Alkaptonuric Ochronosis

Abstract

Alkaptonuria, with its sequel, ochronosis, is a rare disease, with an incidence of 1:125,000 to 1:1 million worldwide. Reported cases of ochronotic arthropathy and other orthopedic manifestations are mostly limited to a single family tree, and few cases have been reported. This study highlights 9 previously unreported patients with sporadic presentation and varied orthopedic manifestations of alkaptonuria. Patient age ranged from 34 to 50 years. One patient who had severe arthropathy of the right hip joint along with subcutaneous nodules over both knees and Achilles tendons underwent total hip replacement. Another patient had intramedullary calcification of the femur. An additional patient had associated caries of the spine at L3, L4, and L5, with resolution of symptoms after antitubercular chemotherapy. Another patient had associated features of hyperthyroidism, which was an incidental finding. A further patient had nonunion fracture of the neck of the femur and underwent total hip replacement. The remaining 4 patients had typical features of low backache and arthritis of the large joints. The parents were nonconsanguineous, and only 2 patients had affected siblings. The remaining 7 patients had sporadic nonfamilial presentation. Diagnosis was established by typical clinical and radiologic findings and biochemical analysis. At 2 years of follow-up, both patients who underwent total hip replacement were normal, with no radiologic signs of loosening or lysis. Clinicians need a high index of suspicion and awareness to make the diagnosis of ochronosis. The current study is unique because of presentation with subcutaneous nodules in 1 patient and associated caries of the spine in another patient.

Alkaptonuria: Spontaneous Achilles tendon rupture: Case report

“…[7] One of the biggest problems in the treatment of Achilles tendon rupture, which is a common pathology in orthopedic surgery, is to repair the ends of the torn tendon ends after the debridement and to return to the old strength without rerupture. [1] In our case, an adequate stability was achieved after debridement of the torn ends and the procedure of approximation and strengthening of the healthy tendon ends. However, the rehabilitation process included the conventional treatment plan for Achilles tendon rupture, which involved firstly slightly-flexed plaster cast, then gradual neutralization, partial load-bearing, and full range of motion.…”

“…The mild antioxidant nature of ascorbic acid helps to retard the conversion of homogentisate to the polymeric material which is deposited in the cartilaginous tissues. [1,3] In human and mouse experiments, it was observed that nitisinone changed the urinary HGA extraction significantly. Although it is recommended to use this drug in tyrosinemia type 1, there is no significant information for its use in ocronosis patients.…”

Septic arthritis in ochronosis’ patient

“…First description of Alkaptonuria was done by Garrod in 1908, that also recognized it to follow classic Mendelian recessive inheritance. 1 The genetic defect is mapped to the HGD gene and more than 90 different mutations have been identified to date. 2 Alkaptonuria is caused by homogentisic acid oxidase enzyme deficiency, that results in high homogentisic acid levels.…”

Misdiagnosis of alkaptonuria in an elderly patient

“…To date, more than 90 mutations of the HGD gene have been described, reflecting the disorder's clinical variability 2 . The inabitily to metabolise tyrosine and phenylalanine leads to HGA accumulation in the blood; the amount excreted in the urine turns dark brown or black on oxygenation or alkalinization 6,7 .This typical urine colour occurs early in the disease course but may not be noticed; fresh urine often seem normal and it may take several hours after voiding for the colour changes to occur. Homogentisic acid products resemble melanin and are deposited in the collagen, particularly the cartilage; the resulting tissue colour (ochre) gives the name ochronosis to the process 8 .…”

“…There is a predominance of men relative to women 2:1 10 . Less common manifestations include renal, urethral, and prostatic calculi, cardiovascular abnormalities and valvular disease 7,11,12 .…”