Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review

A 43-year-old man living in southern Jordan presented to our clinic in March 2019 with sudden onset of left Achilles tendon pain with no history of prior trauma. He had developed progressive low back and knee pain for the previous 5 years, which was managed using nonsteroidal anti-inflammatory drugs. He was diagnosed with alkaptonuria 10 years earlier (urine analysis and biochemical testing confirmed the HGA-uria at the time of diagnosis). The patient had discoloration of his teeth, ear pinna, and sclera of the eye (Figure 1), and his urine has been dark since childhood (Figures 2C, D). His sister and brother have been also diagnosed with alkaptonuria, and his parents are related (consanguineous marriage). Genetic analysis identified a homozygous missense variant c.365C>T lies in exon 6 of HGD resulting in the substitution of the amino acid alanine (Ala) with valine (Val) Ala122Val (SNP ID rs544956641) [17] (Figures 2A, B) as deposited in the HGD mutation database [4].

Figure 1

Figure 2

Physical examination revealed a palpable defect over the left Achilles tendon at its insertion. Absence of plantarflexion was observed using a Simmonds–Thompson test. Lumbosacral computed tomography (CT) showed diffuse degenerative changes of the spine (Figure 3). Magnetic resonance imaging (MRI) revealed that the tendinous insertion of the Achilles tendon into the calcaneus tuberosity was completely disrupted with retraction of the proximal part (Figure 4). Surgical exploration through the medial incision to the Achilles tendon down to its insertion site revealed a complete disruption of the tendon at its attachment to calcaneus with fragile, black deposited frayed edges (Figure 5A). The black pigmentation was extensive and reaching the calcaneal tuberosity, extending about 7 cm from the insertion. The excision involved the entire pigmented segment (Figure 5B) and specimens of the fragmented tendon were sent for histopathology with the suspicion of ochronosis. Tendon advancement was not possible due to the large gap created after the excision (>5 cm). A decision was taken to graft the flexor hallucis longus (FHL) tendon (Figures 5C–E). The posterior aspect of the calcaneus was involved in the deposition as well; so, it was challenging to find a healthy area to implant the graft. A suitable area 2 cm anterior to the insertion was prepared after curettage to assure a healthy vascularized bed for the graft. The FHL tendon was forfeited at the Henry knot, and the graft was pulled up through the original incision. With appropriate orientation of the fibers of the FHL tendon, the graft was secured with a conventional screw into the calcaneus. The graft was sufficiently long enough to be sutured over the proximal stump of the Achilles using an absorbable polyglactin 910 suture (Vicryl; Ethicon/Johnson and Johnson). Intraoperatively, a stable plantar and dorsiflexion of the ankle was achieved (Figure 6). Histopathological examination of the resected portion of the tendon revealed a thick fibrosed tendinous tissue with chronic inflammation and focal pigment deposition consistent with the classical features usually seen in alkaptonuria.

Figure 3

Figure 4

Figure 5

Figure 6

The patient was discharged from the hospital 2 days after surgery with a cast fitted in a slight plantar flexion. At 3 weeks, the cast was changed to a walking cast with the ankle in a neutral position. At 6 weeks, the cast was removed and the patient started gentle ankle motion physiotherapy. At 10 weeks postoperatively, the patient presented to the clinic walking with the aid of one crutch. Physical examination revealed 0–20° of plantarflexion and 0–15° of dorsiflexion. At 6 months’ follow-up, our patient presented to the clinic walking without any aid and physical examination revealed a satisfactory range of motion. Written informed consent was obtained from the patient to publish the present case report and associated images, and the CARE reporting guidelines were used when writing the report [18].

Ochronotic osteoarthropathy is the first systemic manifestation in patients with alkaptonuria, starting in their 20s or 30s. The ochronotic pigment deposited in the bone matrix impairs the bone mineralization process and activates bone resorption [19, 20]. Additionally, the deposition of the pigmented polymers of HGA in the connective tissues affects the structural integrity of collagen and increases the possibility of tendons to rupture due to their high collagen content [21]. Spontaneous and nontraumatic Achilles tendon rupture due to ochronosis is uncommon and only a few cases from various countries have been reported with their successful surgical treatment. There is no standard method for repairing the tear because the torn ends can be ragged due to extensive degeneration and are not ideal for neat suturing, and most notably, there is a gap length after the excision of the frayed ends. Therefore, several surgical techniques have been utilized for the management of ochronotic Achilles tendon rupture [22], such as direct repair, V-Y advancement, tendon transfer, the Lindholm double facial flap technique, and the Bosworth technique after the removal of the discolored part of the tendon [10, 12, 14, 15, 23, 24].

In a case in a 46-year-old Sudanese man, the pigmentation was restricted to a few millimeters from the ruptured surface and the tendon was repaired directly using Vicryl [13]. By contrast, a gap measuring approximately 5 cm in a 39-year-old Jordanian man was repaired using an inverted V-Y technique to restore the length of the tendon [10]. Baca et al. reported a gap of 6 cm after debridement and the tendon was repaired using the Lindholm double facial flap technique [12]. However, in a case in a 50-year-old Turkish man with a complete Achilles tendon rupture from its insertion to the calcaneus, approximately 5 mm of the discolored Achilles tendon was excised and no gap was present after the tendon repair. After debridement, two titanium anchors were fixed at the attachment point on the calcaneus [23].

Here, we report a case of spontaneous rupture of the Achilles tendon at its insertion due to alkaptonuria treated using FHL tendon transfer. The extensive degeneration of the tendon necessitated the removal of a significant portion of the ochronotic tendon, leaving a gap similar to that observed in chronic Achilles tendon rupture. To date, there is still no standard treatment of chronic Achilles tendon rupture with large gaps [25]. However, evaluating the presence or absence of the Achilles tendon stump at the calcaneus and the gap length of rupture gives some indication of the repair technique [26]. When the gap is from 1 cm to 2 cm: usually end-to-end repair with or without tenodesis augmentation. When 2–5 cm: usually V-Y advancement with or without tenodesis augmentation. For >5 cm: autograft or allograft tendon transfer or reconstruction [27]. The FHL tendon is a strong, long tendon, and allows bridging of large gaps [28]. The FHL muscle has the same function as the gastrocnemius and soleus; it has the same axis of moving with the Achilles tendon and does not disrupt the normal muscle balance of the ankle [29]. Accordingly, the FHL tendon has been reported to be the most successful for chronic Achilles reconstruction and reconstruction of the degenerated tendon, and it is recommended for all defects >2 cm [30, 31]. In the present case, FHL tendon transfer was considered appropriate for surgical reconstruction with the surgical goal of allowing the patient to regain as much strength as possible. The patient experienced uncomplicated healing with satisfactory functional results. To our knowledge, only one previous case report describes performing long flexor tendon transposition for Achilles tendon rupture due to alkaptonuria [24].

In Achilles tendon repairs, absorbable suture material is associated with a lower incidence of complications compared with nonabsorbable sutures made of material such as polypropylene, which tend to induce foreign-body reaction [32, 33]. Mohammed et al. described the use of Vicryl as an absorbable suture material used to reconstruct a tendon after the resection of ruptured ends [13]. However, some authors reported the use of titanium suture anchors to reattach the tendon to the calcaneus instead of a primary suture fixation to additionally support and reinforce the tendon [23, 34]. Ngcelwane et al. reported the use of a running nylon material to suture the paratenon and to reconnect the debrided ends of an ochronotic tendon [35]. Several studies showed that the Achilles tendon healing is promoted by an intact paratenon, the membrane that envelopes the tendon [36]. Asynchronous bilateral rupture of the Achilles tendon has also been reported in some patients with ochronosis [13, 16, 34]. Alkaptonuria is a systemic disease and some cases reported indicate that the incidence of multiple sequential ruptures of various tendons secondary to ochronosis is possible over time [35, 37]. Consequently, prophylactic therapy for alkaptonuric ochronosis is needed to avoid subsequent tendon ruptures. Physicians suggest a lower protein intake particularly of tyrosine-rich food and to take ascorbic acid (vitamin C) at a dose of 0.5–1.0 g/day [12, 35, 38]. Additionally, physical and occupational therapies may be adopted to maintain the flexibility and strength of the muscles and tendons [24]. Nonsteroidal anti-inflammatory drugs for symptomatic treatment as well as glucosamine and chondroitin sulfate supplements, which are considered to slow the degeneration of joint cartilage, have been recommended [23]. The current approach is to use a low dose of nitisinone, which has a role in delaying the disease progression by inhibiting HGA formation and subsequent accumulation in tissues [39, 40]. Recently, 2 clinical trials, SONIA 1 and SONIA 2 approved the efficacy and safety of nitisinone as a therapy for alkaptonuria [41, 42].

The surgical treatment of an Achilles tendon rupture with a large gap is a challenge for most orthopedic surgeons. Ochronotic tendinopathy and ochronotic osteoporosis in patients with alkaptonuria make the treatment even more challenging. Although the technique is technically challenging, this case report provides evidence that FHL tendon transfer is an effective technique for the treatment of spontaneous rupture of a severely ochronotic tendon in a patient with alkaptonuria. Such extensive ochronotic involvement of the Achilles tendon of alkaptonuria has been reported rarely.