Diagnosis Of Late-onset Pompe Disease Research Articles

Pompe and Circumstance: A Cautionary Tale of Anchoring Bias and Delayed Diagnosis of Late-onset Pompe Disease in a Patient with a History of Pelvic Radiation (P11-11.006)

Pompe and Circumstance: A Cautionary Tale of Anchoring Bias and Delayed Diagnosis of Late-onset Pompe Disease in a Patient with a History of Pelvic Radiation (P11-11.006)

Diagnostic delay in late-onset Pompe disease among Chinese patients: A retrospective study.

Surveys and retrospective studies have revealed considerable delays in diagnosing late-onset Pompe disease (LOPD) in China, where the contributing factors remain poorly represented. Our study analyzed the diagnostic journey of 34 LOPD patients seen at our neuromuscular clinic from 2005 to 2022. We defined diagnostic delay as the time from the onset of the first relevant symptoms and laboratory findings suggestive of LOPD to the eventual diagnosis, and we constructed a correlation matrix to assess relationships among these variables. The cohort consisted of 34 patients with an equal male-to-female ratio, and the mean age at diagnosis was 27.68 ± 10.03 years. We found the median diagnostic delay to be 5 years, with a range of 0.3 to 20 years, with 97.1% having been misdiagnosed previously, most commonly with "Type II Respiratory insufficiency" (36.7%). Notably, patients at earlier onset (mean age, 18.19 years vs. 31 years; p < 0.005) tended to have higher creatine kinase (CK) levels. Furthermore, 92.6% reported difficulty in sitting up from a supine position since childhood. Our research emphasizes the role of early indicators like dyspnea and difficulty performing sit-ups in adolescents for timely LOPD diagnosis and treatment initiation. The importance of early high-risk screening using dried blood spot testing cannot be overstated.

Screening for late-onset Pompe disease in Internal Medicine departments in Spain

BackgroundThe screening of high-risk populations using dried blood spots (DBS) has allowed the rapid identification of patients with Pompe disease, mostly in Neurology departments. The aim of the study was to determine the prevalence of late-onset Pompe disease (LOPD) among patients not previously diagnosed or tested for this entity despite presenting possible signs or symptoms of the disease in Internal Medicine departments in Spain.MethodsThis epidemiological, observational, cross-sectional, multicenter study included a single cohort of individuals with clinical suspicion of LOPD seen at Internal Medicine departments in Spain. The diagnosis of LOPD was initially established on the basis of the result of DBS. If decreased enzyme acid-alpha-1,4-glucosidase (GAA) activity was detected in DBS, additional confirmatory diagnostic measurements were conducted, including GAA activity in lymphocytes, fibroblasts, or muscle and/or genetic testing.ResultsThe diagnosis of LOPD was confirmed in 2 out of 322 patients (0.6%). Reasons for suspecting LOPD diagnosis were polymyositis or any type of myopathy of unknown etiology (in one patient), and asymptomatic or pauci-symptomatic hyperCKemia (in the other). The time between symptom onset and LOPD diagnosis was 2.0 and 0.0 years. Both patients were asymptomatic, with no muscle weakness. Additionally, 19.7% of the non-LOPD cases received an alternative diagnosis.ConclusionsOur study highlights the existence of a hidden population of LOPD patients in Internal Medicine departments who might benefit from early diagnosis and early initiation of potential treatments.

Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Multisystem presentation of Late Onset Pompe Disease: what every consulting neurologist should know.

Pompe disease is a rare, autosomal recessive, lysosomal disorder caused by deficiency of alpha glucosidase (GAA). It leads to the accumulation of glycogen in body tissues, with severe myopathy and cardiomegaly as a hallmark of the classic infantile form. Non-classical, or late onset, Pompe disease (LOPD) manifests after 12 months of age or in adulthood. The clinical heterogeneity of LOPD causes delay in diagnosis and pharmacological treatment. In the Polish population, it is still underdiagnosed, and the time from onset to diagnosis remains a cause for concern. Although typically patients present with proximal muscle weakness, high CK or early respiratory insufficiency, they can also suffer from multiple symptoms from other organs. Patients may present with arrhythmias, vascular abnormalities including aneurysms or dilative arteriopathy, gastric or urinary symptoms, or musculoskeletal pathologies. A high index of suspicion among neurologists consulting internal medicine wards would aid early diagnosis of LOPD, while a multidisciplinary approach with the involvement of other specialists can reduce the risk of complications and improve the prognosis for LOPD patients. Patients who manifest with musculoskeletal and respiratory symptoms are prone to be diagnosed sooner than individuals with non-muscular symptoms, and therefore it is important to raise awareness of other manifestations of this disease.

A challenging etiology of myopathy: The late-onset Pompe disease.

Pompe disease is a rare metabolic disorder that is characterized by the deficiency of the acid aglucosidase. As a result, glycogen accumulates in several tissues including motor neurons, skeletal, cardiac, and smooth muscles. The course of the disease varies according to the type of mutations, and the clinical phenotype can be affected by the enzyme levels. Late-onset Pompe disease (LOPD) is a challenging issue for clinicians as it has a milder phenotype with later onset of symptoms and slower disease progression. One of the most important differentials in the diagnosis of LOPD is inflammatory myositis as both diseases have some common clinical and laboratory features. Herein, we presented a 30-year-old female patient initially diagnosed as polymyositis and treated with immunosuppressive therapy without a benefit on her symptoms and later diagnosed as LOPD.

Late-onset Pompe disease - literature review and summary of current knowledge

Introduction: Pompe disease is a glycogen storage disorder caused by the deficient activity of the lysosomal enzyme acid α-glucosidase (GAA). Mutations in the GAA gene lead to the accumulation of glycogen in different organs. In a late-onset form (late-onset Pompe disease), the disease is characterized by slow, progressive proximal limb and respiratory muscle weakness. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. LOPD is treated with enzyme replacement therapy (ERT). Purpose: Summary of currently knowladge about Late-onset Pompe disease - characteristic, diagnosis and treatment. Methods: A review of literature available in the PubMed database and Google Scholar. by searching for keywords: Pompe disease, Late-onset Pompe disease, LOPD, alglucosidase- α. Results: The diagnosis of late-onset Pompe disease can often be difficult. It is a very rare disease and the clinical presentation is similar to other neuromuscular disorders, such as Duchenne and Backer muscular dystrophies, glycogenosis or autoimmune or mitochondrial myopathies and others. Despite available specific enzyme replacement therapy LOPD is progressive. Patients require support from a multidisciplinary team of specialists, including care from neurologists, pulmonologists or physiotherapists. Conclusion: Although rare, Pompe disease should be considered in patients with proximal paresis and respiratory failure. More research into LOPD can help increasing precocity of diagnosis and treat it more effectively.

VP.33 Quantification of the burden, unmet needs, management, and COVID 19 impact of living with Pompe disease in the UK: results of an online patient survey

Pompe disease is a rare, progressive, multisystemic disease. Here we report results of an online quantitative survey of people living with late-onset Pompe disease (LOPD) in the UK, with the aim to better understand and quantify their experiences throughout the disease journey. 37 participants (male, n=19 [51%]; mean age, 54.1 years; mean age at symptom onset, 33.2 years; mean age at LOPD diagnosis, 42.5 years; received ≥1 misdiagnosis, n=17 [46%]) completed the survey consisting of 42 questions in January 2022. Results revealed that most participants received assistance with day-to-day living (n=30, 81%), with the most frequent LOPD-associated symptoms being walking difficulties (n=35, 95%), fatigue (n=35, 95%) and muscle weakness (n=34, 92%). 26 participants (70%) were being treated with standard-of-care enzyme replacement therapy (ERT) at the time of the survey; 14 (54%) of those for >10 years and 20 (77%) deeming their condition to have deteriorated since treatment began. Several patients receiving ERT mentioned the need for more efficacious or novel treatments (n=6, 23%) and the use of a delivery method less invasive than intravenous (n=5, 19%) as desired improvements to ERT. Many participants stated the provision of ancillary therapies (eg physiotherapy [n=27, 73%], dietary advice [n=18, 49%]) and mental health counselling [n=17, 46%]) would help them better manage their condition. The COVID-19 pandemic has been a period of increased anxiety and physical deterioration for many participants, with 50% (n=13) of those on ERT stating their treatment had been interrupted due to the pandemic. However, several people mentioned initiation of home-based/self-administered therapies (n=4, 11%) and reduced travel (n=5, 14%) as beneficial outcomes of the pandemic. Findings from this study further characterise the challenges faced by people living with LOPD, highlighting the need for varied patient support and more efficacious treatment options.

P.84 Gait analysis of patients with Pompe disease using a portable system

The development of new outcome measures that can identify changes in muscle function is an unmet need for patients with neuromuscular diseases. We have used a new portable device to assess gait features of a cohort of patients with late onset Pompe disease (LOPD) and compare it with gender and age matched controls. We performed a cross-sectional study analyzing different features of gait in LOPD patients and controls. We used the new device, Ephion mobility, consisting of a set of commercial wearables interconnected within a platform that permits to register a complete cluster of biomechanical data out of the functional test performed. The connected wearables include inertial measurement units (IMU), electromyography (EMG) sensors and plantar pressure sensors embedded in shorts and insoles that allow measurement of kinematics, spatio-temporal, plantar pressure, muscle activity and cardiovascular features. Individuals wore the sensors while performing the six minute walk test (6MWT) and the 10 meter walk/run (10M). We included 18 LOPD patients (10 women) patients with a genetic diagnosis of LOPD and 27 controls. All LOPD patients were symptomatic and treated with enzyme replacement therapy. Distance walked in the 6MWT was significantly shorter for LOPD (423±103.5m) compared to controls (655±140m). We observed significant differences in the gait pattern between both groups across kinematics, spatio-temporal, plantar pressure, and EMG signals. We observed that LOPD had an increase oscillation of the trunk and pelvis during stance phase associated to a longer extension of the knee during stance and an inversion of the foot. Moreover, there are significant differences between muscle strength of the knee flexors and gluteus muscles both at rest and when walking. We observed longer co-contraction of the knee flexor and extensors while walking compared to control. There was a decrease in the ground reaction force (GRF) in the heel strike and an increase in the mid-stance resulting in a flattened GRF profile. The Ephion mobility device is an easy-to-use measurement to study different features of gait. We observed significant differences between the gait pattern of LODP patients and controls in this cross-sectional study suggesting multiple potential outcome measurements to distinguish between these two populations. Longitudinal studies are needed to identify if these measurements can capture disease progression over time.

High-risk screening of late-onset Pompe disease: A different early portrait in China.

IntroductionThe lack of knowledge regarding the differences between Chinese and other ethnicities in the early manifestation of late-onset Pompe disease (LOPD) prohibits the development of an effective screening strategy. We conducted a multicenter screening study to determine LOPD prevalence in high-risk populations and define the early manifestation of LOPD in China.MethodsBetween August 2020 and April 2021, the participants were prospectively identified through medical examination at 20 centers from inpatient departments and outpatient neuromuscular clinics in China. The inclusion criteria were as follows: (1) age ≥ 1 year and (2) either one of the following conditions: (a) persistent hyperCKemia, (b) muscle weakness of the axial and/or limb-girdle muscles, or (c) unexplained restrictive respiratory insufficiency (RI). Enzymatic activity of acid α-glucosidase (GAA) was measured in a dried blood spot (DBS) using a tandem mass spectrometry (MS/MS) assay. Next-generation sequencing (NGS) was used to evaluate all samples with decreased GAA activity, searching for GAA mutations and pseudodeficiency alleles.ResultsAmong the 492 cases, 26 positive samples (5.3%) were detected in the DBS test. Molecular studies confirmed a diagnosis of LOPD in eight cases (1.6%). Using MS/MS assay, GAA activities in individuals with pseudodeficiency could be distinguished from those in patients with LOPD. The median interval from the onset of symptoms to diagnosis was 5 years. All patients also showed RI, with a mean forced vital capacity (FVC) of 48%, in addition to axial/proximal muscle weakness. The creatine kinase (CK) level ranged from normal to no more than 5-fold the upper normal limit (UNL). LOPD with isolated hyperCKemia was not identified.ConclusionLess frequent hyperCKemia and predominant RI depict a different early portrait of adult Chinese patients with LOPD. A modified high-risk screening strategy should be proposed for the early diagnosis of Chinese patients with LOPD.

A Multidisciplinary Perspective Addressing the Diagnostic Challenges of Late-Onset Pompe Disease in the Arabian Peninsula Region Developed From an Expert Group Meeting.

Pompe disease is a rare, metabolic, autosomal recessive disorder. Early diagnosis is critical for progressive Pompe disease as delays can significantly alter the clinical course of the disease. Diagnostic modalities, including dried blood spot testing and genetic testing, are available and are effective for diagnosing patients with late-onset Pompe disease (LOPD). However, clinicians face numerous clinical challenges related to the diagnosis of the disease. Two expert group committee meetings, involving 11 experts from the United Arab Emirates, Kuwait, the Kingdom of Saudi Arabia, and Oman, were convened in October 2019 and November 2020 respectively to develop a uniform diagnostic algorithm for the diagnosis of pediatric and adult LOPD in the Arabian Peninsula region. During the first meeting, the specialty-specific clinical presentation of LOPD was defined. During the second meeting, a diagnostic algorithm was developed after a thorough validation of clinical presentation or symptoms, which was performed with the aid of existing literature and expert judgement. A consensus was reached on the diagnostic algorithm for field specialists, such as neurologists, rheumatologists, general practitioners/internal medicine specialists, orthopedic specialists, and pulmonologists. This specialty-specific diagnostic referral algorithm for pediatric and adult LOPD will guide clinicians in the differential diagnosis of LOPD.

Ultrasonography of abdominal muscles: Differential diagnosis of late-onset Pompe disease and myotonic dystrophy type 1.

IntroductionAxial muscles are involved earlier and to a greater extent in late-onset Pompe disease (LOPD) than in myotonic muscular dystrophy type 1 (DM1). We aimed to evaluate abdominal muscles in LOPD compared in DM1 using muscle ultrasonography.MethodsPatients with LOPD (n = 3), DM1 (n = 10), and age- and gender-matched healthy subjects (n = 34) were enrolled for muscle ultrasonography. Patients with LOPD and DM1 were 20 to 59 years of age with a disease duration ranging between 7 and 30 years. A multifrequency linear transducer was used to evaluate quality and thickness in the abdominal muscles and extremities.ResultsThe quantitative muscle echo score revealed a higher Z score in abdominal muscles in Patients with LOPD (scores were relatively normal for the biceps and flexor digitorum groups). Patients with LOPD had significantly lower abdominal muscle thickness than patients with DM1. Abdominal muscle strength was significantly correlated with the muscle echogenicity, trunk impairment scale, and trunk control test. The extremities' sum score was correlated with the total Medical Research Council score.DiscussionThe increased quantitative muscle score in abdominal muscles, sparing the biceps and flexor digitorum groups, may offer differential diagnosis between LOPD and DM1. Ultrasound can easily access abdominal muscles and investigate muscle echogenicity and thickness. A quantitative approach using muscle echogenicity rather than muscle thickness may provide a greater correlation with trunk muscle function.

Avalglucosidase Alfa (Nexviazyme)

&#x0D; CADTH recommends that Nexviazyme be reimbursed by public drug plans for the long-term treatment of patients with late-onset Pompe disease (LOPD) if certain conditions are met.&#x0D; Nexviazyme should only be covered to treat patients who have a confirmed diagnosis of LOPD, are able to walk, and have never received Myozyme before or were unable to tolerate Myozyme during the first year of treatment. Nexviazyme should not be covered to treat patients who have known Pompe-specific enlargement of the heart muscle, have severe disease, or are unable to perform repeated forced vital capacity (FVC percent predicted) measurements between 30% and 85%.&#x0D; Nexviazyme should only be reimbursed if prescribed by a clinician experienced in treating lysosomal storage diseases or other types of neuromuscular diseases and the price is less costly than Myozyme for the treatment of patients with LOPD.&#x0D;

A Qualitative Study: Mothers' Experiences of Their Child's Late-Onset Pompe Disease Diagnosis Following Newborn Screening.

Pompe disease was added to the United States recommended uniform screening panel in 2015 to avoid diagnostic delay and implement prompt treatment, specifically for those with infantile-onset Pompe disease (IOPD). However, most newborns with abnormal newborn screening (NBS) for Pompe disease have late-onset Pompe disease (LOPD). An early diagnosis of LOPD raises the question of when symptoms will arise which is challenging for parents, patients, and providers managing an LOPD diagnosis. This study aimed to characterize mothers’ experiences of their child’s LOPD diagnosis and medical monitoring. A qualitative descriptive approach was chosen to gain an in-depth understanding of parental experiences. Eight mothers were interviewed about their experiences with positive NBS and diagnosis, experiences with living with the diagnosis, and experiences with medical monitoring. Interview transcripts were analyzed through conventional content analysis. Negative emotions like fear were more frequent with communication of NBS results. Participants expressed uncertainty surrounding age of symptom onset and the future. The medical monitoring experience increased worry but participants expressed that being vigilant with management reassured them. Parental emotions shifted to thankfulness and reassurance with time and education. These findings can provide guidance to providers about the psychosocial implications of receiving positive NBS results and an LOPD diagnosis.

IperCKemia asintomatica: la malattia di Pompe late-onset

The paper reports the case of a 7-year-old boy who presented with elevated alanine and aspartate transaminases. Further investigations demonstrated elevated creatine kinase (CK), so an underlying metabolic disorder was investigated even in absence of clinical manifestations. Dried blood spot (DBS) screening test for acid α-glucosidase (AAG) enzyme activity was below normal levels and molecular genetic testing for AAG gene demonstrated pathogenic mutations. The diagnosis of late-onset Pompe disease (LOPD) was finally confirmed. Thanks to the early diagnosis, the child would be under close surveillance and would timely commence enzyme replacement therapy (ERT), improving the prognosis of the disease.&lt;br&gt; The diagnostic delay in patients with LOPD is still common, namely between about 5 and 30 years. Clinicians need a high index of suspicion to recognize this condition as it is a rare disease and the heterogeneous clinical presentation can mimic the presentation of other neuromuscular disorders.&lt;br&gt; Diagnostic laboratory tests are quite fast and reliable to detect the enzymatic deficiency and enzyme replacement therapy (ERT) is available and improves long-term outcomes. Thus, it is of absolute importance that clinicians should consider the possibility of LOPD in patients who present with asymptomatic hyperCKemia.

Late onset Pompe Disease in India – Beyond the Caucasian phenotype

We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 ± 9.7 years and 15.8 ± 12.1 years respectively was identified. All patients had lower extremity limb-girdle muscle weakness. Seven required ventilatory support and seven used mobility assists. Of the four who used both assists, two received ventilatory support prior to wheelchair use. Cardiac involvement was seen in eight patients with various combinations of left ventricular hypertrophy, tricuspid regurgitation, cardiomyopathy, dilated ventricles with biventricular dysfunction and aortic regurgitation. Amongst 20 biochemically diagnosed patients (low residual GAA enzyme activity) GAA genotypes of 19 patients identified homozygous variants in eight and compound heterozygous in 11: 27 missense, 3 nonsense, 2 initiator codon, 3 splice site and one deletion. Nine variants in 7 patients were novel. The leaky Caucasian, splice site LOPD variant, c.−32−13T>G mutation was absent. This first study from India provides an insight into a more severe LOPD phenotype with earlier disease onset at 9.9 years compared to 33.3 years in Caucasian patients, and cardiac involvement more than previously reported. The need for improvement in awareness and diagnosis of LOPD in India is highlighted.

Central nervous system involvement in late-onset Pompe disease: clues from neuroimaging and neuropsychological analysis.

Late-onset Pompe disease (LOPD) is a rare, multisystem disorder that is well established to mainly impair skeletal muscle function. Systematic studies exploring brain functions in LOPD are lacking. The aim of this study was to detect morphological and functional brain alterations as well as neuropsychological impairment in LOPD. We studied 21 patients (10 male, mean age 49±18.4years) with defined diagnosis of LOPD, divided into two groups: one with pre-symptomatic hyperCKemia with no muscle weakness and the second with limb-girdle muscle weakness. All patients underwent 3T magnetic resonance imaging (MRI) to obtain morphological/angiographic evaluation as well as normalized cortical brain volume and resting-state functional MRI. Fazekas score was applied to quantify white matter lesions, whereas Smoker's criteria were used to examine dolichoectasia. A complete neuropsychological assessment was performed. The MRI data showed that 12/21 patients (57%) demonstrated signs of cerebral vasculopathy, with a Fazekas score >2 in 67%. According to Smoker's criteria, 11/21 patients (52%) had a dolichoectasia of the vertebrobasilar system; an intracranial aneurysm was detected in 3/21 patients (14%). Resting-state functional MRI demonstrated significantly decreased brain connectivity in the salience network with a more relevant reduction in the bilateral middle and superior frontal gyrus. Gray matter atrophy correlated with age and disease duration. A mild impairment in executive functions was also identified. In this LOPD cohort the results showed morphological and functional brain alterations with mild neuropsychological dysfunction, mainly in the limb-girdle muscle weakness group. Cerebrovascular alterations seemed to be not related to common risk factors, suggesting a major role of enzymatic deficiency in the pathogenesis of brain abnormalities.

Acute respiratory failure as presentation of late-onset Pompe disease complicating the diagnostic process as a labyrinth: a case report

Background: Acute respiratory failure can be triggered by several causes, either of pulmonary or extra-pulmonary origin. Pompe disease, or type II glycogen storage disease, is a serious and often fatal disorder, due to a pathological accumulation of glycogen caused by a defective activiy of acid α-glucosidase (acid maltase), a lysosomal enzyme involved in glycogen degradation. The prevalence of the disease is estimated between 1 in 40,000 to 1 in 300,000 subjects. Case presentation: This case report describes a difficult diagnosis of late-onset Pompe disease (LOPD) in a 52 year old Caucasian woman with acute respiratory failure requiring orotracheal intubation and subsequent tracheostomy for long-term mechanical ventilation 24 h/day. Despite a complex diagnostic process including several blood tests, bronchoscopy with BAL, chest CT, brain NMR, electromyographies, only a muscle biopsy allowed to reach the correct diagnosis. Discussion: The most frequent presentation of myopathies, including LOPD, is proximal limb muscle weakness. Respiratory related symptoms (dyspnea on effort, reduced physical capacity, recurrent infections, etc.) and respiratory failure are often evident in the later stages of the diseases, but they have been rarely described as the onset symptoms in LOPD. In our case, a third stage LOPD, the cooperation between pulmonologists and neurologists was crucial in reaching a correct diagnosis despite a very complex clinical scenario due to different confounding co-morbidities as potential causes of respiratory failure and an atypical presentation. In this patient, enzyme replacement therapy with infusion of alglucosidase alfa was associated with progressive reduction of ventilatory support to night hours, and recovery of autonomous walking.

Acute respiratory failure as presentation of late-onset Pompe disease complicating the diagnostic process as a labyrinth: a case report

BackgroundAcute respiratory failure can be triggered by several causes, either of pulmonary or extra-pulmonary origin. Pompe disease, or type II glycogen storage disease, is a serious and often fatal disorder, due to a pathological accumulation of glycogen caused by a defective activiy of acid α-glucosidase (acid maltase), a lysosomal enzyme involved in glycogen degradation. The prevalence of the disease is estimated between 1 in 40,000 to 1 in 300,000 subjects.Case presentationThis case report describes a difficult diagnosis of late-onset Pompe disease (LOPD) in a 52 year old Caucasian woman with acute respiratory failure requiring orotracheal intubation and subsequent tracheostomy for long-term mechanical ventilation 24 h/day. Despite a complex diagnostic process including several blood tests, bronchoscopy with BAL, chest CT, brain NMR, electromyographies, only a muscle biopsy allowed to reach the correct diagnosis.DiscussionThe most frequent presentation of myopathies, including LOPD, is proximal limb muscle weakness. Respiratory related symptoms (dyspnea on effort, reduced physical capacity, recurrent infections, etc.) and respiratory failure are often evident in the later stages of the diseases, but they have been rarely described as the onset symptoms in LOPD. In our case, a third stage LOPD, the cooperation between pulmonologists and neurologists was crucial in reaching a correct diagnosis despite a very complex clinical scenario due to different confounding co-morbidities as potential causes of respiratory failure and an atypical presentation. In this patient, enzyme replacement therapy with infusion of alglucosidase alfa was associated with progressive reduction of ventilatory support to night hours, and recovery of autonomous walking.

Multidimensional evaluation in siblings affected by late onset Pompe disease

Late onset Pompe disease (LOPD) is an autosomal recessive neuromuscular disorder. Among the other symptoms patients are characterized by a reduction of bone mineral density (BMD) and muscle strength. Moreover there seems to be a cognitive involvement, which has not been well described yet. Therefore, the aim of this study was to assess bone, muscle, and cognitive impairments in all the members of a family affected by LOPD. We included siblings with same genotype (p.R40X/p.N882fs) affected by LOPD. These patients underwent an experimental evaluation protocol in order to evaluate: BMD, using the dual-energy X-ray absorptiometry (DXA); muscle strength, by Hand Grip Strength Test (HGS); level of independence, using the Functional Independence Measure (FIM); cognitive functions, using Trial Making Test A (TMT-A) and B (TMT-B) and the Stroop Color Test. Of 10 siblings with a diagnosis of LOPD, 7 (3 males and 4 females, mean aged 53.71 ± 6.05 years) had the same genotype (p.R40X/p.N882fs). Of these 7 patients, 4 (57.14%) had low BMD values (2 osteoporotic and 2 osteopenic) and hypovitaminosis D (< 30 ng/mL); two reported previous vertebral fragility fractures. The mean HGS was: 21.17 ± 0.76 kg in males and 14.50 ± 4.58 kg females. The mean FIM was 119.33 ± 2.31 in males and 121.00 ± 2.45 for females. Furthermore, in the neuropsychological evaluation, we found a mild attentional and executive deficit with a global cognitive framework within the normal ranges. In this study we found low BMD values in more than half of the examined cases, a reduction of muscle strength and a mild attentional and executive deficit. These results testify the necessity of a multidimensional assessment to better investigate all the characteristics of these patients.