Lesch-Nyhan syndrome; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency

Etiology

• deficiency in HPRT1 results in purine excess

Epidemiology

rare

Pathology

• urate crystals may form in joints, kidneys, central nervous system, & other tissues

Genetics

• X-linked recessive disease
• associated with defects in HPRT1

Clinical manifestations

• self-mutilating behaviors such as biting of lips & fingers &/or head banging
• symptoms usually occur 3-6 months of age
• urate crystals often appear as orange-colored crystal-like deposits (orange sand) in diapers
• nephrolithiasis
• hematuria
• arthritis (gout)
• dysphagia
• vomiting
• renal insufficiency
• irritability
• uncontrolled aggressive and/or compulsive actions
• hypotonia
• spasms
• athetosis
• chorea
• facial grimacing
• moderate mental retardation common

Laboratory

• increased levels of uric acid in serum & urine
• complete blood count (CBC) (monitor for megaloblastic anemia)

Complications

• megaloblastic anemia may occur

Management

• symptomatic
• allopurinol to reduce serum & urinary uric acid
• kidney stones may be treated with lithotripsy
• no standard treatment for neurological symptoms
  • some symptoms may be relieved with carbidopa/levodopa, diazepam, phenobarbital, or haloperidol
• prognosis is poor
  • no treatment for the neurological defects
  • uric acid deposition in tissues causes agonizing episodes of self-mutilation & may result in severe retardation &, ultimately, death

More general terms

• syndrome
• X-linked disease
• enzyme deficiency

Patient information

Lesch-Nyhan syndrome patient information

Database

• OMIM: https://mirror.omim.org/entry/308000
• OMIM: https://mirror.omim.org/entry/300322