Lesch-Nyhan Syndrome: Symptoms, Causes And Treatment
Lesch-Nyhan syndrome is a genetic and metabolic disorder which affects children from birth and causes serious neurological disorders, cognitive alterations and various behavioral problems.
This article addresses this syndrome, its symptoms, how it is diagnosed and the main treatments available.
Lesch-Nyhan syndrome is a hereditary disease, described in 1964, that affects purine metabolism (nitrogen compounds that form, together with other nucleotides such as pyrimidines, nucleic acids such as DNA and RNA), and whose cause is a mutation of a gene located on the X chromosome, of recessive inheritance (which means that both genes must be abnormal to cause the disorder).
The genetic error that produces this syndrome generates a deficiency of the enzyme – hypoxatine-guanine-phosphoribosyl-transferase (HPRT), whose most prominent consequence at the metabolic level is a marked overproduction of uric acid levels in the body, as well as a whole series of neurological and behavioral problems.
The prevalence of Lesch-Nyhan syndrome has been estimated at around 1 in 380,000 and 1 in 235,000 newborns. This sickness It mainly affects men although heterozygous women (who have two different alleles of the gene) are also carriers (and usually asymptomatic).
The onset of the disorder occurs in childhood and, until now, two forms of the disease have been described: LNS (the most severe variant, which causes a complete absence of HPRT) and Lesch-Nyhan variants, the consequence of which is a partial deficiency of the enzyme. The LNS variant produces urolithiasis (presence of stones in the kidneys or urinary tract) and gout, associated with the overproduction of uric acid, in addition to serious neurological disorders, hematological alterations and self-harming behaviors.
In the less severe form of LNS, also known as Kelley-Seegmiller syndrome although most of the clinical manifestations of Lesch-Nyhan syndrome occur, self-harming behaviors are not present and patients have a normal life expectancy.
Symptoms
Lesch-Nyhan syndrome is characterized by three main symptoms: neurological problems, cognitive disorders and overproduction of uric acid
One of the first symptoms of this disease is the appearance of orange uric acid crystals, which usually soak the affected child’s diaper. The overproduction of this compound subsequently causes the formation of stones 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 in this disorder is the self-injurious behavior that patients present , who need to compulsively bite their fingertips and lips; a behavior very similar to the compulsions that occur in obsessive-compulsive disorder. These symptoms of self-mutilation can be exacerbated by stress.
Children with Lesch-Nyhan syndrome also present psychomotor delay , which usually becomes evident between 3 and 6 months of age: sitting is delayed, they cannot hold their head, they present hypotonia and athetoid-type movements. This disorder also causes children to be unable to stand and walk, or perform involuntary movements triggered by voluntary acts (choreoathetosis and ballismus).
It is also common for patients to suffer from dysarthria (difficulty articulating sounds), dysphagia (alterations when swallowing food) and muscular problems, such as opisthotonos. Spasticity, hyperreflexia or the Babinski sign (the dorsal extension of the big toe, accompanied by the fanning out of the rest of the toes) usually appear late.
A possible Lesch-Nyhan syndrome is usually suspected when the child presents psychomotor delay, with high levels of uric acid in the blood and urine. Since the activity of the HPRT enzyme is undetectable in the peripheral blood or in healthy cells (erythrocytes or fibroblasts), The diagnosis is usually made through molecular genetic testing
Prenatal diagnosis is possible if the genetic mutation has also been identified in the family, since inheritance is recessive and is linked to the X chromosome. In this sense, genetic counseling is important.
On the other hand, when making the differential diagnosis of this disease, the following disorders must be taken into account: cerebral palsy, dystonia, other causes of intellectual deficit, autism, Tourette syndrome, Cornelia de Lange syndrome, idiopathic intellectual deficit and serious psychiatric disorders.
Treatment
The neurological disorders and behavioral problems caused by Lesch-Nyhan syndrome generate significant motor problems in the child and his family, since the child will not be able to stand, crawl or move , nor grasping or holding heavy objects, with the consequences that this entails. This can be treated with a psychomotor expert and with physical therapy.
Since the syndrome can cause intellectual disability, this It can make it difficult for the child to be able to focus correctly, thus generating serious learning problems , as their ability to analyze and understand is compromised. In this sense, it is necessary that an occupational therapist intervenes and a speech therapy and educational approach is carried out.
Medical follow-up is also important Normally, pharmacological treatment is usually done with allopurinol, a medication used to treat hyperuricemia and its complications.
It is also essential to emphasize emotional and social needs, which must be correctly attended to. Children affected by Lesch-Nyhan syndrome need constant supervision and someone to guide them to make their daily lives more bearable. It is also important that family members are cared for and accompanied, since the impact on their daily functioning will be considerable.
Finally, with regard to schooling, It is usually difficult to include these children in a regular school The affected children have special educational needs that cannot be addressed within the framework of the measures to address diversity in regular schools, so it is common to propose that the child be schooled in a special education center or a similar center.
