What is Lesch-Nyhan Syndrome?
This disease, also known as self-destructive syndrome, is a special recessive genetic disease with X chromosome. The mutant gene is located on chromosomes Xq26 ~ q27.2. It has been clarified that the etiology is due to the lack of activity of hypoxanthine-guanine phosphoribosyl transferase (HGPRT), an enzyme in the purine nucleotide metabolism in the body, resulting in the purine nucleotide update Metabolic over-synthesis activates hypoxanthine and guanine to the corresponding nucleotides, and leads to a large accumulation of uric acid, the final product of purine metabolism in children's body fluids, resulting in various brain and kidney damage. [1]
Lesch-Nyhan syndrome
- This disease, also known as self-destructive syndrome, is a special recessive genetic disease with X chromosome. The mutant gene is located on chromosomes Xq26 ~ q27.2. It has been clarified that the etiology is due to the lack of activity of hypoxanthine-guanine phosphoribosyl transferase (HGPRT), an enzyme in the purine nucleotide metabolism in the body, resulting in the purine nucleotide update Metabolic over-synthesis activates hypoxanthine and guanine to the corresponding nucleotides, and leads to a large accumulation of uric acid, the final product of purine metabolism in children's body fluids, resulting in various brain and kidney damage. [1]
Lesch-Nyhan syndrome pathology
- The kidneys atrophy, and a large amount of urate crystals are seen in the renal tubules. There are multiple demyelinating changes in the white matter of the brain and cerebellum. Cerebral cortex has brown pigmentation, cerebellar cortex atrophy, granulosa cells decrease, Purkinje cell granules degeneration, and often accompanied by multiple micro-infarcts. In brain tissue fixed with alcohol, birefringent uric acid crystals are sometimes seen.
Essentials of Lesch-Nyhan syndrome diagnosis
Overview of Lesch-Nyhan syndrome
- Based on typical neurological symptoms and hyperuricemia, general diagnosis is not difficult. But in atypical cases or those with low uric acid, leukocytes or skin fibroblasts need to be cultured and tested for HGPRT activity. Molecular probes can also be used to directly detect point mutations on the long arms of the X chromosome to confirm the diagnosis.
Clinical manifestations of Lesch-Nyhan syndrome
- All occur in boys, and women can be asymptomatic as carriers of genes. The child was completely normal at birth, and most of them found developmental stagnation, repeated vomiting, and low general muscle tone from 3 to 4 months. At 7-8 months, subtle movements of hands and feet or dance-like involuntary movements gradually appear. At this time, the athletic ability that has been learned begins to degenerate or lose again, the muscle tone also changes from low to high, and there is hypertenous reflex, ankle clonus, or limb contracture. Intellectual development has gradually stopped, often showing restlessness, crying, ambiguity, etc., and about half of children have seizures. It can also be accompanied by various types of congenital malformations. The self-injury behavior occurred from about 2 to 3 years old. First, biting the lip and tongue, then it can develop into unrestrained biting fingers, biting people, and destroying clothing. In addition, gouty joint pain is one of the common symptoms of this disease, and older children can develop gout nodules.
Lesch-Nyhan syndrome laboratory test
- The uric acid content in various body fluids increased significantly, and the ratio of uric acid / creatinine (UA / Cr) also increased. Orange-red crystals of uric acid or urinary stones are often found in the urine. Eosinophils often increase in the blood, and often have large cell anemia. CT or MRI images show cerebral atrophy and enlarged ventricles. [1]
Overview of Lesch-Nyhan syndrome treatment
- There is currently no effective treatment for neurological symptoms. Anti-gout treatment with allopurinol (200 to 400 mg daily), sodium glutamate (3 to 5 g daily), or probenecid (carbesulfenamide) can only reduce joint pain. Gene therapy using gene recombination technology is a promising prospect and is currently being studied. [1]