Lesch-Nyhan syndrome: symptoms, causes and treatment

This genetic disorder is associated with cognitive and psychomotor disturbances.

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

This article discusses this syndrome, its symptoms, how it is diagnosed and the main treatments available.

What is Lesch-Nyhan syndrome?

Lesch-Nyhan syndrome is a hereditary disease, described in 1964, that affects purine metabolism. (nitrogenous compounds that form, along 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, recessive inheritance (which means that both genes must be abnormal to cause the disorder).

The genetic error that produces this syndrome generates a deficit of the enzyme - hypoxatin - guanine - phosphoribosyl - transferase (HPRT), whose most prominent consequence at the metabolic level is a marked overproduction of uric acid levels in the organism, as well as a 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 disease mainly affects males.The onset of the disorder occurs in childhood and, so far, two forms of the disease have been described: LNS (the most severe variant), which results in the complete absence of HPRT, and Lesch variants of Lesch (the most severe variant), which results in the complete absence of HPRT.

The onset of the disorder occurs in childhood and, so far, two forms of the disease have been described: LNS (the most severe variant), which causes a complete absence of HPRT) and Lesch-Nyhan variants, which result in a partial deficit of the enzyme. The LNS variant causes urolithiasis (presence of kidney or urinary tract stones) and gout, associated with the overproduction of uric acid, as well as severe neurological disorders, hematological disorders and self-injurious behavior.

At In the less severe form of LNS, also known as Kelley-Seegmiller syndromesyndrome, although most of the clinical manifestations of Lesch-Nyhan syndrome occur, self-injurious behaviors are absent 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-colored uric acid crystals, which usually soak the diaper of the affected child. The overproduction of this compound subsequently causes the formation of stones in the kidneys, urethra or bladder, which are deposited in the joints and eventually lead to Arthritis and other conditions (gout, joint pain, etc.).

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

Children with Lesch-Nyhan syndrome also present psychomotor retardation, which is usually evident between 3 and 6 months of age.This is usually evident between 3 and 6 months of age: sitting is delayed, they cannot hold up their head, they have hypotonia and athetoid-like movements. This disorder also causes children to be unable to stand and walk, and to perform involuntary movements triggered by voluntary acts (choreoathetosis and ballism).

Patients also frequently suffer from dysarthria (difficulty articulating sounds), dysphagia (impaired swallowing of food) and muscular problems such as opisthotonos. Spasticity, hyperreflexia or Babinski's sign (dorsal extension of the big toe, accompanied by the fan-shaped opening of the other toes) usually appear late.

Diagnosis

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

Prenatal diagnosis is possible if the genetic mutation has also been identified in the family, since inheritance is recessive and X-linked. In this sense, genetic counseling is important.

Moreover, 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 syndrome, Cornelia de Lange syndrome, idiopathic intellectual deficit and severe psychiatric disorders.

Treatment

The neurological disorders and behavioral problems caused by Lesch-Nyhan syndrome generate, in the child and his family, important problems at the motor level, since the child will not be able to stand, crawl or move around, nor will he/she be able to grasp or hold weighted objects.The child will not be able to hold or grasp heavy objects, with the consequences that this entails. This can be treated with an expert in psychomotor skills and physiotherapy.

As the syndrome can lead to intellectual disability, this can make it difficult for the child to may make it difficult for the child to focus his or her attention correctly, leading to serious learning problems, as the child's ability to pay attention is compromised.The child's capacity for analysis and comprehension may be compromised. In this sense, it is necessary that an occupational therapist intervenes and a logopedic and educational approach is made.

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

It is also essential to emphasize emotional and social needs, which must be properly addressed. Children affected by Lesch-Nyhan syndrome need constant supervision and guidance to make their daily lives more manageable. It is also important that family members are cared for and accompanied, as the impact on their daily functioning will be considerable.

Finally, as far as schooling is concerned, it is often difficult to include these children in school, it is often difficult to include these children in a regular school.. The children concerned have special educational needs that cannot be addressed within the framework of the diversity measures in regular schools, so it is common to propose that the child be placed in a special education center or a similar center.