Sequential spontaneous compartment syndrome in multiple limbs in a young adult with GYG1 gene mutation

Abstract

Compartment syndrome is a surgical emergency requiring immediate intervention. Majority of compartment syndromes are associated with trauma or surgery. Spontaneous compartment syndrome in multiple limbs is rare and alternative diagnosis should be sought. We report a young adult man who developed compartment syndrome in all four limbs sequentially over 4 years. On further evaluation, he was found to have a gene mutation in exon 3 of GYG1 gene. Spontaneous compartment syndrome in patients with GYG1 gene mutation does not appear to have been previously recognised. Although a direct causality cannot be confidently drawn, this gene is involved in muscle energy utilisation and is known to cause metabolic defect. Acute compartment syndrome, once diagnosed, warrants emergency surgical decompression. The subsequent management of spontaneous compartment syndrome demands a thorough medical assessment to identify any underlying metabolic or genetic predisposition.

Background

Acute compartment syndrome (ACS) is a surgical emergency requiring immediate decompression of the affected compartment in order to prevent debilitating complications.¹ Majority of ACS are associated with trauma (69% associated with fractures and 23.2% due to soft tissue injury).² However, a small percentage of ACS is related to malignancy, medications or anticoagulant therapy.³

We report a case of spontaneous compartment syndrome (SCS) that occurred sequentially in all four limbs in a patient with underlying GYG1 gene mutation and highlight the importance of interspecialty collaboration in its management.

Case presentation

We report a previously healthy young adult man who developed compartment syndrome in all four limbs on different occasions over a period of 4 years. He first developed compartment syndrome in the right forearm following a mild blunt trauma to the forearm sustained as a result of a fall. He described the fall as low impact from sitting height only. In the subsequent evening, he developed excruciating forearm pain and paraesthesia in the hand, hence presenting to the accident and emergency department. A clinical diagnosis of ACS in the right forearm was made and he underwent emergency fasciotomy the same night. At the time of surgery, there was necrosis in the posterior compartment, involving the extensor carpi ulnaris muscle belly, which needed debridement. A week later, the volar forearm wound required coverage with split thickness skin graft (SSG) (figure 1).

Figure 1.

Clinical picture of the right forearm following split thickness skin grafting.

Four months later, he re-presented with spontaneous-onset extreme pain localised to the posterior aspect of his right proximal forearm. The previous wounds had healed well and the patient was in the process of undergoing scar revision to the right forearm scar by means of serial excision. He had no neurological deficit. Due to the unusual presentation, he underwent an MRI that showed non-specific oedema in the posterior compartment. However, due to the intractable pain, he underwent re-exploration of the posterior compartment and some haematoma was decompressed. This provided him with significant pain relief. Subsequent vascular and haematological consults did not reveal any obvious underlying cause. The posterior wound was managed with vacuum-assisted dressing initially, followed by SSG. He recovered well with intact hand and wrist functions.

Three years later, he developed spontaneous left forearm compartment syndrome without antecedent trauma. He noticed pain, swelling and bruising of his left forearm while he was playing with his children. Similarly, he was treated with emergency fasciotomy and delayed SSG.

Due to the unusual presentation, he was referred to a neurologist with special interest in muscle pathology. Following genetic analysis, he was found to have a single gene mutation in exon 3 of GYG1 gene.

Six months later, he developed SCS of the left leg following exertion. On presentation, creatine kinase was 506 U/L. Compartment pressures were: anterior 47 mm/Hg; lateral 34 mm/Hg and posterior 22 mm/Hg. Two-incision, four-compartment fasciotomy was done. The anterior compartment was tight and tibialis anterior appeared dusky, which improved following decompression. Similar but less severe findings were found in the lateral compartment, and healthy-looking muscles were encountered in the posterior compartment (figure 2).

Figure 2.

Intraoperative picture of the left leg fasciotomy.

Seven months later, he presented with left arm compartment syndrome before re-admission 5 months later with right thigh and leg compartment syndromes. In the following month, he presented with left thigh compartment syndrome and quickly followed by right arm compartment syndrome 15 days later. All of the above incidences were managed with emergency fasciotomy accordingly.

Outcome and follow-up

By 4 years from the first presentation, the patient has undergone fasciotomy in all four limbs. Apart from scars, he has preserved movements and sensation in his limbs. He remains under the joint care of the surgeons and neurologist.

Discussion

SCS is rare.⁴ Recurrent compartment syndromes are even scarcer. Several case reports have postulated potential role of underlying metabolic or connective tissue disorders in the causation of SCS,^5–7 which appears to be more prevalent in patients with McArdle disease.^7–10 In the latter group, there appears to be a risk of precipitating compartment syndrome following ischaemic work test,^{8 9} and some may be related to exertion.^{7 10}

GYG1 gene is responsible for production of glycogenin, which is an essential protein in the synthesis of glycogen. Mutations of the gene (both homozygous and compound heterozygous) have been found in a rare type of glycogen storage disease.^11–13 Muscle weakness and easy fatigability have been described in patients suffering from this condition.

Testoni et al revealed interesting findings in their attempt to study the effects of lack of glycogenin on muscle function. They used genetically modified mice for detailed description of changes in muscle function. The structural changes they observed in muscle of the GYG1 deficient mice were similar to that described in humans affected with GYG1 mutations. They concluded that GYG1 deficiency results in accumulation of glycogen in skeletal muscle. However, when this glycogen is preferentially mobilised by muscle fibres that otherwise rely on oxidative metabolism, it translates to decreased resistance to prolonged low-intensity activity.¹¹ Conversely in McArdle disease, the inability to use stored glycogen and the resultant muscle ischaemia is postulated to be the cause of ensuing compartment syndrome.^{7 14}

To the best of our knowledge, there has been no established association between SCS and GYG1 gene mutation. Although direct causation has not been confirmed, due to the absence of any other factors and the known role of GYG1 gene in glycogen storage and utilisation affecting muscle function,¹¹ we postulate that the specific gene mutation has led to a predilection for SCS in our patient. The true pathogenesis remains to be elucidated.

We maintain that ACS is a clinical diagnosis and its treatment remains emergency fasciotomy. The instant relief of pain following decompression supported the indication of surgery.

Learning points.

• Acute compartment syndrome (ACS), once diagnosed, should always be managed with urgent surgical decompression.

• After the immediate treatment, spontaneous compartment syndrome (SCS) demands a thorough medical assessment in order to identify any underlying metabolic or genetic predisposition.

• GYG1 gene mutation is known to affect glycogen storage and utilisation affecting muscle function; hence, we postulate that the specific gene mutation has led to a predilection for SCS in our patient.

• Patients with SCS with an underlying metabolic or genetic predisposition should be educated of the potential risk for repeat episodes and remain vigilant for the signs of ACS.