Wilson's disease (a case report).
Wilson's disease is a rare familial disorder inherited as an autosomal recessive trait, being characterised by excessive accumulation of copper in the body particularly the liver, brain, cornea and kidney. We report below a case with some uncommon but well documented features of the disease.
P. S. , a 24 year old trader, was admitted with the history of difficulty in walking and painful movements of the limbs for 5 years; these had progressively worsened over the past 3 years. He was apparently well 5 years earlier, when he developed jaundice which persisted for 4 months. Jaundice was not preceded by anorexia, nausea, vomiting nor was it accompanied by pain in the right hypochondrium, haematemesis, diarrhoea, pruritis or a bleeding tendency. His sensorium had remained normal during the episode of jaundice. He recovered from that illness but noticed that he had difficulty in going up and coming down a staircase and in getting up from the squatting position. At the same time, he noticed difficulty in raising his arms up and in holding objects above the head. There had been no distal muscle weakness in the upper or the lower limbs. He could walk with support for the first 6 months of his illness but later, had required crutches. He was bedridden for 6 months prior to admission. All movements had been painful from the outset and more so over the past 3 years. He also had generalized aches and pains which were aggravated by coughing, sneezing and palpation. He initially responded partially to analgesics but for the past 6 months analgesics had been ineffective. His previous bone X-rays had shown generalised demineralisation with Milkman fractures of the left superior pubic ramus and neck of the left femur [Fig. 1] and these had improved with vitamin D and calcium supplements. The bone pain and muscle weakness, however, did not respond to this treatment and had actually grown worse. At that stage, he was referred to us for investigation.
On enquiry, there was no history suggestive of cranial nerve, sensory or bladder dysfunction; there was also no history of syphilis, diabetes, hypertension, convulsions, trauma, addiction to alcohol or tobacco. The patient denied having been treated with corticosteroids.
There was no history of consanguinity between the parents but one of his maternal cousins had suffered from similar illness and was treated with penicillamine for a short time before he died. The patient was 123 cms in height and weighed 52 kg. There was no pallor, jaundice, clubbing, cyanosis or peripheral lymphadenopathy. There was no parotid enlargement, palmer erythema, gynaecomastia, testicular atrophy or spider naevi. The patient had Kayser Fleisher rings; this was confirmed by slit-lamp examination. He had a sunflower cataract in both eyes. There were no azure lunulae. The skull and the spine were normal. A neurological examination showed weakness and wasting of muscles acting on the shoulder and hip joints and brisk deep reflexes. The plantar responses were flexor. There were no extrapyramidal signs nor any mental changes.
There was no abnormality in the heart, lungs or abdomen.
Haemoglobin level, total and differential W.B.C. count, serum cholesterol, creatinine, urea nitrogen, bilirubin, alkaline phosphatase, total proteins, albumin and globulin were all within normal limits. The corrected creatinine clearance was 60% of normal. Serum calcium levels were 10, 10.8 and 10.3 mg.% respectively on three occasions and serum inorganic phosphorus levels were 5.2, 6.0 and 3.0 m.% respectively on these three occasions. Prothrombin time was 18 seconds. Urine showed no abnormality.
The serum copper was 67 and 60/ug.% respectively on two consecutive days whereas the serum ceruloplasmin was 2.5 and 2.0 mg.% respectively on these two consecutive days. The urinary copper excretion on two occasions was 1060 ug and 120 ug per 24 hours respectively. The 24 hour urine calcium and phosphorus excretion was 160 mg and 400 mg respectively. There was evidence of aminoaciduria with excess of alanine and threonine. The short acid lead test (Wrong and Davies) showed a failure of acidification.
The patient refused permission for a liver biopsy.
A skeletal survey, during the present admission showed generalised demineralisation without any Milkman's fracture or subperiosteal bone cysts.
A diagnosis of Wilson's disease presenting with renal tubular acidosis and osteomalacic osteodystrophy was made and the patient was advised to take d-penicillamine 0.5 gm four times a day along with Shohl's citrate mixture. He took d-pencillamine for a period of 5 months and discontinued the same as he failed to obtain symptomatic relief from bone pains and weakness. He was persuaded to restart penicillamine, which he continued for a period of six months. Even at this length of time the patient failed to get relief from his symptoms and therefore discontinued the drug. He failed to attend for follow up thereafter.
The uncommon features of Wilson's disease in our patient include a sunflower cataract, osseomuscular and renal manifestations.
The sunflower cataract, or the Sonnenblumenkatarakt has been reported occasionally and is due to deposition of copper in the lens. Similar cataracts are known to occur following the intra-ocular localisation of a foreign body containing copper.
The osseomuscular manifestations.,  encountered in this patient were those of renal rickets namely osteomalacia, osteoporosis and spontaneous fractures. These initially responded to vitamin D and calcium supplements, but were subsequently refractory to treatment thus supporting the work of Dastur et al and Joshua.
The osseomuscular syndrome of Wilson's disease seems to be peculiar to the Indian subcontinent as 13 out of 17 cases so far reported come from India.,  Several mechanisms have been implicated in the pathogenesis of osseomuscular manifestations of Wilson's disease. They are: (a) it is a genetic variant of Wilson's disease, (b) it is secondary to renal tubular acidosis, (c) requires prolonged immobilisation on account of disability and finally (d) exhibit hepatic dysfunction.
The renal abnormalities that were present in our patient were aminoaciduria, renal tubular acidosis (type 2) and a reduced creatinine clearance. The latter two could well contribute to the genesis of the osseomuscular syndrome. Treatment with penicillamine was unsuccessful but patients of Wilson's disease with renal manifestations are known not to respond well to penicillamine.
We wish to thank the Dean, Seth G.S. Medical College and K.E.M. Hospital, Bombay, for permission to publish the above case report.