The recommended guidelines for treating Pompe disease (PD) are directed towards a wide range of healthcare providers. Treatment is primarily provided by neuromuscular experts, metabolic disease specialists, and biochemical geneticists. It is important that healthcare providers are able to distinguish and recognize patients suffering from PD. Diagnostic confirmation is critical, as PD can lead to a diagnostic dilemma due to its rarity and nonspecific phenotypic features. Differential diagnosis in terms of infantile- and late-onset PD should be considered. A follow-up check is required after confirmation of the diagnosis. Close follow-up is recommended for patients diagnosed with infantile PD. Follow-up every 6 months is recommended for patients diagnosed with late-onset PD.¹
Diagnostic Guideline for Late-Onset Pompe Disease
Diagnosing late-onset PD (LOPD) is quite difficult due to its clinical resemblance to other neuromuscular disorders. Timely and accurate diagnosis is critical based upon clinical parameters. As per guidelines based on clinical presentation and diagnostic criteria, physical examination shows proximal and distal weakness, and the pelvic girdle is affected to a greater degree than the shoulder girdle. Abdominal muscle and diaphragm weakness is noted in the early stages of the disease. Paraspinal muscle atrophy, scapuloperoneal weakness, and scapular winging are clinical manifestations of LOPD. The patient may also exhibit facial weakness or ptosis (unilateral or bilateral). Clinical myotonia is absent but paraspinal muscle shows electrophysiological myotonia. Patients diagnosed with LOPD may also suffer from nutritional deficiencies due to inadequate intake of vitamins, minerals, calories, and protein, which can lead to the endogenous breakdown of protein. Swallowing dysfunction may also be noted on videofluoroscopic swallowing assessment. Non-specific serum creatine kinase (CK) can be elevated in patients with LOPD. There may be increased muscle membrane irritability and myotonia as per myopathic potentials indicated in needle electromyography (EMG) studies.²
Criteria for Starting Enzyme Replacement Therapy (ERT)
Confirmed diagnosis for LOPD is critical prior to initiating enzyme replacement therapy (ERT). However, the start criteria for ERT may vary. As per stricter guidelines, only symptomatic patients may qualify for ERT. Other recommendations suggest that patients with specific signs such as elevated CK or abnormal muscle magnetic resonance imaging (MRI) may require ERT. Elevated CK levels can confirm a diagnosis of LOPD. The Pompe Disease Burden Scale (PDBS) divides PD into 4 major disease stages (I- IV), and it represents the spectrum of ERT starting criteria for LOPD. Patients diagnosed with LOPD on the basis of an affected sibling or through newborn screening who exhibit no signs or symptoms are included in PDBS I. Patients with muscle biopsy findings, CK elevation, or MRI findings are included in PDBS II, even with minimal respiratory or skeletal muscle dysfunction. PDBS III patients have symptoms and are divided into ambulatory patients requiring invasive ventilation, termed as category "A," and non-ambulatory patients with/without mechanical ventilation, termed as category "B." It should be noted that non-invasive ventilation does not play a role in starting ERT. PDBS IV includes severely affected patients with no residual muscle function.³
Management Guidelines for Infantile-Onset Pompe Disease
As per recommended guidelines, patients diagnosed with infantile-onset PD (IOPD) should be offered ERT every other week with a dosage equivalent to 20 mg/kg. Cross-reactive immunologic (CRIM) status needs to be determined prior to commencing ERT. The treatment plan should include a clinical trial of immune tolerance induction (ITI). Patients diagnosed with IOPD should be assessed by pediatric experts. Upon diagnosis, patients with IOPD should undergo respiratory assessment, and respiratory support should be provided as necessary. Infants diagnosed with IOPD require a sufficient intake of nutrients for adequate growth, hence, swallowing difficulties should be evaluated. ERT should be conducted for ambulatory IOPD patients with non-invasive ventilation.⁴
Physical Examination Guidelines for Adult and Juvenile Pompe Disease
The physical examination focuses primarily on muscular and respiratory symptoms for adult and juvenile PD. Pain and fatigue are commonly reported symptoms. Patients with PD may also demonstrate diaphragm weakness along with limb or axial muscle weakness. Patients with muscle fatigue or those who are asymptomatic may demonstrate morning headache and/or narcolepsy with myotonic paroxysm discharges on EMG. They may show compensatory rotation of the body when rising from the ground. MRI findings may show muscle atrophy with abnormalities in fat suppression in the posterior thigh, paravertebral, or abdominal muscles. Cardiac arrhythmias may be associated with skeletal muscle weakness as well. Idiopathic stroke with middle cerebral artery aneurysms and loss of rigidity of aortic compliance with hypertension may also be noted. Moreover, patients suffering from rigid spine syndrome, post-pubertal adolescent scoliosis, or adult idiopathic scoliosis are covered in adult and juvenile PD recommended guidelines.⁵
Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8(5):267-288. doi:10.1097/01.gim.0000218152.87434.f3
Cupler EJ, Berger KI, Leshner RT, et al.; AANEM Consensus Committee on Late-onset Pompe Disease. Consensus treatment recommendations for late‐onset Pompe disease. Muscle Nerve. 2012;45(3):319-333.
Hundsberger T, Schoser B, Leupold D, Rösler KM, Putora PM. Comparison of recent pivotal recommendations for the diagnosis and treatment of late-onset Pompe disease using diagnostic nodes—the Pompe disease burden scale. J Neurol. 2019;266(8):2010-2017. doi:10.1007/s00415-019-09373-2
Tarnopolsky M, Katzberg H, Petrof BJ, et al. Pompe disease: diagnosis and management. Evidence-based guidelines from a Canadian expert panel. Can J Neurol Sci. 2016;43(4):472-485. doi:10.1017/cjn.2016.37
Llerena JC Jr, Nascimento OJ, Oliveira ASB, et al. Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease. Arq Neuropsiquiatr. 2016;74(2):166-176. doi:10.1590/0004-282X20150194
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