Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

Abstract

Alkaptonuria is a rare autosomal recessive disorder of metabolism caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in collagenous structures. It is characterized by homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and arthropathy of large joints. Less common manifestations include cardiovascular abnormalities, renal, urethral and prostate calculi. Bone fractures are unusual in ochronosis.In this report, we describe a woman, 69 years of age, with a history of dark urine since childhood and progressive pigmentation of the skin, sclera, and auricular cartilages. She had severe arthropathy requiring total joint replacement in both of her knees and right hip. She also had severe aortic stenosis requiring valve replacement, and asymptomatic nephrolithiasis. She presented with a low trauma fracture of the distal femur despite two years of alendroate therapy.We review the etiology, pathogenesis, clinical presentation, diagnosis and treatment of alkaptonuric ochronosis. Early detection is important for prevention and treatment of multiple systems. Nitisinone, a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces production and urinary excretion of homogentisic acid; however, the long-term efficacy and side effects of such therapy are unknown. Identifying the gene for alkaptonuria offers the potential for a new therapeutic approach (replacement therapy with a recombinant enzyme) in the treatment of alkaptonuric ochronosis.

Cerebro-spinal and renal ochronosis: A rare case report

“…Cardiac manifestations include aortic or mitral valvulitis, formation of atherosclerotic plaques containing cholesterol and fat, calcification of the coronary arteries and eventually myocardial infarction (11). However, in our case no cardiac manifestations were detected.…”

A Previously Undiagnosed Case of Alkaptonuria: A Case Report

“…This occurs due to the deposition of ochronotic pigment in the intervertebral discs and articular cartilage of the large joints. [13] Ochronotic spondyloarthropathy resembles ankylosing spondylitis (AS) in its damage to the spine and large joints; however, it differs in that it spares the sacroiliac joints and does not have the annular ossification, syndesmosis, or bamboo spine that are associated with AKU. [14] In addition, AS is also indicated by the appearance of thin, vertical syndesmophytes, severe involvement of the apophyseal facet joints, and erosion and fusion of the sacroiliac joints.…”

Alkaptonuria

“…Aortic valve stenosis is a frequent finding, often requiring surgical replacement. 23 It may be that mechanical forces play a key role in mediating ochronosis given that there appears to be little pigmentation in the venous component of the circulation compared with the arterial side. 17 Interestingly, while HGD expression and HGA metabolism occur in the liver, there are no reports to demonstrate that these tissues-along with those of the pancreas, gastrointestinal, lymphoreticular, or endocrine organs-develop ochronosis.…”

“…21 Organs affected are: large joints, cardiovascular system, kidney, skin, and glands. 4,7,[22][23][24] Other manifestations include: renal, prostate, gall bladder, and salivary gland stones, ruptures of tendons and ligaments, osteopenia, and fractures. 4,[25][26][27] Cardiac manifestations of the disease are not uncommon.…”