Lesch-Nyhan syndrome: symptoms, causes and treatment

Lesch-Nyhan syndrome is a genetic and metabolic disorder It 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.

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What is Lesch-Nyhan syndrome?

Lesch-Nyhan syndrome is a hereditary disease, described in 1964, that affects the metabolism of purines (nitrogenous 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 (meaning 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 metabolically prominent is a marked overproduction of uric acid levels in the body, as well as a whole series of neurological and behavioral

The prevalence of Lesch-Nyhan syndrome has been estimated at around 1 in 380,000 and 1 in 235,000 newborns. This sickness mainly affects men, although heterozygous females (carrying two different gene alleles) are also carriers (and usually asymptomatic).

The onset of the disorder occurs in childhood and, up to now, two forms of the disease have been described: the LNS (the variant more severe), which causes a total absence of HPRT) and Lesch-Nyhan variants, the consequence of which is a partial deficit 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 severe neurological disorders, hematological abnormalities and behaviors self harm

In 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.

Symptoms

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

One of the first symptoms of this disease is the appearance of uric acid crystals, orange in color, 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, that 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 compulsively need to 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 retardation, which usually becomes evident between 3 and 6 months of age: sitting is delayed, they cannot support their heads, they present hypotonia and athetoid-type movements. This disorder also causes children to be unable to stand up and walk, or make 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 Babinski's sign (dorsal extension of the big toe, accompanied by fanning out of the rest of the toes) usually appear late.

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Diagnosis

A possible Lesch-Nyhan syndrome is usually suspected when the child presents psychomotor retardation, with high levels of uric acid in the blood and urine. As HPRT enzyme activity is undetectable in peripheral blood or healthy cells (erythrocytes or fibroblasts), 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 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 should be taken into account: cerebral palsy, dystonia, other causes of intellectual deficit, autism, Tourette syndrome, Cornelia de Lange syndrome, idiopathic intellectual deficit and disorders serious psychiatric

Treatment

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

Since the syndrome can lead to intellectual disability, this It can make it difficult for the child to be able to focus her attention correctly, thus generating serious learning problems., as their ability to analyze and understand is compromised. In this sense, it is necessary for an occupational therapist to intervene and a logopedic and educational approach is made.

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

It is also essential to put the accent on affective and social needs, which must be properly attended. Children affected by Lesch-Nyhan syndrome need constant supervision and someone to guide them to make their day to day 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 be able to include these children in an ordinary school. The children affected have special educational needs that cannot be addressed within the framework of attention to diversity measures. ordinary centers, so it is common to propose to enroll the child in a special education center or in a center similar.