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

Abstract

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.

Is early detection of late-onset Pompe disease a pneumologist’s affair? A lesson from an Italian screening study

“…In our study, both of the two patients found to have LOPD has displayed respiratory and neurologic symptoms for more than 1 year, but they were detected only during an episode of acute respiratory failure with the need of RHDCU admission. This latency of the diagnosis may seem too high, but it is much less than other literature reports [8, 16, 17]. In line with our results, Kishnani et al [19] recently reported that patients with early respiratory involvement can be diagnosed sooner than those presenting with only muscular symptoms and/or hyperCPKaemia.…”

“…Acute respiratory failure requiring mechanical ventilation in Intensive Care Units (ICU) or in Respiratory High Dependency Care Units (RHDCU) may be the first clinical presentation of the disease [7]. However, LOPD with a prevalent respiratory derangement is not easily and promptly identified during an acute respiratory failure episode because the critical illness itself doesn’t allow a clearly diagnostic electromyographic study [8].…”

Benefit of 5 years of enzyme replacement therapy in advanced late onset Pompe. A case report of misdiagnosis for three decades with acute respiratory failure at presentation

“…This revealed the two pathogenic variants already described. One variant results in a premature codon and due to nonsense mediated decay results in haploinsufficiency [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] ]. This variant has been reported repeatedly in the literature with Pompe's patients including LOPD.…”

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

“…Recessive mutations in this gene are linked to congenital myasthenic syndrome (CMS17), a severe neuromuscular disorder associated to respiratory failure [ 43 ]. Respiratory related symptoms (dyspnoea on effort, reduced physical capacity and recurrent infections) and respiratory failure are often evident in the later stages of LOPD [ 45 ]. The two rare and deleterious LRP4 variants identified only in this patient alter the highly conserved residues laying in important domains of the protein ( Figure 4 ).…”