Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0392525 (nephrolithiasis)
 2,669 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Alkaptonuric ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review. 1593 60

Endogenous ochronosis or alkaptonuria is a rare, autosomal recessive disease of tyrosine metabolism that is caused by a deficiency of the enzyme homogentisic acid oxidase. The disease results in the accumulation and deposition of homogentisic acid in the cartilage, eyelids, forehead, cheeks, axillae, genital region, buccal mucosa, larynx, tympanic membranes, and tendons. The disease generally presents in adults with arthritis and skin abnormalities; occasionally, involvement of other organs may be seen. A 49-year-old man was referred to our clinic with verrucous lesions on his hands. On physical examination, caviar-like ochronotic papules were found around his eyes and the helix cartilage of his ears, and on the dorsa of both hands. There were brown macules on the sclera (Osler's sign). The patient had arthritis and nephrolithiasis, and a sample of his urine darkened upon standing. Histopathological examination showed deposition of ochronotic pigment. High-dose ascorbic acid was given, and the patient showed improvement on follow-up examination 6 months later.
 ...
PMID:Endogenous ochronosis. 2005 50