Musculoskeletal Manifestations of Alkaptonuria: A Case-Based Review of Literature

Alkaptonuria is a rare metabolic disorder caused by a mutation in the homogentisate 1,2 dioxygenase (HGD) gene, which encodes the HGD enzyme. It is inherited in an autosomal recessive pattern. This leads to the accumulation of homogentisic acid (HGA) and benzoquinone acetic acid (BQA), which is an oxidised product of HGA. Both these compounds form polymerised deposits, which cause bluish black discolouration of the cartilage. They also cause inflammation, degeneration and calcification of ligaments, large joints, tendons and intervertebral discs. A fragmented cartilage forms, which attaches to the synovial membrane and causes subsequent degeneration and fibrosis, leading to ochronotic arthropathy. Both HGA and BQA are deposited in the bone and impair bone mineralisation, which leads to osteopenia and osteoporosis. We report a case of a 63-year-old gentleman with type 2 diabetes mellitus who presented with a history of chronic backache and acute urinary retention for one day. The patient also gave a history of urine turning dark on standing. Clinical examination revealed blackish sclera, kyphoscoliosis, and deformity of the distal interphalangeal joints of the hand. CT scan of the abdomen revealed multiple calculi within the prostatic urethra and the bulbar urethra, which explained the acute urinary retention. X-ray of the cervical spine showed narrowing of intervertebral spaces and straightening. X-ray of the dorso-lumbar spine showed kyphoscoliosis, calcification of intervertebral discs, subchondral sclerosis and disc space narrowing. X-ray of bilateral knee joints showed multiple osteophytes with joint space reduction and features of severe osteoarthritis of the knee. CT scan of the dorso-lumbar spine showed dorso-lumbar scoliosis of the vertebra, extensive ankylosis, diffuse osteopenia, disc space narrowing, multiple intervertebral disc space calcification and osteophytes involving the entire vertebrae. Urine HGA assay was found to be elevated (1161 mmol/L, normal < 1), which was diagnostic of alkaptonuria. The patient later underwent percutaneous cystolithotripsy. Following the procedure, blackish stones were retrieved, suggestive of alkapton bodies. Given the advanced stage of musculoskeletal manifestations, the prognosis was poor, and the patient was started on physiotherapy along with analgesics to help with mobility. Early identification of ochronotic arthropathy is imperative to slow the progression of the disease, to reduce morbidity, to improve the quality of life and to facilitate surgical intervention when necessary. We have reviewed the literature to summarise the musculoskeletal manifestations, radiological findings in alkaptonuria and the treatments that are available currently to treat alkaptonuria.