Review Question - QID 214958

This patient who presents with developmental delay, choreoathetosis (writhing movements), and self-mutilation behavior most likely has Lesch-Nyhan syndrome. This disease is caused by a defect in the hypoxanthine-guanine phosphoribosyl pyrophosphate transferase enzyme that transfers phosphoribosyl groups to purines.

Lesch-Nyhan syndrome is an X-linked recessive genetic disorder that is caused by a mutation in the hypoxanthine-guanine phosphoribosyl pyrophosphate transferase (HGPRT) enzyme. This enzyme functions in the purine salvage pathway by transferring phosphoribosyl groups from 5-phosphoribosyl 1-pyrophosphate (PRPP) to purine metabolites. This process allows for the regeneration of metabolized purine subunits and a defect in HGPRT will lead to impaired conversion of hypoxanthine to inosine monophosphate and guanine to guanine monophosphate along with excess uric acid production. Patients who are affected by Lesch-Nyhan syndrome will classically present with developmental delay, choreoathetosis, self-mutilation, orange "sand" crystals in diapers, and hyperuricemia resulting in gout later in life. Treatment consists of supportive therapy and prevention of self-injurious behavior.

Incorrect Answers:
Answer 1: Methylated-CpG binding is defective in Rett syndrome, which is caused by a mutation in methyl-CpG binding protein-2. This disease will also present with hand-wringing behavior in young girls; however, self-injurious behavior would not be seen.

Answer 3: Ribosomal formation is defective in Prader-Willi syndrome, which is commonly caused by a mutation in small nuclear ribonucleoprotein polypeptide N. This disease may also present with developmental delay and consumption of strange objects in childhood; however, self-injurious behavior would not be seen.

Answer 4: Ubiquitin ligation is defective in Angelman syndrome, which is caused by a mutation in the UBE3A ubiquitin ligase subunit. This disease may also present with developmental delay as well as hand flapping; however, it also features frequent and inappropriate laughter rather than self-injurious behavior.

Answer 5: Xanthine oxidation is mediated by xanthine oxidase and may be overactive in patients who develop gout. Though this enzyme also functions in the purine salvage metabolic pathway, it is not implicated in syndromic causes of developmental delay.

Bullet Summary:
Lesch-Nyhan syndrome is caused by a mutation in the hypoxanthine-guanine phosphoribosyl pyrophosphate transferase enzyme resulting in defective phosphoribosyl transfer activity in the purine salvage pathway.