Lesch Nyhan Syndrome Flashcards
What is the genetic cause and inheritance pattern of a condition in a child presenting with aggressive finger biting and symptoms of gout?
Lesch-Nyhan Syndrome
Lesch-Nyhan Syndrome is caused by an X-linked recessive mutation in the HGPRT gene, leading to hypoxanthine-guanine phosphoribosyltransferase deficiency.
What enzyme deficiency leads to the symptoms of Lesch-Nyhan Syndrome, and what metabolic pathway is affected?
The deficiency of HGPRT affects purine metabolism.
Less production of GMP and IMP.
Increased PRPP concentrations.
Overproduction of uric acid and its associated symptoms.
At what age do symptoms of Lesch-Nyhan Syndrome typically begin to appear, and what are the initial signs?
Symptoms typically begin at around six months of age and include hypotonia and developmental delay in infancy. A common failed milestone is the inability to sit up-right on their own at this age.
Patients may fail to walk unassisted by 12 years old.
By three years old the patients become dystonic, have spastic movements (chorea), and will exhibit severe and dangerous self-mutilation.
What are the key neurological and behavioral features seen in children with Lesch-Nyhan Syndrome?
The defective purine metabolism leads to neurotoxicity.
Neurological and behavioral features include intellectual disability, choreoathetosis, spasticity, and compulsive self-injury such as biting and head banging.
How does uric acid deposition manifest in Lesch-Nyhan Syndrome?
Uric acid deposition leads to gouty arthritis, tophi, and nephrolithiasis, contributing to significant morbidity.
Red and orange crystals in the patient’s urine.
Labs will show increased uric acid and other renal issues like increased creatinine.
What is the significance of orange sand-like crystals in diapers for Lesch-Nyhan Syndrome?
Orange sand-like crystals in diapers represent uric acid crystals, an early sign of hyperuricemia in affected infants.
What hematological issue is observed with Lesch-Nyhan Syndrome?
Macrocytic anemia (low hemoglobin values and increased MCV)
How is Lesch-Nyhan Syndrome diagnosed?
The diagnosis is based on clinical presentation and confirmed with genetic testing for mutations in the HGPRT gene.
What is the treatment approach for Lesch-Nyhan Syndrome, and what does it target?
Treatment includes allopurinol to manage hyperuricemia and associated symptoms. Symptomatic management of neurological and behavioral issues is also essential.
Febuxostat can also be considered as part of the treatment.
What are the complications associated with Lesch-Nyhan Syndrome that are critical to recognize?
Complications include severe gout, renal damage from nephrolithiasis, and significant disability from neurological and behavioral abnormalities. Dopamine pathway and frontal lobe neuron dysfunction also contribute to disease pathology.
