Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
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In alkaptonuric ochronosis, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid in the body. Associated renal failure is rare and usually occurs in the later stages of the disease. We report a 19-yr-old girl who presented initially with severe renal failure, without family or past history of illness. There was no significant proteinuria or hematuria. No clinical evidence of pigmentation such as skin and subcutaneous cartilages was noted. However, pigment deposits were identified in the renal biopsy specimens obtained within a week after admission and another after a month. Two months later the peritoneal dialysis fluid and skin progressively darkened, suggesting ochronosis. This was confirmed by the detection of homogentisic acid in the serum and urine. The patient expired in renal failure. Renal biopsy tissues showed diffuse chronic tubulo-interstitial disease characterized by widespread tubular atrophy, interstitial fibrosis, and a moderate degree of inflammation. Many tubular cells contained brown, coarsely granular ochronotic pigment (OP) and a few pigment casts were in the lumina. Similar deposits were also in the interstitium and within histiocytes. Ultrastructural studies of the glomeruli revealed small sparse OP deposits in the visceral and parietal epithelial cells, mesangial cells, and rare extracellular and basement membrane deposits. The tubulointerstitial changes were varied: atrophy and dilatation of tubules, varying degrees of lysosomal OP and degeneration of tubular cells, casts containing OP with crystalline material, histiocytes distended with OP, and free interstitial pigment deposition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alkaptonuria and renal failure: a case report and review of the literature. 149 52

Alkaptonuria is a rare disease of phenylalanine, aromatic amino acids, and tyrosine metabolism. Because of a genetic deficiency of the enzyme homogentisic acid oxidase, an accumulation of homogentisic acid causes ochronotic pigment deposition. The most common clinical manifestations are arthropathy, urinary calculi and discoloration, cutaneous and cartilaginous pigmentation, and cardiac valvular disease. Arthropathy and aortic stenosis are the most debilitating manifestations of the disease. A case of alkaptonuric aortic stenosis is described. A 75-year-old woman with a history of alkaptonuria presented in the emergency department with complaints of progressive dyspnea. Upon examination, the patient was hypertensive, tachypneic, and tachycardic with premature ventricular contractions. She had pitting edema of the lower extremities and complaints of generalized weakness. Chest x-rays revealed congestive heart failure and pulmonary edema. Diuretics were administered, and a continuous nitroglycerin infusion was initiated in the emergency department. The patient was admitted for further evaluation. The patient's respiratory status continued to decline. She was intubated endotracheally 1 day after admission. Subsequent cardiac evaluation revealed an ejection fraction of 35%, severe aortic stenosis, mild coronary artery disease, ischemic cardiomyopathy, and anteroapical akinesis. A dobutamine infusion was instituted for persistent hypotension, and renal dose dopamine was initiated for oliguric renal failure. The patient underwent an emergency operation for an aortic valve replacement with a Dacron patch 10 days after admission. Cardiopulmonary bypass and mild hypothermia were used during the procedure. The patient's hemodynamic status remained tenuous throughout the procedure. Although the first attempt to wean off cardiopulmonary bypass failed, the second attempt was successful with the aid of an intra-aortic balloon pump, inotropic support, and atrioventricular pacing. These measures were maintained during transport to the surgical intensive care unit. In the intensive care unit, the patient did not have an audible blood pressure or a palpable pulse without the support of the intra-aortic balloon pump and atrioventricular pacing. Coarse atrial fibrillation was the underlying electrocardiogram rhythm in the absence of atrioventricular pacing. Sodium bicarbonate was given without improvement. After discussion with the family, all life support measures were discontinued. The patient died 10 minutes after her arrival in the intensive care unit. Alkaptonuria's pathogenesis is manifested as both local and systemic in nature. Collagen vascular diseases share a similar pattern of multisystem involvement. Despite the negative outcome for the patient described, valuable insight can be obtained by studying this case and noting the anesthetic considerations specific to collagen vascular diseases in general.
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PMID:Alkaptonuric aortic stenosis: a case report. 1048 88

In alkaptonuria, homogentisate 1,2-dioxygenase deficiency causes tissue accumulation of homogentisic acid (HGA), followed by signs and symptoms of ochronosis. These include massive urinary excretion of HGA, arthritis and joint destruction, pigmentation of cartilage and connective tissue, and cardiac valve deterioration. We describe a 46-year-old man with alkaptonuria and diabetic renal failure whose plasma HGA concentration was twice that of any other alkaptonuria patient, and whose ochronosis progressed much more rapidly than that of his two alkaptonuric siblings. After renal transplantation, the plasma HGA normalized, and the daily urinary excretion of HGA decreased by 2-3g. This case illustrates the critical role of renal tubular secretion in eliminating HGA from the body, and suggests that renal transplantation in a uremic patient not only restores HGA excretion, but may also provide homogentisate 1,2-dioxygenase activity for the metabolism of HGA.
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PMID:Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation. 1235 41

In alkaptonuria, the absence of homogentisic acid oxidase (HGO) results in the accumulation of homogentisic acid (HGA) in the body. Associated renal failure is rare and usually occurs in the later stages of the disease. We report a 33-year-old male who presented, initially, with renal failure, but no past history of illness. He had pigmentation of sclerae and ear helices, intervertebral disk calcifications and mild mitral insufficiency. His disease was confirmed by HGA detection in the urine. As size and thickness of renal parenchyma seen on ultrasonography were normal, renal biopsy was performed and it showed glomerular sclerosis, diffuse tubular atrophy and interstitial fibrosis with inflammation. Wall thickening of small arteries and pigment deposits were identified in some kidney tissue elements. He progressed to end-stage renal disease despite supportive therapy.
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PMID:Alkaptonuria and renal failure: a case report. 1536 68

Alkaptonuria, a rare inborn error of tyrosine metabolism, characterized by the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid in the body. Associated renal failure and cerebral infarction is rare and usually occurs in the later stages of the disease. We report a 55-year-old male who presented, initially with features of stroke and degenerative arthritis. He had pigmentation of sclerae, darkening of urine on long standing, abnormal renal profile, degenerative arthritis and cerebral infarction. Alkaptonuria was suspected and biochemical tests confirmed mild renal impairment, homogentisic acid in urine and homogentisic acid crystal was detected cytologically in urine sediment. Such a case of Alkaptonuric ochronosis with cerebrovascular and renal complications have been rarely reported in the previous literature.
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PMID:Cerebro-spinal and renal ochronosis: A rare case report. 2310 12