Wrong Diagnoses Prior to the Ultimate Diagnosis of Late-onset Pompe Disease: A Multicenter Experience
Dennis Huang1, Marie Wencel1, Suur Biliciler2, Yessar Hussain3, Shafeeq Ladha4, Andrew Heim5, Mazen Dimachkie5, Alan Pestronk6, Tahseen Mozaffar1
1University of California Irvine, 2University of Texas Health Science Center at Houston, 3Austin Neuromuscular Center, 4Barrow Neurological Institute, 5University of Kansas Medical Center, 6Washington University in Saint Louis - Neurology
Objective:
To provide further details on previous misdiagnoses in patients ultimately diagnosed with Late Onset Pompe Disease (LOPD). This abstract covers various misdiagnoses conferred prior to the ultimately delayed diagnosis of LOPD leading to delays in initiation of treatment.
Background:
Pompe Disease is an autosomal recessive glycogen storage disease, characterized by a skeletal myopathy and respiratory insufficiency, caused by deficiency of acid alpha-glucosidase (GAA), which leads to the accumulation of lysosomal glycogen. With emerging newborn screening data, the incidence of LOPD appears to be much higher than previously estimated and approximates that of more common inherited neuromuscular disorders, such as Myotonic Dystrophy (DM1) and Facioscapulohumeral Muscular Dystrophy (FSHD). However, most large neuromuscular clinics do not have as many LOPD patients as FSHD and DM1, suggesting that these patients are either misdiagnosed or that not all mutations in LOPD are fully penetrant. LOPD is a treatable condition and early diagnosis results in earlier initiation of life-saving enzyme replacement.
Design/Methods:
Case series compiled from 6 academic medical centers describing twenty-six patients who initially received an incorrect diagnosis but were ultimately diagnosed with LOPD.
Results:
Previous diagnoses included: limb-girdle muscular dystrophy, Oculopharyngeal Muscular Dystrophy, nonspecific muscular dystrophy, inflammatory myositis, liver disease which in some cases lead to multiple liver biopsies, bilateral phrenic nerve palsies, lumbosacral radiculopathy, and in one child primary respiratory failure. Average time from onset of symptoms to age of diagnosis when specific ages were available was 10 years.
Conclusions:
Pompe Disease is underrecognized and can be misdiagnosed as a variety of other conditions including muscular dystrophy, inflammatory myositis, or even hepatic disease. These misdiagnoses lead to delays in initiation of treatment and result in morbidity and mortality for patients. There is a need for education for physicians to recognize symptoms of LOPD and refer them accordingly to appropriate specialty centers.