Table 6:
Literature review
| Reference | No. Cases | Age | CK (IU/L) | AST | ALT | Radiologic findings | Physical examination | EMG/NCS | Neurological Complaints | Development | Muscle Biopsy |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Moses et al (1986)28 | 16 | age range 2–27 | Elevated in all subjects | Little or no weakness (n=11), weakness limiting from physical exercise (n=3, improved with age). | N=9. Mixed pattern (n=3), myopathy (n=6). All patients had numerous short, small amplitude MUPs, most prominent in proximal muscles. | Numerous fibers with subsarcolemmal deposits of PAS + material. | |||||
| Coleman (1992)29 | 13 (7 GSD IIIa, 3 IIIb, 3 IIId) | Mean 24.8 (4–57, median 17) | GSD IIIa: Patients <15 y (n=6) CK activity less than 500. Oldest men (n-2) CK > 1000. | Mild weakness on physical exam (n=4), moderate (n=4), severe (n=2). Three older patients: proximal and distal weakness with atrophy of intrinsic hand muscles and calf. | NCS: myopathic (n=7), decreased motor nerve conduction (n=2) | Walking delayed (n=3, 18 mo-3 years) | |||||
| Kiechl et al (1999)30 | 1 | 47-year-old female | Began at 401, declined to 95 | Muscle strength was 4+/5 (MRC scale) in deltoid and biceps, otherwise normal | Reduction in CMAPs in median and peroneal nerves, low-amplitude, polyphasic potentials in biceps, deltoid, and intercostal muscles. | Diffuse mild wasting of muscles. DTRs decreased bilaterally. | Moderate variation in fiber size without obvious fibrosis. | ||||
| Kiechl et al (1999)31 | 4 | Median 52.5, range (8 months-62 years) | Mean: 470.75 (239–810), median: 417 | Slow, progressive muscle wasting of calves, proximal limb, and trunk muscles | myopathic and neurogenic features with reduced nerve conduction velocity in n=2. | DTRs decreased in arms and absent in feet. | Walking delayed to 2 years | PAS positive vacuolar myopathy, cytoplasmic glycogen pools. | |||
| Hobson-Webb et al (2010)22 | GSD IIIa (n=11); GSDIIIb (n=1)) | Mean age 31.42 (range 5–55) | Mean max 1961 (n=11, range 216–9264) | Weakness in proximal lower extremities (n=1), proximal limbs and intrinsic hand muscles (n=2), proximal and distal limbs and intrinsic hand muscles (n=1). | EMG (n=8, abnormal n=6) Myopathic MUPs n=3, neuropathic MUPs in median n=1. |
Paresthesias in fingertips, feet, distal legs. Mild distal lower extremity numbness, forearm cramping. | Mild delay in developmental milestones. Decreased endurance. | ||||
| Wary et al (2010)26 | 18 | Mean age 30.44 (11–67 yrs) | Fatty replacement in muscles (n=15). Calf muscles most frequently impacted. | Weakness (n=3), proximal >distal weakness (n=9), distal > proximal weakness (n=5), no weakness (n=1; GSD IIIb). Exercise intolerance with fatiguability. |
Glycogen vacuolation slightly higher for type 1 fibers. | ||||||
| Gershen et al (2015)32 | 1 | 25 yo male | 3261 | 225 | 290 | Normal muscle bulk and tone, mild proximal limb muscle weakness worse in legs than arms, reflexes 1/4 throughout. | Moderate variation in muscle fiber size, focal increased endomysial fibrosis, chronic endomysial inflammation. | ||||
| Mogahed et al (2015)17 | 28 | Mean Age 6.6 (SD 3.1 yrs) | Elevated (n=21), | Elevated (n=24) | Elevated (n=23) | Normal muscle power (n=20), mild weakness (n=6). Exercise intolerance, difficulty climbing stairs (n=18). | Myopathic changes (n=17), 3 with associated axonopathy | Normal muscle tone and reflexes. | Delayed sitting, standing, and walking | ||
| Decostre (2016)25 | 18 GSDIIIa | Mean (SD) 32 (13)m median 32, range 13–56 | Hip flexion weakest Pinch strength (annual loss of 1.10%), Purdue Pegboard (1.49% annual decline), handgrip (loss of 1.84% annually) |
Plantar flexion contracture (n=14) | |||||||
| Herlin et al (2016)20 | 16 GSDIIIa | Mean Age 33 (17–52 yo) | Mean 4187 (346–9104) | Muscle fatty degeneration in posterior compartments of legs | Exercise Intolerance (n=4). Weakness proximal (n=3), distal (n=8, legs n=1, arms n=5, both n=2). Distal hand muscles wasting (n=3) | Myopathic MUPs (15/16), primarily in TA and FDI. | Distal paresthesias (n=1), Normal reflexes in all patients. |
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| Verbeek (2016)18 | 11 (GSD IIa children, GSDIII adults) | Children (n=5, median age 4; adults (n=6, a=4, b=2), median age 31y | Increased in 3/5 GSD IIIa children (median: 420, range: 128–981); 4/4 GSD IIIa adults (median 1249, range 1093–1823) | Children: high MUD prox>distal. Adult MUD higher than children, prox>distal. | Adults with GSDIII had muscle weakness of the shoulder abductors, elbow extensors, finger flexors, knee extensors, summed-arm and summed-proximal muscles | Normal EMG results with respect to sensory and motor conductance velocities and amplitudes. | 2/5 GSDIII children and 5/6 GSDIII adults experienced neuromuscular complains | ||||
| Decostre (2017)6 | 13 GSDIIIa | Last prospective visit mean 37 (SD12) | N= 12, mean at first visit 2456 (57–9170, SD 2539, median 1981), mean at last visit 2258 (SD 2518, median 855, range 263–7716) | N=13, mean at last visit 144 (42–298, SD 85, median 126) | Progressive impairment of finger dexterity, handgrip strength, and transfer mobility after age 30. | All but 1 patient had plantar flexion contracture | |||||
| Nazari et al (2018)33 | 5 | Mean age 36.6(18–51), median age 40 | Mean: 2367.2 (1033–3367) | Mean: 137.6 (70–221) | Symmetric weakness of proximal and distal muscles; mild hand and hip muscle weakness. | Low-amplitude, short-duration, polyphasic MUPs. NCS: axonal sensory motor polyneuropathy (n=2). | Chronic axonal sensorimotor polyneuropathy (n=2). | Developmental delay (n=3), two with delayed walking. | Multiple subsarcolemmal and cytoplasmic PAS + vacuoles. | ||
| Zhang (2018)34 | 4 (GSD IIIa) | Mean 21 y(range 14–32), median 19 | Mean: 2275 (range 1126–4000) | Mean: 138.5 (range 75–202). | Mean: 122 (range 78–199) | Mild T1 signal intensity in the long head of femoris and peroneus longus muscles (increased adipose content) | All patients had MUP in proximal limbs with negative NCS | ||||
| Chehida et al (2019)21 | 50 (GSD III) | last evaluation median age: 9.87 y (16 mo-41 y) | CK elevation noticed at median age of 2.6 years (0.33–35 years) | AST elevated, decreased with age. | Muscle weakness of limbs (66%), LE (31%) >UE (19%). Weakness distribution (proximal n=1, distal n=2, both n=17). | ENMG anomalies, in 62% of patients (myogenic pattern 42%, neurogenic 12%, mixed 18%). | DTR abnormalities of lower limbs (n=14, Achilles reflex), upper limbs (n=5). | Median age walking: 18 mo (12–30 mo), late walking 43%. | |||
| Tobaly et al (2019)9 | 15 (GSDIII) | Mean age 36 yrs (range 16–59) | T1-weighted MRI sequences: symmetrical fat replacement of muscle without severe atrophy. | Total MFM scores sensitive to age, specifically in patients > 30 yrs |
Compound Muscle Action Potential (CMAP), motor unit potential (MUP), Tibialis anterior (TA), First Dorsal Interosseous (FDI), Vastus Lateralis (VL), Vastus medialis (VM), Deep Tendon Reflexes (DTR), Nerve Conduction Studies (NCS).