Quantitative Evaluation of Upright Posture by X-Ray and 3D Stereophotogrammetry With an Original Marker Placement Protocol in Late Onset Pompe Disease.

Abstract Background: Late Onset Pompe Disease (LOPD) is an autosomal recessive muscular disorder characterized by prevailing weakness of trunk and pelvic girdle muscles that causes ventilatory insufficiency and postural abnormalities. The most common myopathy phenotype described clinically in LOPD is the Limb Girdle and Diaphragmatic Pattern; spinal deformities, as hyperlordosis, hyperkyphosis and scoliosis diagnosed by x-Ray exam, have been reported in about a third of LOPD patients. The non-specific clinic onset, the similarity of the LOPD phenotypes with other myopathies, inter-individual heterogeneity and the lack of any disease hallmark, make early diagnosis challenging and, if enzyme replacement therapy does not begin timely, about 60% of patients develops severe motor and ventilatory disabilities.Aim of our study was to quantitatively assess the upright posture in a sibship of LOPD adults by x-Ray(xR) and 3D Stereophotogrammetry (St), considered the gold standard to measure spinal angles and whole-body posture respectively, in order to better identify specific alterations more likely to be present in a homogeneous group.Results: Statistical analysis of St parameters showed a larger ankle, knee, elbow, dorsal, S2-C7, heel-S2-C7, heel-S2-nasion angles and a lower sagittal vertical axis (SVA) than healthy controls. Moreover, xR analysis highlighted a lower occipito-cervical, C2-C7 cervical and Cobb dorsal angles, and a trend to lower lumbar lordosis and SVA compared to normal values. Pearson’s coefficient analysis was carried on in order to evaluate the correlation between xR and St sagittal spino-pelvic parameters and significant correlation was found in dorsal and lumbar angles calculated using xR markers placed on spiny apophysis, xR centre of vertebral bodies, Cobb method and St markers. Conclusions: This is the first study that quantitatively assesses standing whole-body alignment and postural abnormalities in LOPD. These postural alterations are not easily detectable during clinical examination and might be useful to early identify LOPD patients and to facilitate differential diagnosis with other proximal myopathies. Moreover, our St-mks placement protocol showed high reliability to assess any sagittal angles and, being non-invasive as compared to xR, is advisable to investigate and monitor the course of the disease and the response to treatment.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22073625 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3625

Author(s):

Filomena Napolitano ◽

Giorgia Bruno ◽

Chiara Terracciano ◽

Giuseppina Franzese ◽

Nicole Piera Palomba ◽

...

Keyword(s):

Pompe Disease ◽

Rare Variants ◽

Clinical Symptoms ◽

Late Onset ◽

Respiratory Muscles ◽

Autosomal Recessive Disorder ◽

Compound Heterozygous ◽

Enzyme Replacement ◽

Whole Exome ◽

Clinical Pictures

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

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A 4-year follow-up study of 24 patients with late onset Pompe disease treated with alglucosidase alfa enzyme replacement therapy at a single centre

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2014.12.252 ◽

2015 ◽

Vol 114 (2) ◽

pp. S111

Author(s):

Karolina M. Stepien ◽

Jane Whitby ◽

Mark Roberts ◽

Reena Sharma

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Single Centre ◽

Enzyme Replacement ◽

Follow Up Study ◽

Alglucosidase Alfa

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Reduced Efficacy of Enzyme Replacement Therapy in a Child with Late-Onset Pompe Disease

Pediatrics & Therapeutics ◽

10.4172/2161-0665.1000290 ◽

2016 ◽

Vol 06 (02) ◽

Cited By ~ 1

Author(s):

Satoru Takahashi ◽

Ryosuke Tanaka

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Enzyme Replacement

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

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2018.176 ◽

2018 ◽

Vol 13 ◽

Author(s):

Francesco Menzella ◽

Luca Codeluppi ◽

Mirco Lusuardi ◽

Carla Galeone ◽

Franco Valzania ◽

...

Keyword(s):

Case Report ◽

Respiratory Failure ◽

Acute Respiratory Failure ◽

Pompe Disease ◽

Late Onset ◽

Correct Diagnosis ◽

Ventilatory Support ◽

Diagnostic Process ◽

Caucasian Woman ◽

Enzyme Replacement

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.

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