Alkaptonuria

Introduction

Alkaptonuria is a rare metabolic disorder first described by Garrod.[1] The worldwide incidence in the population is 1:250000.[2] The disease is notably frequent in Czechoslovakia in which the incidence approaches 1:25000.[3] There are very few cases reported from India. It is characterised by deposition of oxidised homogentisic acid in fibrous and cartilaginous tissues, which manifests clinically as of dark urine (homogentisic aciduria), distinctive cutaneous pigmentation (ochronosis) and arthritis. [Figure - 1] Arthropathy may cause disabilities but the life expectancy is usually normal.

Case Report

A 50- year- old female, resident of Himachal Pradesh presented with the complaint of backache,pain in the hip,knee and shoulder joints, and inability to walk without support. There was history of the urine turing dark on standing since childhood There were no systemic complaints.There was no history of any drug intake. Family history was not contributory. On examination, black spots were seen bilaterally over the sclerae between the limbus and lateral canthus. Dark discoloration was seen on the index fingers and pinnae bilaterally. Oral mucosa was normal. The patient had a stooping posture and a short stepping gait. Examination of the spine revealed tenderness in the lumbar region and the movements were restricted in all directions. All the movements were decreased in the hip joints and shoulder joint. Bilateral rupture of the tendo-achilles was present. Chest expansion was within normal limits. Urine examination showed the presence of homogentisic acid. Radiological examination of the spine revealed marked osteoporosis, narrowing of disc space and calcification of the disc. Calcification was also seen around the knee joints.

Discussion

Alkaptonuria inherited as an autosomal recessive condition is characterised by the deficiency of homogentisic acid oxidase in the kidneys and liver. Recently, alkaptonuria gene was assigned to human chromosome 3q 21-q 23.[4] This leads to accumulation of homogentisic acid, an intermediate metabolite of phenylalanine and tyrosine catabolism.[5] Ochronosis occurs because of the deposition of a melanin-like brownish black pigment, derived from the oxidised product of homogentisic acid in the connective tissues and cartilage. The only manifestation may become apparent as early as the third decade and may be the presenting complaint.[6] Cutaneous manifestations in the form of ochronosis appear in the fourth decade.The earliest signs may include pigmentation and thickening of the ear cartilage. The extensor tendons on the knuckles show a distinctive pigmentation. Mucosae and nails may also be discolored. Ochronotic arthropathy occurs last of all which is heralded by pain, stiffness and some limitation of motion of the hips, knees and shoulders. Ankylosis of the lumbosacral spine is a common late manifestation.

Diagnosis in the present case was made by the presence of the triad of degenerative arthritis, ochronotic pigmentation and urine which turns black upon alkalisation.