Table 1.
Summary of patients with glycogenin-1 deficiency who were investigated in this study.
| Patient | Pt1 | Pt2 | Pt3 | Pt4 | Pt5 |
|---|---|---|---|---|---|
| Sex | M | F | M | M | M |
| Origin | Italy | Spain | Germany | New Zealand and UK | Sweden |
| Age at onset, y | 82 | 65 | 62 | 34 | Probably childhood |
| Initial symptoms | Progressive pain and weakness in upper left arm | Difficulties climbing stairs and walking | Difficulties climbing stairs and walking | Shortness of breath, chest pain on exertion, lethargy, and palpitations | Shortness of breath and upper arm weakness |
| Age at examination, y | 84 | 72 | 72 | 48 | 27 |
| Clinical features | Weakness in proximal and distal upper and lower limbs, partly asymmetric | Shoulder and hip girdle muscle weakness | Hip girdle and thigh muscle weakness and atrophy; milder asymmetric weakness of shoulder girdle and upper arm muscles | Cardiac failure. Heart transplantation at age 48 | Cardiac failure with reduced ejection fraction. Cardiac arrhythmias. Minor weakness in upper arms, neck flexion, and foot dorsiflexion |
| Cardiomyopathy | No | No | No | Yes | Yes |
| Muscle histopathology | Myopathy with α-amylase resistant,PAS-positive inclusions and nemaline rods. Increase in interstitial fibrous and fat tissue | Partially α-amylase resistant,PAS-positive inclusions | Partially α-amylase resistant, PAS-positive inclusions. Moderate increase in interstitial fibrous and fat tissue | Variability in fiber size and rare fibers with partially α-amylase resistant, PAS-positive inclusions | Smaller muscle fiber size than normal; glycogen deficiency |
| Heart histopathology | Not performed | Not performed | Not performed | PAS-positive inclusions in almost all cardiomyocytes, with partial removal by α-amylase | PAS-positive inclusions in almost all cardiomyocytes, with partial removal by α-amylase |
| DNA analysis | Homozygous c.2T > A | Homozygous c.46G > C | Compound heterozygous c.7G > C c.143 + 3G > C | Homozygous c.304G > C | Compound heterozygous c.248C > T c.487delG |
| Predicted protein change | Start codon mutation | p.Ala16Pro | p.Asp3Glufs*4 p.spl | p.Asp102His | p.Thr83Met p.Asp163Thrfs*5 |
| Previous report in which patient was described | (7) | Patient P4 (6) | Patient P5 (6) | (15) | (5) |
| Tissue investigated in this study | Skeletal muscle | Skeletal muscle | Skeletal muscle | Endomyocardial biopsy and heart explant | Endomyocardial biopsy |
Abbreviations: F, female; M, male; GYG1, NM_004130.3; PAS, periodic acid–Schiff; Pt, patient; UK, United Kingdom; y, years.