Fig. 1

 A. CT angiography and coventional angiography images of patient-1 [CGL1; AGPAT2 homozygous p.R68X (c.202 C > T)]. 3D computed tomography reconstruction of lower abdomen and extremity arteries showing severe stenosis in the right common iliac artery, superficial femoral artery (SFA), and P1 segment of the popliteal artery (PA) (I). High pressure 5-mm drug-eluting balloon (DEB) angioplasty was performed to the P1 segment of the PA. High pressure plain old balloon angioplasty (POBA) followed with 6-mm self-expanding nitinol stent implantation and post dilatation with 6mm POBA was performed to the SFA. A 10-mm balloon-expandable bare metal stent was deployed to the right common iliac artery beginning from the orifice (II). The ulcer healed weeks after the revascularization procedure.

B. Patient-2 [CGL1; AGPAT2 homozygous IVS5-2 A > C (c.662-2 A > C)] had several episodes of diabetic foot ulcer (DFU). Here, her 6th episode is shown. Figure 1B (I) shows a deep infected predominantly neuropathic ulcer on the medial aspect of the right foot with a total infected area of 200 cm², disseminated osteomyelitis, and soft tissue abscess. Plain lateral foot radiogram (II) shows rocker-bottom foot deformity, gas in soft tissues associated with gas gangrene, disseminated osteolysis, bone deformation and destruction. T1-weighted axial MR images (III) show distal metatarsal bone marrow edema, joint inflammation and soft tissue edema. Postcontrast T1-weighted fat-saturated axial (IV) and coronal (V) MR images display diffuse contrast enhancement of bone marrow, and soft tissue edema which is compatible with ostomyelitis and cellulitis. A soft tissue abscess formation is shown. Wound culture identified several pathogens over time including Enterococcus spp., ESBL-producing Escherichia coli, and Candida albicans. The DFU did not heal despite broad-spectrum antibiotics including ampicillin-sulbactam plus ciprofloxacin (81 days), meropenem (17 days) and teicoplanin (31 days), aggressive debridement, predilatation with the plain old balloon angioplasty followed by DEB angioplasty to the right SFA, and vacuum assisted closure (VAC) therapy was performed. She underwent a below the knee amputation; however, she is still being treated for wound infection at the amputation site.

C. A grade 4 ulcer (8 × 4 cm) on the left big toe and first metatarsus, spreading to the neighboring forefoot areas which is complicated with osteomyelitis and necrosis [I; Patient-3: CGL1; AGPAT2 homozygous p.E229X (c.685G > T)]. Wound culture identified Streptococcus spp., and she received clindamycin and ciprofloxacin P.O. for 18 days. The vascular assessment identified left popliteal artery stenosis and above-the-knee amputation was performed. She also received VAC and hyperbaric oxygen post-amputation. She later developed a grade 1 neuropathic ulcer on the right big toe (II). She had accompanying onychomycosis. In the same period, she developed multiple bullae in her both hands located on the right third and left second and third fingers. These lesions healed with local wound care and antifungal treatment.

D. A necrotic forefoot ulcer covering the entire right big toe, index toe and middle toe (I; Patient-7: APL). The ulcer is complicated with osteomyelitis and necrosis. Infected tissue necrosis to the stump extending the suture line (II).

E. Bullous lesions on the plantar surfaces of toes (big, index, middle and fourth toes in the left foot; varying between 1 × 1 and 3 × 3 cm in size. [Patient-8: CGL1; AGPAT2 homozygous p.D180PfsX5 (c.538_539delGA)].

F. A large neuropathic ulcer (20 × 5 cm) predominantly affecting the dorsal aspect of the forefoot and midfoot (I) in patient-9 [FPLD2; LMNA heterozygous p.R482W (c.144 C > T)]. She received parenteral meropenem for 21 days followed by amoxicillin-clavulanic acid and ciprofloxacin P.O. for 6 months, and the ulcer healed. Later, she presented with another neuropathic ulcer that developed in her right big toe but widespread into her forefoot and even midfoot. The ulcer was further complicated with cellulitis, soft tissue abscess, osteomyelitis, and local gangrene. She was treated with parenteral piperacillin and tazobactam and linezolid (16 days) which was followed by linezolid monotherapy (P.O. for 14 days). She underwent a toe amputation but the ulcer has not healed yet despite wound care (II)