Hypoparathyroidism in a case of Wilson's disease: Rare association of a rare disorder.

Sir,

Wilson's disease, popularly known as hepatolenticular degeneration, is a disorder of copper metabolism in which there is a deficiency of copper transporting protein as a result of which excess copper is deposited at abnormal places. Liver is the primary site of involvement and eyes and brain are the other most consistently involved organs. However in a metabolic disorder like this, involvement of other organs yet unexplored and cannot be denied. We report a case of Wilson's disease with all known typical features, but one atypical finding that was resistant hypocalcemia due to hypoparathyroidism.

A 16-year-old boy presented with dystonias of limbs and orofacial region. He also showed features of tetany and carpopedal spasm [Figure 1]. His facial expression, extrapyramidal features and presence of Kayser- Fleischer rings around the cornea led us to make a diagnosis of Wilson's disease which was confirmed by laboratory investigations [Figure 2]. His serum calcium total and ionic (6.8 and 0.06 mg/dl respectively) and serum magnesium (1.29 mg/dl) levels were low. Serum phosphate level was high (7 mg/dl) and 24 hour urinary calcium level was low. Renal functions and routine urine analysis were normal. We started therapy with intravenous calcium gluconate and intramuscular magnesium which had a short-lasting effect on his tetany, and never provided consistent relief. When persistent therapy with intravenous calcium failed to restore serum calcium levels to normal even after several days, and tetany recurred, a circulating intact parathyroid hormone measurement was done which was minimally low (5.5 ng/l). Later, he was continued on magnesium, calcium and vitamin D replacement and his tetany started improving by the time he was discharged. Patient was treated with D penicillamine and zinc for his primary disorder.

Figure 1

Carpopedal spasm

Figure 2

MRI brain (T2 weighted) showing hyper intensities in bilateral basal ganglia

Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues like liver and brain, resulting in neurological or psychiatric symptoms and liver disease.[1] It is treated with medication that reduces copper absorption or removes excess copper from the body, but occasionally liver transplant is required.

The disease presents itself as a multisystem disorder. Various medical conditions have been linked with Wilsons disease like Kayser- Fleischer rings around cornea which occur in 66% of diagnosed cases.[1] It's presence specifically suggests the diagnosis. Sunflower cataracts can also be present.

It's rare association are renal tubular acidosis (causing loss of calcium phosphate and amino acids in urine), nephrocalcinosis and cardiovascular involvement in form of cardiomyopathy and arrhythmias. Infertility and habitual abortion may also occur.

Association of hypoparathyroidism with Wilson's disease causing hypocalcemia has been reported only twice in the existing literature.[23] Wilson's disease is among the rarest causes of hypoparathyroidism and the cause is essentially the destruction of parathyroid glands due to deposition of copper.[2] We were not aware of this association till our patient showed signs of resistant hypocalcemia in the form of recurrent tetanic spasms.

Hypoparathyroidism presents with the symptoms of hypocalcemia. It may present acutely, requiring immediate treatment. Serum magnesium level may be low. It is an uncommon endocrine deficiency disease characterized by low serum calcium levels, elevated serum phosphorus and absent or inappropriately low levels of parathyroid hormone (PTH) in the circulation. 25 Hydroxy vitamin D3 is normal in hypoparathyroidism but 1,25- dihydroxyvitamin D3 is low because PTH is not available.

Hypoparathyroidism is one endocrine deficiency disorder for which the missing hormone is not the standard therapy. Symptomatic hypocalcemia in acute stage is managed with continuous infusion of 10% calcium gluconate diluted in 100 ml 5% dextrose.[4] The actual value of corrected calcium level is often regarded as a threshold for acute management. The current options of chronic management include oral calcium 1.5-2.0 g/day, magnesium (if deficient), vitamin D (including its metabolites especially 1,25-dihydroxyvitamin D3 as calcitriol 0.5-1.0 μg daily) and thiazide diuretics (reduce urinary calcium excretion).[5] Treatment is lifelong.

Hypoparathyroidism itself is a rare endocrine deficiency disorder. Its association with Wilson's disease is even rarer. Certain neurological manifestations of Wilson's disease like rigidity and tremors are aggravated by hypocalcemia and are partly relieved by restoring calcium.