Endocrine Abstracts

Case History: A 64-year-old gentleman presented with progressive exertional breathlessness since 1 year. He had started noticing pigmentation in the eyes 2 years back, and gave a history of passing black coloured urine since childhood. He had never consulted a medical professional for the same. Examination revealed hyperpigmentation of both ears and conjunctivae, and an ejection systolic murmur (Grade V) at the aortic area, which radiated to both his carotids. A sample of his urine revealed the colour of his urine to be cola-coloured. Echocardiography confirmed valvular aortic stenosis with the pressure gradient across the aortic valve being 72 mm Hg, and the valve area being 0.8 cm². The gas chromatography-mass spectrometry analysis of his urine revealed that urinary levels of homogentisic acid were elevated, thus confirming the diagnosis of alkaptonuria. He refused surgery, hence, after a discussion between the patient, the treating cardiologist, and the cardiothoracic surgeon, a transcatheter aortic valve replacement (TAVR) was done by his cardiologist. Alkaptonuria, one of the first disorders in humans found to conform with the principles of Mendelian recessive inheritance¹, is a rare hereditary disorder in which deficiency of homogentisate 1,2 dioxygenase (HGD) (the enzyme predominantly produced by hepatocytes in the liver and within the kidney, and is responsible for the breakdown of HGA; an intermediate in the tyrosine degradation pathway) leads to urinary excretion of homogentisic acid in large amounts, which darkens on standing². Accumulation of oxidized homogentisic acid pigment in connective tissue (ochronosis) also occurs, namely in the sclerae of the eye, as well as the concha of the ear³. The disease may be picked in the patients when they are young owing to the peculiar colour of their urine, but may often be ignored until their latter years. Patients usually present with degenerative arthritis in the middle age. Degenerative cardiac disease, especially aortic stenosis as in this case, may also occur and is an important clinical problem in older patients⁴.

References

1. Mistry JB, Bukhari M & Taylor AM. Alkaptonuria. Rare Dis. 2013 1 e27475.

2. Ranganath LR & Jarvis JC. Gallaghe. Recent advances in management of alkaptonuria (invited review; best practice article) Journal of Clinical Pathology 2013 66 367–373.

3. Lodh M & Kerketta JA. Early diagnosis of co-existent ß-thalassemia and alkaptonuria. Indian J Hum Genet. 2013 19 259–261.

4. Phornphutkul C, Introne WJ & Perry MB, et al. Natural history of alkaptonuria. N Engl J Med 2002 347 2111–2121.