuals with ALS from healthy controls and relation to the previously-reported kinematic and functional speech deficits were determined. RESULTS: An antagonist synergy (i.e., masseter × digastric) was significantly disrupted in ALS, which differentiated individuals with ALS from healthy controls with 82% sensitivity and 90% specificity. Such a disruption occurred prodromally and was associated with slowed jaw movement and reduced speaking rate across the range of severity. CONCLUSIONS: The disruption of jaw antagonist synergy in ALS likely reflects the impact of impaired neural drive on the coordinative functioning of bulbar muscles, which may be used to assess bulbar motor involvement. SIGNIFICANCE: Jaw antagonist synergy shows promise as a novel physiologic marker of bulbar motor involvement in ALS, which has the potential to serve as a quantitative measurement tool for bulbar assessment.

Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord.

Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate treatment has a neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) G93A mice with oxaloacetate and evaluated their neuromuscular function and lifespan. Treatment with oxaloacetate beginning in the presymptomatic stage significantly improved neuromuscular strength measured during the symptomatic stage in the injected mice compared to the non-treated group. Oxaloacetate treatment starting in the symptomatic stage significantly delayed limb paralysis compared with the non-treated group. For lifespan analysis, oxaloacetate treatment did not show a statistically significant positive effect, but the treatment did not shorten the lifespan. Mechanistically, SOD1G93A mice showed increased levels of tumor necrosis factor-α (TNFα) and peroxisome proliferative activated receptor gamma coactivator 1α (PGC-1α) mRNAs in the spinal cord. However, oxaloacetate treatment reverted these abnormal levels to that of wild-type mice. Similarly, the altered expression level of total NF-κB protein returned to that of wild-type mice with oxaloacetate treatment. These results suggest that the beneficial effects of oxaloacetate treatment in SOD1G93A mice may reflect the effects on neuroinflammation or bioenergetic stress.

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial.

Importance: Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN. Objective: To determine which medication (pregabalin, duloxetine, nortriptyline, or mexiletine) is most effective for reducing neuropathic pain and best tolerated in patients with CSPN. Design, Setting, and Participants: From December 1, 2014, through October 20, 2017, a bayesian adaptive, open-label randomized clinical comparative effectiveness study of pain in 402 participants with CSPN was conducted at 40 neurology care clinics. The trial included response adaptive randomization. Participants were patients with CSPN who were 30 years or older, with a pain score of 4 or greater on a numerical rating scale (range, 0-10, with higher scores indicating a higher level of pain). Participant allocation to 1 of 4 drug groups used the utility function and treatment's sample size for response adaptation randomization. At each interim analysis, a decision was made to continue enrolling (up to 400 participants) or stop the whole trial for success (80% power). Patient engagement was maintained throughout the trial, which helped guide the study and identify ways to communicate and disseminate information. Analysis was performed from December 11, 2015, to January 19, 2018. Interventions: Participants were randomized to receive nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). Main Outcomes and Measures: The primary outcome was a utility function that was a composite of the efficacy (participant reported pain reduction of ≥50% from baseline to week 12) and quit (participants who discontinued medication) rates. Results: Among the 402 participants (213 men [53.0%]; mean [SD] age, 60.1 [13.4] years; 343 White [85.3%]), the utility function of nortriptyline was 0.81 (95% bayesian credible interval [CrI], 0.69-0.93; 34 of 134 [25.4%] efficacious; and 51 of 134 [38.1%] quit), of duloxetine was 0.80 (95% CrI, 0.68-0.92; 29 of 126 [23.0%] efficacious; and 47 of 126 [37.3%] quit), pregabalin was 0.69 (95% CrI, 0.55-0.84; 11 of 73 [15.1%] efficacious; and 31 of 73 [42.5%] quit), and mexiletine was 0.58 (95% CrI, 0.42-0.75; 14 of 69 [20.3%] efficacious; and 40 of 69 [58.0%] quit). The probability each medication yielded the highest utility was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine. Conclusions and Relevance: This study found that, although there was no clearly superior medication, nortriptyline and duloxetine outperformed pregabalin and mexiletine when pain reduction and undesirable adverse effects are combined to a single end point. Trial Registration: ClinicalTrials.gov Identifier: NCT02260388.

Use of Capillary Electrophoresis Immunoassay to Search for Potential Biomarkers of Amyotrophic Lateral Sclerosis in Human Platelets.

Capillary electrophoresis immunoassay (CEI), also known as capillary western technology, is becoming a method of choice for screening disease relevant proteins and drugs in clinical trials. Reproducibility, sensitivity, small sample volume requirement, multiplexing antibodies for multiple protein labeling in the same sample, automated high-throughput ability to analyze up to 24 individual samples, and short time requirement make CEI advantageous over the classical western blot immunoassay. There are some limitations of this method, such as the inability to utilize a gradient gel (4%-20%) matrix, high background with unrefined biological samples, and commercial unavailability of individual reagents. This paper describes an efficient method for running CEI in a multiple assay setting, optimizing protein concentration and primary antibody titration in one assay plate, and providing user-friendly templates for sample preparation. Also described are methods for measuring pan TDP-43 and phosphorylated TDP-43 derivative in platelet lysate cytosol as part of the initiative in blood-based biomarker development for neurodegenerative diseases.

Satisfactory Response With Achieving Maintenance Low-Dose Prednisone in Generalized Myasthenia Gravis.

OBJECTIVES: To estimate the satisfactory response rate (SR%) with achieving maintenance, low-dose prednisone in acetylcholine receptor antibody-positive generalized myasthenia gravis. METHODS: In this retrospective study, we estimate the SR% as defined by (remission/minimal manifestations status for at least 6 months using 7.5 mg or less of prednisone daily, for maintenance treatment at 2, 4, and 6 years after symptoms onset) for patients who were not taking steroid-sparing immunosuppressant (SSI) as a primary outcome and for patients taking an SSI as a secondary outcome. RESULTS: Forty-five patients were not taking an SSI at 2 years, 34 patients at 4 years, and 17 patients at 6 years; SR% was 44.4%, 64.7%, and 58.8%, respectively. Thirty-six patients were taking an SSI at 2 years, 22 patients at 4 years, and 15 patients at 6 years; the SR% was 50.0%, 45.4%, and 66.7%, respectively. CONCLUSIONS: Nearly half of the generalized myasthenia gravis patients who were not taking an SSI achieved an SR.

Less is More in Diabetic Neuropathy Diagnosis: Comparison of Quantitative Sudomotor Axon Reflex and Skin Biopsy.

OBJECTIVES: To compare the frequency of abnormalities in epidermal nerve fiber density (ENFD) and quantitative sudomotor axon reflex (QSART) in patients with diabetic distal symmetric polyneuropathy (DSPN). METHODS: Nerve conduction studies, ENFD, and QSART data were obtained pre- and postexercise, in patients enrolled in a prospective diabetic neuropathy study. McNemar's test was applied to compare the yield of ENFD and QSART. RESULTS: Eighteen patients (58 ± 4 years) were enrolled, with 36 data collection points. In diabetic DSPN and diabetic large fiber DSPN (DSPN-L), abnormal ENFD (77% and 100% respectively) is more frequent than abnormal QSART (39% and 35%, respectively) (P value = 0.001 in diabetic DSPN and P value = 0.0002 in diabetic DSPN-L), whereas in diabetic small fiber DSPN (DSPN-S), both tests have similar yields (47%). CONCLUSIONS: ENFD has a high diagnostic yield in diabetic DSPN and DSPN-L. Including QSART data adds little to the sensitivity of EFND in DSPN-S.

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

BACKGROUND: In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. RESULTS: A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. CONCLUSION: This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis).

Amyotrophic lateral sclerosis (ALS), a rapidly progressive, invariably fatal disease, involves mixed upper and lower motor neurons in different spinal cord regions. Patients with bulbar onset progress more rapidly than patients with limb onset or with a lower motor neuron presentation. Recent descriptions of regional variants suggest some patients have ALS isolated to a single spinal region for many years, including brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar palsy. Clearer definitions of regional variants will have implications for prognosis, understanding the pathophysiology of ALS, identifying genetic factors related to slower disease progression, and future planning of clinical trials.

Pompe disease: literature review and case series.

Pompe disease is a rare multi-systemic metabolic myopathy caused by autosomal recessive mutations in the acidic alpha glucosidase (GAA) gene. Significant progress had been made in the diagnosis and management of patients with Pompe disease. Here, we describe our experience with 12 patients with various forms of Pompe disease including 4 potentially pathogenic, novel GAA variants. We also review the recent the recent advances in the pathogenesis, diagnosis, and treatment of individuals with Pompe disease.