An Overview of Lesch-Nyhan Syndrome

A rare genetic disorder

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Caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT), Lesch-Nyhan syndrome is a rare genetic disorder that occurs most often in males. It leads to an overproduction of uric acid (a waste product) in the bloodstream; this can, in turn, lead to the development of gouty arthritis as well as kidney and bladder stones.

The condition also manifests as a range of neurological symptoms, including abnormal involuntary muscle movements, with most with this condition being unable to walk. Self-injury behaviors such as head banging and nail-biting are also commonly seen.

Symptoms

Signs of Lesch-Nyhan syndrome are usually first seen when a child is as young as six months old, and female carriers tend to not display symptoms. These include:

  • Orange sand: In infants with the condition, the excess production of uric acid can lead to orange deposits often called “orange sand” in the diapers.
  • Urate stones: Infants may also develop crystals in the kidneys, which can lead to blood in the urine and raises the risk of urinary tract infection.
  • Pain and swelling in the joints: In teens and adults, urate crystals can form in the joints of untreated individuals, leading to gout-like pain and swelling.
  • Cartilage deposits: Older children with the disorder often have uric deposits that collect in cartilage. When these cause bulges in the ears, the condition is called tophi.
  • Dystonia: Many of those with this condition experience dystonia—characterized by involuntary writhing in the arms and legs.
  • Chorea: Another issue that arises is chorea—involuntary, purposeless, and repetitive body movements. These can include grimacing, shoulder raising and lowering, as well as finger flexing.
  • Hypotonia: In infants, Lesch-Nyhan syndrome can lead to under-development of certain muscle groups, sometimes leading to an inability to hold the head up.
  • Developmental delay: Infants and toddlers with the condition may also experience delayed developmental milestones, such as sitting up, crawling, and walking.
  • Hypertonia: Children with this condition may develop hypertonia, defined as over-developed musculature. Often, this is paired with spasticity—increased rigidity of muscles.
  • Spasticity: Rigidity of the tendons, termed hyperreflexia, is also seen in these cases.
  • Intellectual disability: Moderate intellectual disability often occurs with this condition, though many with it do not display this symptom.
  • Dysarthia: The ability to articulate speech and pronounce words—dysarthia—is also a common hallmark.
  • Self-Mutilation: Approximately 85% of those with Lesch-Nyhan syndrome display self-mutilating behaviors, such as compulsive lip, hand, or finger biting as well as head banging. These symptoms typically arise between the ages of 2 and 3.
  • Dysphagia: Children and infants often also have dysphagia, defined as an inability to swallow effectively.
  • Behavioral abnormalities: Some children with the condition may find it difficult to control behaviors and are prone to screaming and irritability.
  • Muscle spasm: Lesch-Nyhan syndrome is often characterized by strong muscle spasms that lead to severe arching of the back. The head and heels in these cases can also bend backward.

Causes

Lesch-Nyhan syndrome is caused by a mutation of the HPRT1 gene, which hinders the production of the HGPRT enzyme. This enzyme plays the important role of recycling purines, which are constituent elements of the body’s genetic material. The build-up of uric acid in the body, then, is a result of insufficient levels of HGRPT. Neurological effects of this condition are believed to occur because of low levels of the brain chemical, dopamine.

The condition follows what’s called an X-linked inheritance pattern. This means that mutations occur in the X chromosome, one of the two that determine sex. Women, who have two X chromosomes, display Lesch-Nyhan syndrome when both have this mutation; this is why this condition is rarer among females. On the other hand, men—who have an X and a Y chromosome—will have symptoms when the X chromosome has this mutation. 

Diagnosis

Since an elevated level of uric acid in the blood is a hallmark of the condition, blood testing can identify Lesch-Nyhan syndrome. Specifically, the absence of HGPRT in tissues will confirm diagnosis. Genetic testing, in which expectant parents are tested for mutations of the HPRT1 gene, can also be conducted to determine carriers. In addition, an approach called enzyme analysis—which measures levels of enzymes—can be used prenatally.

Treatment

Since Lesch-Nyhan syndrome can express itself in many different ways, treatment approaches are focused on the management of individual symptoms. This means that care often requires collaboration between different types of specialists and caregivers. Work may involve everything from physical therapy to aid in locomotion, work with orthopedists, and behavioral therapies aimed at taking on self-mutilating behaviors. Unfortunately, there is no “silver bullet” cure for this condition. Still, there is a range of pharmaceutical and other therapies that can help, including:

  • Allopurinol: This drug helps reduce the excessive levels of uric acid endemic to the condition, though it doesn’t take on any of the neurological or physical symptoms directly. 
  • Extracorporeal shock wave lithotripsy (ESWL): This therapy takes on the kidney stones that can accompany Lesch-Nyhan syndrome. Basically, it involves the use of shock waves to target the kidneys and dissolve the problematic build-ups.
  • Benzodiazepine/diazepam: These drugs are often prescribed to help take on the spasticity associated with this syndrome and can also help with any related anxiety.
  • Baclofen: This drug also helps with spasticity and aids in taking on some of the behavioral symptoms.
  • Restraints: Physical implements like restraints of the hips, chest, and elbows may be used in children with the condition to prevent self-mutilating behaviors. In addition, mouth guards may be used to prevent bite injuries.  

Coping

Since Lesch-Nyhan syndrome is genetic, it can severely impact the quality of life not only of those with it but of loved ones as well. Certainly, management of the condition is multifaceted and will require a long-term and sustained effort, and family therapy can help manage the emotional fallout of the process.

Though the condition is rare, there are a number of public-minded resources available to help those with the syndrome and their families cope. For instance, advocacy groups and organizations such as Genetic and Rare Diseases (GARD) Information Center, the International Center for Disability on the Internet, and the International Lesch-Nyhan Disease Association do a great job of connecting communities and sharing information about the condition. 

A Word From Verywell

While there’s no overstating the challenges presented by Lesch-Nyhan syndrome, the good news is that our understanding of this condition is growing. This means that therapies are getting better and more effective and that outcomes are improving; certainly, there is cause for optimism. Though difficult, it’s important to remember that, with the right kind of help, this condition can be effectively managed and quality of life preserved. 

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  1. National Institutes of Health Genetics Home Reference. Lesch-Nyhan syndrome. Updated 2019. 

  2. National Organization for Rare Disorders. Lesch Nyhan syndrome. Updated 2020.

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