Smith Lemli Opitz Syndrome: Treatment, Cost and Side Effects

Smith Lemli Opitz Syndrome is an genetic inborn disorder where in there is a disorder in the cholesterol synthesis. It is caused due to the mutation in an enzyme of the body named as the enzyme 7-Dehydrocholesterol reductase, or DHCR7. Due to these mutations various body parts are affected. In minor cases the problems can be related to learning abilities and behavioural patterns. But in severe cases facial fetaures can be distinctive, the head size may be small, and the child may face communication and social interaction problems. In some cases the heart, the lungs and genitalia may be malformed. So far, no treatment has proved to have a long-term effect on patients with Smith Lemli Opitz Syndrome. However, since primarily it is a sterols disorder, a patient's diet can be supplemented with more and more of dietary cholesterol. This cholesterol can be in the mode of purified cholesterol or foods such as egg yolks and cream. This therapy has shown to improve the symptoms in the patients. Early diagnosis and treatment help with speech and physical disabilities. Some common symptoms like vomiting, gastroesophageal reflux, and constipation can be treated with general medication. Those who have muscle spasms and mobility disabilities have to be treated either by surgery or orthotics. The Smith Lemli Opitz Syndrome can cause extreme sun sensitivity, so patients are expected to always wear sunblock, sunglasses, and appropriate clothing when they step out in the sun. Simvastatin therapy has also been proposed. The main aim of this therapy is to inhibit the HMG-CoA reductase which will diminish the build-up of toxic metabolites in the body. But in the cases of malformation, surgery is the only way out. Antioxidant supplementation is another way of treating this disease but this is still under research. The antioxidants look to stop the peroxidation of 7DHC and its derivatives whose accumulation in the body leads to secondary symptoms.

Treatment is done in the following ways –

1. Cholesterol supplementation – this is done by supplementing cholesterol in the diet of the patient. The supplementation starts at a dose of around 40-50 mg/kg/day and then increased gradually according to the needs of the patient. This is overviewed either through foods like egg and cream that have a high cholesterol content or purified food grade cholesterol. Tube feeding may be needed for infants and younger children.
2. Simvastatin therapy – unlike cholesterol, simvastatin can cross the blood-brain barrier and this is a huge advantage. It is an inhibitor of HMG-COA reductase and have shown to decrease the levels of 7DHC in the body, and have also shown to increase the levels of cholesterol. It has also reported increasing the expression of genes involved in cholesterol synthesis and uptake.
3. Antioxidant supplementation – a recently discovered approach for treating Smith Lemli Opitz Syndrome is by antioxidants. This is still under trial. Vitamin E has come out to be the most effective antioxidant to treat the disease as they have significantly reduced the levels of oxysterols in the brain of mouse models. The clinical significance and the negative effects on the human body of this treatment are still unknown.

Smith Lemli Opitz Syndrome can be detected at an early age as well as at a matured age. If the nature of the disease involves symptoms that are not so severe and involves the gastrointestinal disorders, eye disorders, and so on, they can be treated by cholesterol supplementation and simvastatin therapy. But patients with severe conditions like heart defects, genital anomalies, and dislocated cleft palates need surgeries. Cholesterol supplementation in combination with simvastatin therapy is used to combat the disease in patients who show early symptoms of the disease.

Patients who are already suffering from liver disorders cannot be treated with simvastatin therapy because this can further damage their livers. Patients who are suffering from the severe form of the Smith Lemli Opitz Syndrome have to undergo surgery as the only option because their bodies are too weak to respond to the drugs. Though cholesterol supplementation treatment can be used, simvastatin therapy has to be restricted in such cases. The management of individuals suffering from Smith Lemli Opitz Syndrome is very complex and should be done under a team of specialists. Good care also has to be taken of the infants and children who are diagnosed with this disease.

There have been no proven side effects for cholesterol supplementation treatment. But in some of the cases where simvastatin therapy was used, there has been a development of possible risk of liver damage, which is why this treatment has to be used in a careful manner providing support to the liver before and during the treatment. Dietary supplementation of cholesterol is now widely used in combination with simvastatin therapy but the treatment hasn't shown to have prolonged effects which is why antioxidant supplementation treatment is now widely being tested in laboratories to get a new long-lasting treatment.

There are some basic post-treatment guidelines to be followed in the case of Smith Lemli Opitz Syndrome. Basically, this is a genetic disorder, so the disease can never fully be cured. Those who suffer from the disease, especially children, need to be kept under supervision always. Depending on the severity of the syndrome, the patient should be kept away from stimulators. Most kids with Smith Lemli Opitz Syndrome display autistic tendencies, so they should be taken proper care of. The medication regime should be followed properly and in the case of a surgery, the wound should be allowed to heal properly. The degree of the disease is different in different individuals and accordingly, they should follow the post-treatment guidelines.

Smith Lemli Opitz Syndrome is a genetic disorder and children born with this syndrome have to carry the syndrome for their entire lives, depending on the severity of the syndrome. The existing cholesterol supplementation treatment isn't a long-term solution because studies have shown that the cholesterol levels begin to drop within two weeks of the stoppage of the treatment. The simvastatin therapy is more prolonged but has to be used properly to get satisfactory results. Apart from this, no other therapy has been discovered until now. Thus, there is no such mentioned recovery time of the disease and it depends completely on the individual and the extent of the disease.

Basically, the cholesterol supplementation treatment can be done with the help of easily available food products like eggs and cream. Purified cholesterol supplements are a little costly in India which each bottle costing about a thousand rupees ( Rs 1000). Simvastatin drugs are available in most of the drug stores. The formulation is marketed by many drug manufacturing companies like Cipla, Ranbaxy, Micro Labs, etc. All these drugs ( a set of ten capsules) are priced between Rs 50 to Rs 150. The number of capsules to be taken daily depends on the extent of the disease and the specialist treating the patient.

The results of cholesterol supplementation treatment are not permanent because cholesterol cannot cause the blood-brain barrier and thus the cholesterol levels begin to drop within two weeks of stoppage of the treatment. But simvastatin can cross the blood-brain barrier and thus acts in a more permanent way. But the problem is that there are many more complications related to this disease which makes it very difficult for one single drug to control the symptoms and conditions of the disease. But now cholesterol supplementation treatment is being used along with simvastatin therapy to control this disease to some extent.

As of now, there are no alternatives to the treatment. But research is underway to find out other treatments. One such treatment which is under clinical trial is the antioxidant supplementation treatment in which vitamin E is used as it is the most powerful antioxidant to treat Smith Lemli Opitz Syndrome. In the test mouse models, this therapy was able to reduce the levels of oxysterols in the brain. These oxysterols increase the toxicity levels of the body, so reducing them would lead to beneficial effects.