Lesch-Nyhan syndrome: symptoms, causes and treatment

Lesch-Nyhan syndrome is a genetic and metabolic disorder which affects children from birth and causes severe neurological disorders, cognitive impairment and various behavioral problems.

This article discusses this syndrome, its symptoms, diagnosis and the main treatments available.

    What is Lesch-Nyhan syndrome?

    Lesch-Nyhan syndrome is an inherited disease, described in 1964, that affects the metabolism of purines (Nitrogenous compounds which, along with other nucleotides such as pyrimidines, form nucleic acids such as DNA and RNA), and the cause is a mutation of a gene located on the X chromosome, of inheritance recessive. Means that both genes must be abnormal to cause the disorder).

    The genetic error that produces this syndrome generates a deficiency of the enzyme – hypoxatin-guanine – phosphoribosyl – transferase (HPRT), the most important consequence at the metabolic level is a marked overproduction of uric acid levels in the body, as well. a whole host of neurological and behavioral problems.

    The prevalence of Lesch-Nyhan syndrome has been estimated to be approximately 1 in 380,000 and 1 in 235,000 newborns. it mainly affects men, Although heterozygous women (who have two different genetic alleles) are also carriers (and usually asymptomatic).

    The onset of the disorder occurs in childhood and, to date, two forms of the disease have been described: LNS (the most severe variant), which causes a complete absence of HPRT) and the Lesch-Nyhan variants. The consequence is an enzyme deficiency. The LNS variant produces urolithiasis (presence of stones in the kidneys or urinary tract) and gout, associated with overproduction of uric acid, as well as severe neurological disorders, hematological alterations and self-injurious behaviors. .

    Fr the less severe form of LNS, also known as Kelley-Seegmiller syndromeAlthough most of the clinical manifestations of Lesch-Nyhan syndrome occur, self-injurious behaviors are not present and patients have a normal life expectancy.


    Lesch-Nyhan syndrome is characterized by three main symptoms: neurological problems, cognitive impairment and overproduction of uric acid.

    One of the first symptoms of this disease is the appearance of orange uric acid crystals, which usually permeate the diaper of the affected child. Overproduction of this compound subsequently causes stones to form in the kidneys, urethra or bladder, which are deposited in the joints and, over time, cause arthritis and other conditions (gout, joint pain, etc.).).

    Another of the most common symptoms of this disorder is self-injurious behavior of patients, Who need to compulsively bite their fingertips and lips; behavior very similar to the compulsions that occur in obsessive-compulsive disorder. These symptoms of self-harm can be exacerbated by stress.

    Children with Lesch-Nyhan syndrome also have psychomotor retardation, Which is usually evident between 3 and 6 months: Sedation is delayed, cannot support the head, has hypotonia and athetoid movements. This disorder also prevents children from getting up and walking, or from making involuntary movements triggered by voluntary acts (choreoathetosis and ballismus).

    It is also common for patients to suffer from dysarthria (difficulty in articulating sounds), dysphagia (trouble swallowing food), and muscle problems, such as opisthotonus. Spasticity, hyperreflexia, or Babinski’s sign (dorsal extension of the big toe, accompanied by the fan opening of the rest of the toes) usually appears late.


      A possible Lesch-Nyhan syndrome is often suspected when the child has psychomotor retardation, with high levels of uric acid in the blood and urine. As the activity of the HPRT enzyme is undetectable in peripheral blood or in healthy cells (erythrocytes or fibroblasts), the diagnosis is usually made by molecular type genetic tests.

      Prenatal diagnosis is possible if the genetic mutation has also been identified in the family, since heredity is recessive in type and is linked to the X chromosome. In this regard, genetic counseling is important.

      On the other hand, when making the differential diagnosis of this disease, the following disorders should be taken into account: cerebral palsy, dystonia, other causes of intellectual deficit, autism, Tourette’s syndrome, Cornelia de Lange, idiopathic intellectual deficit and severe psychiatric disorders.


      Neurological disorders and behavioral problems caused by Lesch-Nyhan syndrome lead to significant motor problems in the child and his family, such as the child cannot stand, crawl or move., As well as not to grab or hold heavy objects, with the consequences that this entails. This can be treated with an expert in psychomotor skills and physiotherapy.

      How the syndrome can cause intellectual disability, it can be difficult for the child to be able to focus his attention properly, causing serious learning problems., Seeing his capacity for analysis and understanding compromised. In this sense, an occupational therapist must intervene and a speech therapy and educational approach must be adopted.

      Medical follow-up is also important. Pharmacologic treatment is usually done with allopurinol, a drug used to treat hyperuricemia and its complications.

      It is also essential to focus on emotional and social needs, which must be properly met. Children with Lesch-Nyhan syndrome need constant supervision and someone to guide them to make their daily life more bearable. It is also important to take care and support loved ones, because the impact on their daily functioning is considerable.

      Finally, with regard to schooling, it is often difficult to include these children in a regular school. The children concerned have special educational needs which cannot be met under the diversity measures in mainstream schools, so it is common to offer to send the child to a special education center or to a special education center. a similar school.

      Bibliographical references:

      • Campolo González, A., Vargas Díaz, A., Fontboté Riesco, D., and Hernández Chávez, M. (2018). Lesch-Nyhan syndrome and oral self-mutilation. Report a case. Chilean Journal of Pediatrics, 89 (1), 86-91.
      • Jiménez, RT, Antón, FM, Hernández, TR, Martínez, JA, Soto, AB, and Puig, JG (1998). Biochemical, enzymatic and genetic study of hypoxanthine guanine phosphorribosyltransferase (HPRT) deficiency. Spanish Annals of Pediatrics, 48, 355-362.
      • Torres, RJ and Puig, JG (2007). Hypoxanthine-guanine phosphorybosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet Journal of Rare Diseases, 2 (1), 48.

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