What Is Toulouse-Lautrec Syndrome?
Toulouse-Lautrec syndrome (TLRS) is a rare genetic disorder characterized by the presence of two mutations in the gene encoding for the enzyme tyrosinase. TYROSINASE catalyzes the conversion of tryptophan into serotonin, which plays an essential role in mood regulation and sleep patterns. TLRS results from a single nucleotide polymorphism (SNP) located within exon 3 of the TYROSINASE gene. Mutations in this SNP result in either one or both copies of the mutated allele being expressed, resulting in abnormal expression of the tyrosine hydroxylase enzyme. The absence of the mutant allele results in normal levels of serotonin synthesis and action.
The mutation occurs only in individuals homozygous for the missense variant, while those with one copy have two copies of the missense variant. Individuals heterozygous for the missense variant show no significant difference in serotonin synthesis compared to persons homozygous for the wild type allele. In this case, the most common mutation results in a valine to a glutamate substitution at position 102 (Val102Glu), which is located within the catalytic domain of the enzyme.
The most severe symptoms of the disease are linked to alterations in dopaminergic activity. Abnormalities of dopaminergic signaling have been linked to several psychiatric conditions, including obsessive-compulsive disorder and Tourette’s syndrome.
The role of dopaminergic signaling in the development of tic disorders and obsessive-compulsive behavior has been well established. The most common symptom of the disease is Gilles de la Tourette syndrome, a disorder characterized by the presence of multiple vocal and motor tics. These symptoms are often accompanied by obsessive-compulsive features. In addition to these symptoms, patients with this syndrome have been noted to suffer from attention deficit hyperactivity disorder and personality changes.
Adults with this syndrome have been noted to have increased symptoms of depression, anxiety, and social avoidance. The intensity of tic symptoms begins to decline in adulthood. However, the frequency and persistence of obsessive-compulsive symptoms increase through adulthood.
Recent research has revealed that there may be key structural alterations in certain areas of the brain which are responsible for the behavioral and psychological aspects of this syndrome. These alterations are most prominent in the caudate nuclei and thalamus.
Research has also suggested that there may be an inverse relationship between the severity of obsessive-compulsive and attention deficit hyperactivity symptoms and the severity of tic symptoms.
While the exact role dopaminergic signaling plays in the behavioral aspects of this syndrome is still under investigation, studies have revealed dopaminergic abnormalities in patients with this condition. Dopamine agonists such as bromocriptine and pergolide have been shown to improve tic symptoms in adults, though they are not without their own side effects. The mechanism of action for these drugs is by binding to the dopamine receptors, in this case the D2 receptor.
Dysfunction within the dopaminergic system may be caused by several factors. Dopamine has been shown to play a role in modulating coordinated movement. Several studies have linked dopamine signaling defects to movement disorders. Research has also linked the degeneration of the dopaminergic system with aging.
The dopaminergic system is a sensitive target of the toxicity of heavy metals, such as lead and mercury. Exposure to these substances has been linked to the development of a wide range of neurological conditions, including Parkinson’s disease.
There is evidence that patients with Tourette syndrome suffer from more oxidative stress than the average person. Antioxidant nutrients such as Vitamin C have been shown to alleviate the frequency of tic symptoms in patients with this condition.
While more research is necessary to determine a possible genetic link between obsessive-compulsive disorder and Tourette syndrome, initial studies have revealed that there may be common factors involved in the pathology of both of these conditions.
While the exact cause of Tourette syndrome remains unknown, research from a variety of fields has shed some light on possible mechanisms involved in the development of this condition.
Research has revealed that tic symptoms are not a result of voluntary actions. Rather, tics are caused by a “release” phenomenon where built-up tension must be released in the same way that one would release pressure that has built up in a tightly sealed bottle. While the exact causes of this tension are not known, there are theories that involve both biological and environmental factors.
One theory involves the brain structures and pathways involved in regulating fundamental human behaviors such as speech, movement, and breathing. The exact nature of certain neurological processes involved in these behaviors are still not fully understood by scientists, but studies have revealed abnormalities in some of the structures and pathways that regulate these functions.
Research has also linked abnormalities in the dopaminergic system with the development of movement disorders such as tremor, rigidity, bradykinesia, and postural instability. While these conditions are more commonly associated with degenerative illnesses such as Parkinson’s disease, studies have revealed that people suffering from Tourette syndrome have also had high levels of dopamine.
A possible theory involves a phenomenon known as the “toxic siege”. This theory states that heavy metal poisoning, such as exposure to lead or mercury, can trigger a build-up of toxic substances within the body. These substances damage or destroy cellular systems within the body. While the body is capable of repairing some of the damage, it may not be able to keep up with the demand created by the presence of these foreign substances.
The symptoms of Tourette syndrome represent the body’s unsuccessful attempt to repair itself. The links between heavy metal poisoning and Tourette’s syndrome are still not fully understood, however.
Sources & references used in this article:
Toulouse Lautrec Syndrome by H de Toulouse Lautrec – syndromespedia.com
Pycnodysostosis with unusual findings: a case report by Q Mujawar, R Naganoor, H Patil, AN Thobbi, S Ukkali… – Cases Journal, 2009 – Springer
Pycnodysostosis: the disease of Henri de Toulouse-Lautrec by K Markatos, AF Mavrogenis, M Karamanou… – European Journal of …, 2018 – Springer
Henri de Toulouse-Lautrec by H de Toulouse-Lautrec, D Cooper – 1952 – thereaderwiki.com
recently described cathepsin I leading to pycnodysostosis (e Toulouse-Lautrec) was too late by W Mason – researchgate.net