scholarly journals Tetraparesis and sensorimotor axonal polyneuropathy due to co-occurrence of Pompe disease and hereditary ATTR amyloidosis

2020 ◽  
Author(s):  
Milan Zimmermann ◽  
Natalie Deininger ◽  
Sophia Willikens ◽  
Tobias B. Haack ◽  
Kathrin Grundmann-Hauser ◽  
...  
Keyword(s):  
Clinical Features ◽  
Muscle Weakness ◽  
Pompe Disease ◽  
Late Onset ◽  
Single Gene ◽  
Lower Limbs ◽  
Sensory Loss ◽  
Motor Neuropathy ◽  
Transthyretin Amyloidosis ◽  
Attr Amyloidosis

Abstract Introduction/aims Hereditary transthyretin amyloidosis with polyneuropathy (hATTRPN) is an autosomal dominant multi-organ disorder manifesting in the third to fifth decade with the key clinical features of distal and painful sensory loss of the lower limbs and autonomic dysregulation. Motor neuropathy and cardiomyopathy evolve in the course of the disease. Pompe disease is an autosomal recessive disease leading to decreased levels of lysosomal enzyme acid α-glucosidase and proximal muscle weakness. We report the clinical features and diagnostic workup in the rare case of a patient with ATTR amyloidosis and late-onset Pompe disease, both genetically confirmed. Methods We performed a detailed clinical assessment, exome sequencing, and biochemical measurements. Results The patient presented with a distal, painful hypaesthesia of both legs, a cardiomyopathy, and a muscle weakness in the form of a girdle-type pattern of the arms and legs at the beginning and a spreading to distal muscle groups in the course of disease. Discussion This study highlights the importance of searching for co-occurrence of rare monogenetic neuromuscular diseases, especially in cases in which all clinical features can be readily explained by a single gene defect.

scholarly journals Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease

2016 ◽  
Vol 17 (10) ◽  
pp. 1735 ◽  
Author(s):  
Matthias Boentert ◽  
Hélène Prigent ◽  
Katalin Várdi ◽  
Harrison Jones ◽  
Uwe Mellies ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Pompe Disease ◽  
Respiratory Muscle ◽  
Late Onset ◽  
Respiratory Muscle Weakness ◽  
Diagnosis And Management ◽  
Practical Recommendations

P336A descriptive analysis of patients with wild-type ATTR cardiomyopathy from the transthyretin amyloidosis outcomes survey

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Garcia-Pavia ◽  
M Grogan ◽  
A Dispenzieri ◽  
R Mundayat ◽  
L Amass ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Cardiac Disease ◽  
The United States ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Motor Neuropathy ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Ventricular Ejection Fraction ◽  
Attr Amyloidosis

Abstract Introduction Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disorder caused by the deposition of amyloid fibrils composed of misfolded transthyretin (TTR). ATTR amyloidosis may arise from mutations in TTR or from aggregation of wild-type TTR (ATTRwt). ATTR amyloidosis with predominantly symptoms of cardiomyopathy (ATTR-CM) includes both hereditary and wild-type forms of the disease. Purpose To describe clinical history and disease presentation in a large population of patients with wild-type ATTR-CM from the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic patients with TTR mutations. Methods Data from ATTRwt patients were extracted from THAOS (cut-off date: January 16, 2019) and demographic and clinical characteristics reported using descriptive statistics. Results There were 758 ATTRwt patients in THAOS (95% male). The majority of patients (69.3%) were in the United States, with the remainder in Italy (11.1%), Germany (7.3%), Spain (5.3%), and other countries (7.1%). Most patients (86.3%) were Caucasian, with 3.3% being of African Descent and 3.1% being of other races/ethnicities (7.4% missing data). The median (10–90th percentile) age at symptom onset was 69.7 (54.0–81.3) years and the median (10–90th percentile) time from symptom onset to diagnosis was 3.9 (0.1–17.8) years. Median (10–90th percentile) age at enrollment in THAOS was 76.4 (67.2–85.2) years. Nearly all subjects had either a cardiac (59.6%) or mixed cardiac and neurologic (36.5%) phenotype. At enrollment, 97.1% (577 of 594 patients assessed) had an abnormal ECG, with the prevalence of low voltage being 20.8% (115 of 552) and prevalence of left-ventricular hypertrophy being 2.1% (16 of 758). Atrial fibrillation was documented in 55% of patients (208 of 378). The mean (standard deviation [SD]) left-ventricular septum thickness was 17.5 (3.5) mm (n=505; 94.9% with thickness >12 mm) and mean (SD) left-ventricular ejection fraction (LVEF) was 48.3% (13.2) (n=511; 48.0% with LVEF <50.0%). Other signs and symptoms at enrollment were compatible with a sensory neuropathy in 54.2% of patients, autonomic neuropathy in 33.5% of patients, and motor neuropathy in 29.1% of patients. Gastrointestinal symptoms related to ATTR amyloidosis were present in 10.4% of patients. Conclusions Although patients with wild-type ATTR-CM tend to be older Caucasian men with a mostly cardiac disease phenotype, the clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype. Our findings show that ATTRwt should not be considered an exclusively cardiac disease and there is a need for both cardiologic and neurologic assessment of these patients. Further study is needed to determine if the non-cardiac manifestations are due to amyloidosis or more common causes in this older population. Acknowledgement/Funding This study was sponsored by Pfizer.

The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: A multicenter study

2016 ◽  
Vol 26 (11) ◽  
pp. 796-800 ◽  
Author(s):  
Olcay Ünver ◽  
Nilüfer Eldeş Hacıfazlıoğlu ◽  
Elif Karatoprak ◽  
Ayfer Sakarya Güneş ◽  
Güneş Sağer ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Multicenter Study ◽  
Pompe Disease ◽  
Pediatric Patients ◽  
Late Onset ◽  
Girdle Muscle

Clinical features of late-onset Pompe disease: A prospective cohort study

2008 ◽  
Vol 38 (4) ◽  
pp. 1236-1245 ◽  
Author(s):  
John H.J. Wokke ◽  
Diana M. Escolar ◽  
Alan Pestronk ◽  
Kenneth M. Jaffe ◽  
Gregory T. Carter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Clinical Features ◽  
Prospective Cohort Study ◽  
Pompe Disease ◽  
Prospective Cohort ◽  
Late Onset

Clinical Features of Late-onset Ankylosing Spondylitis: Comparison with Early-onset Disease

2012 ◽  
Vol 39 (5) ◽  
pp. 1008-1012 ◽  
Author(s):  
CARLOS MONTILLA ◽  
JAVIER DEL PINO-MONTES ◽  
EDUARDO COLLANTES-ESTEVEZ ◽  
PILAR FONT ◽  
PEDRO ZARCO ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Clinical Features ◽  
Early Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Young Patients ◽  
Lower Limbs ◽  
Joint Disease ◽  
Control Group ◽  
Onset Group

Objective.Ankylosing spondylitis (AS) is generally observed in young patients but can occur later in life or in persons ≥ 50 years of age. Our objective was to characterize the clinical features of late-onset AS in a large multicenter national cohort.Methods.We studied late-onset AS in the National Registry of Spondyloarthritis of the Spanish Society of Rheumatology (REGISPONSER database) cohort (n = 1257), of whom 3.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years.Results.There were no differences between late-onset and early-onset AS according to sex and family history of spondyloarthropathies. Patients in the late-onset group more often showed involvement of the cervical spine (22.7% vs 9.7%; p = 0.03) and arthritis of the upper (13.6% vs 3.0%; p = 0.002) and lower limbs (27.3% vs 15.2%; p = 0.03) as first manifestations than did patients in the early-onset group. A higher percentage of mixed forms (axial and peripheral joint disease) during the course of the disease was also recorded in the late-onset group (50% vs 24%; p = 0.0001).Conclusion.Our study suggests that age at onset of AS affects the patients’ presenting clinical form. Arthritis of the upper limbs requires a differential diagnosis with other conditions frequent in patients over 50 years of age, such as rheumatoid arthritis or crystal-induced arthropathy.

scholarly journals Variable clinical features and genotype-phenotype correlations in 18 patients with late-onset Pompe disease

2019 ◽  
Vol 7 (13) ◽  
pp. 276-276 ◽  
Author(s):  
Jousef Alandy-dy ◽  
Marie Wencel ◽  
Kathy Hall ◽  
Julie Simon ◽  
Yanjun Chen ◽  
...  
Keyword(s):  
Clinical Features ◽  
Pompe Disease ◽  
Late Onset

Selective screening of late-onset Pompe disease (LOPD) in patients with non-diagnostic muscle biopsies

2019 ◽  
Vol 72 (7) ◽  
pp. 468-472
Author(s):  
Marija Meznaric ◽  
Ksenija Fumic ◽  
Lea Leonardis
Keyword(s):  
Muscle Weakness ◽  
Pompe Disease ◽  
Late Onset ◽  
Tissue Bank ◽  
Study Results ◽  
French Speaking ◽  
Ventilatory Insufficiency ◽  
Low Prevalence ◽  
The University ◽  
Muscle Biopsies

AimsAs of 2016, there were five patients with Pompe in Slovenia (two infantile, one childhood and two adult onset) with a prevalence of 1:400 000; however, the prevalence of late-onset Pompe disease (LOPD) in some other countries means this ratio could be an underestimate. Since an LOPD muscle biopsy could be unspecific or even normal, the purpose of this study is to assess the prevalence of LOPD in patients with non-diagnostic muscle biopsies.MethodsSix hundred biopsies were recorded at the Neuromuscular Tissue Bank of the University of Ljubljana for the period 2004–2014. All adult patients with non-diagnostic muscle biopsies were invited to the National Slovenian Neuromuscular Centre for dried blood spot testing for LOPD.ResultsA total of 90 patients (56% of those invited) responded. No patient with LOPD was found. A total of 49 patients (54%) had fixed muscle weakness, 31 (34%) had mild symptoms and no weakness and 10 (11%) had asymptomatic hyperCKemia. Ventilatory insufficiency associated with proximal muscle weakness was found in two patients (2%). No patients exhibited vacuolar myopathy, globular accumulations of glycogen or regions of increased acid phosphatase activity within the sarcoplasm.ConclusionsThe study results do not support the hypothesis that LOPD is underestimated in Slovenian patients with non-diagnostic muscle biopsies; this could be consistent with the fact that LOPD is of low prevalence in Slovenia, as is the case in the populations of Finland, French-speaking Belgium, west Sweden and west Denmark.

P3.57 Clinical features, disease progression and prognostic factors of muscle weakness in adults with Pompe disease

2011 ◽  
Vol 21 (9-10) ◽  
pp. 699-700
Author(s):  
N.A.M. van der Beek ◽  
J.M. de Vries ◽  
M.L.C. Hagemans ◽  
W.C.J. Hop ◽  
M.A. Kroos ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Disease Progression ◽  
Clinical Features ◽  
Muscle Weakness ◽  
Pompe Disease

scholarly journals A Clinical Case of the Hereditary Transthyretin Amyloidosis

2021 ◽  
Vol 11 (3) ◽  
pp. 229-240
Author(s):  
E. V. Reznik ◽  
T. L. Nguyen ◽  
S. V. Borisovskaya ◽  
L. V. Brylev ◽  
A. V. Zhelnin ◽  
...  
Keyword(s):  
Polarized Light ◽  
Left Ventricular ◽  
Lower Limbs ◽  
Unknown Etiology ◽  
Wall Thickening ◽  
Fatty Tissue ◽  
Transthyretin Amyloidosis ◽  
Sensorimotor Polyneuropathy ◽  
Attr Amyloidosis ◽  
Wide Range

Introduction: Transthyretin (ATTR) amyloidosis is a severe rare disease with wide range of characters without specific symptoms including the damage to the peripheral nervous system and cardiac involvement. Case report: A 60-year-old female patient represented with weakness and paresthesia in the distal parts of the lower limbs, impeding walking for 2 years. Initially, symptoms were considered as a manifestation of degenerative stenosis of the lumbar spine, decompressive laminectomy was performed but the symptoms after surgical treatment persisted. Based on data from clinical and electroneuromyographic examinations, axonal sensorimotor polyneuropathy was diagnosed. Genetic testing of the patient, her elder sister, son and daughter using the Sanger sequencing method detected a variant of the nucleotide sequence in the fourth exon of the transthyretin gene (Chr18: 29178562, rs148538950, NM_000371.3: c.G368A: p. Arg123His) in the heterozygous state. A subcutaneous fatty tissue biopsy of abdominal wall with a Congo red stain and polarized light examination revealed amyloid microdeposits, grade CR 1+ (minimal deposits), confirmed the diagnosis of familial ATTR-amyloidosis. Echocardiography revealed concentric left ventricular wall thickening with normal end diastolic size and volume, preserved ejection fraction, left atrial enlargement, pulmonary hypertension and type 1 diastolic dysfunction. Specific anti-amyloid therapy — tafamidis was prescribed. Conclusion: In patients with peripheral polyneuropathy and left ventricular hypertrophy of unknown etiology, a complex examination is necessary for the timely detection and treatment of amyloid polyneuropathy and cardiomyopathy.

scholarly journals Pompe disease: case report in siblings

2021 ◽  
Author(s):  
Eduarda Pereira de Barros ◽  
Fábio Lima Baggio ◽  
Bruna Giaretta Ventorin ◽  
Amanda Raminelli Morceli ◽  
Diogo Fraxino de Almeida
Keyword(s):  
Muscle Strength ◽  
Disease Progression ◽  
Muscle Weakness ◽  
Pompe Disease ◽  
Lower Limbs ◽  
Apnea Hypopnea Index ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Mild Phenotype ◽  
Disease Case

Introduction: Pompe disease (PD) affects lysosomal digestion due to absence or low action of the enzyme acid α-glucosidase (GAA), with accumulation of glycogen, causing overflow of enzymes and autophagy, which affects striated muscle. PD is divided into infantile, juvenile, and adult clinical forms, with severity determined by amount of residual GAA activity. Case: P1) 45-year-old man admitted with acute respiratory failure (RF), starts mechanical ventilation. History of weakness, dyspnea, dysphagia. He had decreased proximal muscle strength at lower limbs (LL). Sequencing of GAA gene: autosomal recessive deficiency of two variants. Apnea-hypopnea-index (AHI):10.5. GAA enzyme replacement therapy (ERT) was requested. Judicially denied by disease progression. P2) 40-year-old man presented with loss of muscle strength at LL for 15 years, associated with snoring, daytime somnolence. Brother with similar complaints. He had proximal muscle weakness at LL. Positive genetic panel for PD. AHI:23.5. Judicially released ERT treatment and reported improvement. Discussion: Adult form of PD manifests itself with mild phenotype, with presence of residual GAA activity, which causes different clinical expressions. Main manifestations are symmetric proximal muscle weakness in LL and Gowers’ sign. Frequent death cause in late form is RF, which occurs early, unlike other neuromuscular diseases. In Brazil, PD is underdiagnosed, with approximately 2500 cases. Treatment is performed with Myozyme®, an ERT, not available in SUS, which makes treatment difficult. Conclusion: PD is a serious condition, with high underdiagnosis because of its similarity to other myopathies, which allows disease progression. Furthermore, the variability of GAA mutations allows for distinct phenotypes

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