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Prevention of renal injury
The single most important health issue is the control of uric acid. Uric
acid accumulates in the blood (hyperuricemia), precipitates into the urine
(as seen as yellow crystals in the diapers), and gradually leads to fatal
injury to the kidneys. The use of the drug allopurinol which decreases
serum uric acid production has significantly altered the natural history
of LND.
The Matheny School in New Jersey has many years experience with a number of boys with LND. In The Matheny Bulletin, Vol. III, No.2, the following recommendations are offered as a "kidney protocol":
Daily: Encourage about 40 ounces of fluids per day. Because of vomiting, frequent small amounts work best.
3/week: Obtain urinalysis with specific gravity and pH assessment. If the specific gravity is greater than 1.020 or the pH is less than 6.5 or greater than 7.5 over several readings, increase fluid intake and correct acid/base status.
4/year: Monitor BUN, Serum Creatinine, Electrolytes.
Yearly: Renal ultrasound.
Yearly: Creatinine clearance; citrate, uric acid and calcium/creatinine
ratios.
Other suggestions from Matheny Bulletin include:
"….Allopurinol therapy can substantially inhibit the development
of uric acid stones, but…., xanthine stones may form if uric acid
levels are too low…"
"….When encouraging fluids, excessive milk should not be offered
for one boy developed a calcium stone when milk was his primary fluid…"
"….Kidney stones may be more prevalent in the summer or early
fall when dehydration is more likely. An air-conditioned environment is
helpful and extra fluids should be offered when temperatures are high…."
"….Alkalinizing the urine with polycitra or bicarbonate keeps
the urine neutral and minimizes stone formation…."
"….Virtually all patients with LND after the age of three have
tiny stones deposits in the kidneys at all times, despiteu appropriate
allopurinal therapy. Stones rarely become symptomatic unless fluid status
or urine pH are consistently abnormal…"
Medication to decrease
the neurological symptoms
As of now, there is no known medication that significantly alters the neurological (physical or behavioral) impact of LND. There have been anecdotal reports that Mellaril and Haldol are helpful for some individuals. Some parents have reported benefit from Risperidol. Other unpublished case reports suggest that anticonvulsive medications such as Dilantin and Tegretol are helpful. There are some recent published clinical reports that the anti-convulsant medication Gabapentine may be useful. Parent surveys (Anderson and Ernst, 1991) indicate that the most commonly used medication for the control of behavioral symptoms are the benzodiazepines. These anti-anxiety agents (Valium) are capable of taking the edge off a stressful period and help to calm the patient. Bed time medications such as Benadryl and chloral hydrate can be used to give patients and caretakers a better night sleep. Allopurinol, while successfully treating the buildup of uric acid has no impact on the neurological symptoms of the disease.
The field struggles to understand why positive results from various SIB medications do not stand up to the test of time. There have been at least two (2) well-designed studies which have reported positive effects that were substantial in nature. Individual families report positive results from various medications, also. However, upon wider use, the results do not hold up. There are two possible explanations for this phenomenon. First, the patients may be highly susceptible to the placebo effect. When new medications are given to these patients, care must be taken to minimize expectations. Second, there may be a biochemical rebound effect. Medications may indeed be initially effective, but the brain acts in a way to compensate for the change and the positive effect is gradually lost.
Anti-depressant medication
All patients should be closely monitored for depression. Depression has
been observed in boys as young as 8 and seems to be rule among the teenagers.
Psychotherapy and anti-depressant medication should be considered.
Bone marrow transplantation
There are no reports of successful bone marrow transplantation. Failures
were reported in one published report (Endres, 1991) and in three other
instances of which we are aware (personal communication).
Physical therapy
Physical therapy, even when begun at a very early age, does not lead to
improvement in the underlying neurological impairment.
Vomiting is common
Patients with LND vomit very easily. Vomiting can be a Lesch-Nyhan "behavior",
the result of esophageal dysmobility or a combination of the two. Swallowing
food and liquids is not easy for the patient, even when fully cooperating.
Because of esophageal dysmobility vomiting is easily accomplished, either
by accident or "on purpose".
Teeth Extraction
Teeth extraction is a common way to manage self-injurious biting of the
fingers, lips and cheeks. The parent survey by Anderson and Ernst (1994)
found that 60% of the patients had teeth extracted in order to prevent
self-injury. Parents overwhelmingly endorsed teeth extraction as a way
of managing self-biting. The only remorse was that they did not do it
quickly enough to prevent tissue loss, particularly to the lips. All of
the patients expressed relief at having their teeth removed. If the decision
to remove teeth is made, it is best to remove all the teeth, not just
the ones currently involved in biting. It is our experience that the patients
quickly discover ways to bite themselves using the remaining teeth. Biting
is less a problem in the older boys and it may be possible to save the
secondary molars.
Teeth extraction is a difficult decision. The most difficult factor in making the decision is that not all patients become finger and lip bitters. Some patients with LND have relatively mild forms of self-injury. In still others, self-injury is completely absent. One does not want to remove the teeth unnecessarily. But, given that the patient is showing signs of finger and lip biting, there are several arguments in favor of the decision:
The physical appearance of the child is largely unchanged. Others tend not to notice that the teeth are missing. The sunken-in appearance of the elderly who have lost their teeth is a result of loss of gums, not the loss of teeth. Whatever the physical affect of teeth extraction might be, it needs to be contrasted to the physical appearance of a child who has bitten away portions of his lips.
Problems associated with meal times and chewing food are largely unaffected. Food must be cut into small pieces and soft food must be prepared in any case. Gums become quite hard and capable of managing french fries and Big Macs.
Diction is unaffected. Clarity of speech is terrible at best, and teeth extraction is unlikely to make it any worse.
Removing the worry of self-biting makes everyone more relaxed.
Dental Guards
An alternative to teeth extraction is protective dental appliances designed
by dentists. Despite heroic attempts by dentists most (but not all) efforts
end in failure. Twenty percent of the parents who tried mouth guards report
that they found them useful saying that they "help a lot". The
other 80% found that they were not useful or became a further source of
damage.
Toilet Training
Like all behavioral issues with LND, the goal should be to keep the process
stress-free. Keeping the patient dry, free of rash and other discomfort
is the main consideration. Most boys are physically and cognitively capable
of toilet training but very few use a toilet in a normal fashion. Bathrooms
are dangerous places for a person with LND. Sharp corners and hard object
are everywhere. Using a diaper is the most common toileting method. A
hand held urinal or bed pan might prove useful.
Adaptive Equipment
Adaptive equipment is one of the most important issue in the care of LND
patients. The patients need to be up and about and participating in the
daily routine. Virtually all patients use wheelchairs and almost all require
some form of physical restraint to prevent self-injury. The wheelchair
should be custom made with inserts molded to the shape of the body. A
seat belt is used across the lap and across the chest . A three sided
head rest is used to support the head. The feet are often placed in padded
foot boxes or Velcro or buckle straps used to hold the feet tight to the
wheelchair. Many chairs have a padded saddle horn to prevent the legs
from scissoring and the torso from slipping our of the chair. Padded elbow
splints which prevent finger biting and lip gouging round out the typical
LND appearance.
A clever and creative mechanic is a Lesch-Nyhans boy's best friend. Communication boards, computer devices, electronic games, wheelchair mobility, radio and TV control, etc, provide the kinds of freedom and interpersonal interaction critical to the happiness of the patient. But each of these items are sources of potential self-injury. The creative construction of individualized devices which allow access while preventing self-injury is a constant challenge.
The following is a quote from Dr William Nyhan on the topic of adaptive equipment. Dr Nyhan has often traveled abroad to meet and study patients with LND. "…in Great Britain…..all of the affected children attend one place in Harrow. When a new patient arrives the first thing that happens is that he gets "seated". Getting seated in the English sense means that they make a cast of the patient and then they make a plastic chair in which he can be positioned as well as possible… I have also had the opportunity to see patients with LND in Japan. Since you generally do not find chairs or beds there, just a table on which you can eat, the institutions are similarly equipped. As a consequence, patients who are non-ambulatory find themselves in a place with nice soft carpets on the floor, and everyone else is also on the floor, and they get along quite well." (Proceedings of the National Conference on Lesch-Nyhan Syndrome held May 10-11, 1994, Morristown, New Jersey)