Radiological Diagnosis

lesch-nyhan syndrome

Radiographs of both ankles and feet revealed calcific intraosseous tophi in the lateral malleoli, base of the first metatarsal on the right and base of the middle phalanx of the third toe on the left associated with soft tissue swelling. These was associated overproduction of uric acid with nephrocalcinosis seen on ultrasound.

It is an X-linked recessive disorder caused by deficiency of the enzyme hypoxanthine/guanine phosphoribosyl transferase which catalyses the conversion of hypoxanthine to inosine monophosphate and guanine to guanine monophosphate in the presence of phosphoribosyl pyrophosphate [1]. This syndrome is characterised by neurological dysfunction, both cognitive and behavioral disturbances with uric acid overproduction [1]. The neurological findings closely resemble athetoid cerebral palsy. The common presenting features are hypotonia and developmental delay, which are evident by three to six months of age. Patients are cognitively impaired and have behavioral disturbances that emerge between two to three years of age. Persistent self-injurious behaviour (biting of the fingers, hands, lips, cheek and banging of the head or limbs) is a hallmark of the syndrome[2]. Both CT and MRI may show non-specific changes of atrophy of the basal ganglia or cerebrum. Electroencephalogram may show non-specific changes of slowing or disorganization[3].

The serum uric acid concentration is usually, but not always, elevated since the excess purines are rapidly excreted in the urine. Overproduction of uric acid may lead to deposition of uric acid crystals or calculi in the kidneys, ureters or bladder. Crystals appear as an orange sandy material; calculi may be multiple tiny stones (gravel) or discrete large stones that are difficult to pass. The stones may cause hematuria and increase the risk for urinary tract infections. Stones may be the presenting feature of the disease, but are often not recognized for months or years. In this case there was deposition of uric acid crystals in the renal tubules [Figure - 3] resulting in medullary nephrocalcinosis[4].

Gout is uncommon in children with Lesch-Nyhan syndrome and typically develops long after features are present. The radiological changes are due to the deposition of monosodium urate in the soft tissues and bones. In chronic tophaceous gout, intra osseous tophi may form [5] and these are usually recognized as small well marginated subchondral cystic rarefactions with patchy calcification. The tophi can enlarge and destroy bone from within finally breaking out to produce erosions which tend to be periarticular and have characteristic overhanging margins as was seen in this case [Figure - 1].

The overproduction of uric acid is controlled by allopurinol to reduce the risk of nephrolithiasis and gouty arthritis. No medication has been found to be consistently effective in controlling the extrapyramidal motor features of the disease. Spasticity, when it occurs can be managed with baclofen or benzodiazepines[6]. Currently there is no uniformly effective intervention for managing the behavioral disturbances of the disease.

Genetic counselling is important in Lesch-Nyhan syndrome as it is inherited in an X-linked recessive manner and is almost exclusively found in males. The father of an affected male will not have the disease nor be a carrier of the mutant allele. The risk to siblings of a proband depends upon the carrier status of the mother. Carrier mothers have a 50% chance of mutation in each pregnancy. Sons who inherit the mutation will be affected, daughters who inherit the mutation become carriers. Thus with each pregnancy, a carrier woman has a 25% chance of having an affected male, a 25% chance of having a carrier female and thus a 50% chance of having a normal male or female[7].