Key details
- Understanding Lesch-Nyhan syndrome: This rare, recessive condition linked to the X chromosome primarily affects boys, and is characterized by a deficiency of the HPRT enzyme, leading to severe motor dysfunction, uric acid overproduction, and compulsive self-injury.
- Role of HPRT: Used by the body to process and recycle purines: organic compounds that are a type of building block of DNA and RNA.
- Promising transplant results: A recent case study demonstrated that a cord blood transplant (from a 5/6 HLA-matched donor) successfully restored HPRT1 protein levels to normal range and prevented the onset of self-injury behavior.
- Cord blood efficacy: Umbilical cord blood is often considered the preferred stem cell source for treating inborn errors of metabolism because it supports successful engraftment and is safer than other sources when the donor and patient are not a perfect genetic match.
What is Lesch-Nyhan syndrome?
Lesch-Nyhan syndrome is a rare condition which occurs almost exclusively in boys. It is classified as an inborn error of metabolism, meaning it is congenital (present at birth), inherited, and involves a malfunction in the body’s chemical processes (metabolism). It affects a child’s brain and behavior, as well as causing overproduction of uric acid, a waste product which is normally eliminated through the kidneys.[1][2][3][4] Symptoms include:
- Urate crystals: Forming in the urine due to the build-up of uric acid, these orange-colored crystals can deposit in the diapers of babies with this condition. They are often the first symptom to appear.
- Motor issues: These begin to manifest around four months of age, with decreased muscle tone (hypotonia) resulting in a limp, “floppy” appearance and poor head control being one of the earliest symptoms. This is followed by involuntary muscle spasms (dystonia), repetitive movements (chorea) and flailing of the limbs (ballismus), as well as muscle rigidity (spasticity). Opisthotonos, a severe muscle spasm which causes the back to arch and the head and heels to bend backwards, can also occur. Babies can miss developmental milestones such as sitting, crawling or walking; those who had previously learned to sit upright typically regress and lose the ability. Most people with Lesch-Nyhan syndrome cannot walk, are unable to sit without support, and generally use a wheelchair. Speech can be slurred or poorly articulated (dysarthria); problems with swallowing (dysphagia) can also occur.
- Gout: The accumulation of uric acid in the joints eventually leads to recurring pain and swelling, similar to what happens in adults with gout. These episodes generally begin in the late teens to early adulthood, and can become progressively more frequent over time.
- Intellectual disability: Some cognitive impairment is typically present, although it is hard to gauge accurately due to the motor issues and dysarthria.
- Self injury: This compulsive behavior is a hallmark of Lesch-Nyhan syndrome, occurring in a majority of patients (about 85%), and typically begins in early childhood. It includes biting of the cheeks, lips, fingers or hands, as well as banging the head or limbs against hard objects, scratching the face, or poking at eyes.
- Behavioral issues: Patients with Lesch-Nyhan syndrome may also have episodes in which they act aggressive and attempt to injure others, or become verbally abusive.[3][4]
What causes Lesch-Nyhan syndrome?
Lesch-Nyhan syndrome is caused by a genetic mutation, and is inherited in an X-linked recessive pattern. The affected gene, HPRT1, is located on the X chromosome; this means that females are mostly carriers as they’re often protected by an unaffected X chromosome, and males who inherit the defective chromosome from their mothers are affected by the condition. Occasionally, Lesch-Nyhan syndrome can also develop in a family with no history of it. This is known as a spontaneous, or de novo, mutation.
Whether inherited or spontaneous, the mutation results in a severe shortage or complete absence of the HPRT1 protein. The body uses this protein to process and recycle purines, organic compounds which are a type of building block of DNA and RNA. Without this protein, purines are instead broken down but not recycled, resulting in abnormally high levels of uric acid in the blood. When too much uric acid is produced, the kidneys can’t keep up, and uric acid accumulates in the body.[1][2][3][4]
It is still unclear how Lesch-Nyhan syndrome affects the brain, causing the neurological and behavioral issues associated with the condition. Researchers suspect that it may either impact the levels of dopamine, an important chemical messenger required for the brain to function correctly, or reduce the function of dopamine receptors.[2][4]
Is there a cure for Lesch-Nyhan syndrome? What treatment is available?
There is no cure for Lesch-Nyhan syndrome. Treatment primarily aims to treat symptoms, and is generally handled by a team of specialists rather than a single treating physician.[2][3]
Treatment can include:
- Allopurinol, a medication normally used for gout, to reduce the amounts of uric acid present in the body and control the symptoms caused by it.
- Procedures to break down kidney or bladder stones.
- Physical splints or restraints to prevent self-injury, including hip, chest and elbow restraints as well as a mouth guard.
- Supportive equipment such as a wheelchair.[2][3]
No standard treatment is available for the neurological and behavioral symptoms of Lesch-Nyhan syndrome, although a variety of medication may help ameliorate some of them.[2][3][5][6]
Could a cord blood transplant help with Lesch-Nyhan syndrome?
If performed early enough, a cord blood transplant could potentially slow or halt the progression of Lesch-Nyhan syndrome. A recently published case study, detailing the results of a cord blood transplant for Lesch-Nyhan syndrome, provides the strongest evidence to date for this.[7]
The patient, a boy, initially presented at six months of age with hypotonia, inability to roll over, and occasional opisthotonos. MRI and EEG results raised the suspicion of Lesch-Nyhan syndrome, which was confirmed with genetic testing. Crucially, the diagnostic confirmation happened before the onset of any self-injury compulsion.
As the condition was progressing and the patient did not have a matched sibling donor, doctors made the decision to proceed with a cord blood transplant from a partially matched (5/6 HLA) donor, performed at 14 months old.
The outcome of the transplant was positive:
- Treatment safety: 28 days post-transplant, the patient had mild graft-versus-host disease (GvHD), a condition in which white blood cells remaining in the donated graft attack the cells of the host’s body. This was resolved with corticosteroids, a medication which reduces inflammation and suppresses the immune system. Beyond this, there were no complications, and the boy remained free of GvHD by the time the case report was submitted for publication.
- Successful engraftment: Complete donor chimerism, meaning over 95% of the patient’s new blood cells were of donor origin, was achieved on day 32 post-transplant.
- HPRT1 protein levels: Prior to the transplant, the patient’s HPRT1 protein levels were low (40.9 pg/ml) compared to those of his father and mother (98.8 pg/ml and 78.9 pg/ml respectively). Post-transplant, levels rose to 91.1 pg/ml by day 32 and remained normal (97.0 pg/ml) at day 126.
- Neurological improvement: The patient’s dystonia and spasticity decreased, opisthotonos became more infrequent, and he had improved facial expressions, increased social interaction and developmental progress. At 36 months of age, he still showed no sign of any self-injury behavior.[7]
This case shows a promising result, but research is still in the very early stages. Including this case, only three hematopoietic stem cell transplants (HSCT) have been performed in children with Lesch-Nyhan syndrome before the onset of the self-injury compulsion:
| Endres et al. (1991) | Kállay et al. (2012) | Weng et al. (2025) | |
| Patient age | 16 months | 24 months | 14 months |
| Stem cell source | Bone marrow | Cord blood (6/6 match) | Cord blood (5/6 match) |
| Outcome | Death (day +10) | Survival, full chimerism | Survival, full chimerism |
| Long-term outcome | N/A | No self-injury at 5yr follow-up. Persistent motor delay. | No self-injury at 36mo. Improved dystonia/social. |
Thus, no formal protocol for this treatment has been established yet. Instead, until more evidence is available, the decision on whether a transplant is appropriate should be made individually for each case, by a coordinated multidisciplinary team including ethical oversight, with transparent family counseling so that informed parental consent is possible.[7]
What is known for certain is:
- HSCT has been successfully used to treat other conditions in the inborn error of metabolism category, and is the standard of care for some of them, such as Hurler syndrome [8] and Krabbe disease.[9]
- Cord blood is generally the preferred stem cell source for such transplants, as it increases the likelihood of full donor chimerism and is safer to use when the donor and the patient aren’t a perfect genetic match.[7][8][10]
In the case of Krabbe disease, specifically, early transplantation is of paramount importance; the sooner a transplant happens, the better the functional results for the child, with differences being noticeable even between children transplanted before 30 days of age and those transplanted after.[11] In the United States, several states have implemented newborn screening for Krabbe disease because of this. Here, too, cord blood presents itself as a superior stem cell source, as families may have previously banked the cord blood from an unaffected sibling and, if not, a matched cord blood unit may be available in a public bank.
Should a newborn screening targeted at Lesch-Nyhan syndrome be implemented, it would mean the condition could be identified before symptoms develop. The authors of this case study speculate that early transplant could prevent irreversible neuronal loss and preserve neurological potential.[7]
The importance of family banking
Storing your baby’s cord blood privately gives them access to their own perfectly matched stem cells, and a 75% chance they could be a match for a sibling who may need a transplant; comprising a 25% chance of a perfect match, and 50% chance of a partial match.
As the regenerative medicine field continues to advance, researchers are also investigating the potential of autologous stem cell treatments, using patients’ own stem cells. These would involve gene editing techniques such as CRISPR, and have already become available for some inherited conditions, such as sickle cell disease and beta thalassemia; for other conditions, including Lesch-Nyhan[12] and Krabbe disease, they are in pre-clinical or clinical trial stage. For any of these conditions, it is also possible that the most effective treatment would be a combination of cord blood transplant and gene therapy; this is currently being investigated for Krabbe disease.[13]
Should you choose to bank your baby’s cord blood, it is possible that the stem cells it contains could be used for autologous treatments, rather than more invasively collected bone marrow or peripheral blood stem cells. Should your baby prove to be a donor match for one of their siblings or another family member who is in need of a transplant, the cord blood could potentially also be used in that case.
To learn more about banking your baby’s cord blood, as well as about other sources of stem cells that can only be collected immediately after birth, fill in the form below to request your free info kit.
References
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