PERIPHERAL NEUROPATHY AS THE PRESENTING FEATURE OF TYROSINEMIA TYPE-IAND EFFECTIVELY TREATED WITH AN INHIBITOR OF 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE

A 21 month old girl presented with a short history of frequent falls a nd a right sided foot drop. She went on to suffer recurrent episodes o f distal weakness in her arms and legs with hyporeflexia. Electrophysi ological studies were consistent with inflammatory demyelinating polyr adiculoneuropathy (IDP) and treatment with corticosteroids appeared to lead to an improvement. However, the development of hypertension, evi dence of tubulopathy, and hepatomegaly led to reevaluation. A diagnosi s of type I tyrosinaemia was made, based on increased urinary excretio n of succinylacetone and decreased activity of fumarylacetoacetase in her cultured skin fibroblasts. A low tyrosine diet did not prevent lif e-threatening exacerbations of neuropathy but intravenous haemarginate appeared to aid her recovery from one exacerbation. An immediate impr ovement in strength was seen after starting treatment with 2-(2-nitro- 4-trifluoro-methyl-benzoyl) 1, 3-cyclohexanedione (NTBC), an inhibitor of 4-hydroxy-phenylpyruvate dioxygenase. A liver transplant was perfo rmed but the patient died of immediate postoperative complications. Ty rosinaemia needs to be considered in a child with recurrent peripheral neuropathy because (i) the signs of liver disease and renal tubular d ysfunction may be subtle; (ii) acute exacerbations may be life threate ning; (iii) specific forms of treatment are available.