WHAT: Genetic faults in Autism include abnormalities of a pathway that uses the Sulfate radical in carrying out a number of metabolic functions. WHERE: Sulfation works at many tissue levels, but by far the most important seems to be its waste and toxin excretory functions in the liver.
Homocysteine is a problematic amino acid. It is either converted to methionine by Vitamin MB12 to transport the Methyl fraction to brain and nerves (Refer Methylation pathways) or to Glutathione with the help of Pyridoxine or its derivatives (P5P), and some vital enzymes. Deficiency of Pyridoxine or necessary enzymes to metabolise Homocysteine to useful chemicals like Glutatione causes the problems of Sulfation pathways.
Glutathione is the most important cleansing systen of the body for getting rid of excessive oxidation causing chemicals, waste and toxic matter. The effects of its deficiency can therefore be well imagined.
As per Meister A, Anderson ME, “Glutathione,” 1983, Annual Reviews in Biochemistry, 52, 711-760
Glutathione functions in the protection of mammalian cells against the effects of radiation, oxidative damage, and certain toxic compounds of endogenous and exogenous origin.Recent studies have shown that cellular protection may be enhanced by increasing the levels of glutathione
Reduced L-glutathione is chemically ?-glutamyl-cysteinyl-glycine. It is also more popularly known as GSH. It's deficiency increases oxidative stress, which has an important role to play in aging. It is also a contributor of the pathgology behind many diseases, with some of the more common ones being seizure, Alzheimer’s disease, Parkinson’s disease, liver disease, cancer, heart attack, stroke, diabetes and Neurodevelopmental disorders like Autism and perhaps Down's syndrome also.
OTHER PROBLEMS IN SULFATION PATHWAYS
The section below is adapted from:: Sulphation and Autism: What are the links?
Rosemary H. Waring , School of Biosciences, University of Birmingham, Birmingham B15 2TT U.K.
GENETICS
Reduced sulfation prior to excretion is seen in autistic children who were challenged with a paediatric dose of paracetamol. They were less able to form its sulphated derivative than controls of the same age although the glucuronidation pathway was unaffected.
The first stage in this process involves the enzyme cysteine dioxygenase (CDO); cysteine sulphinic acid is formed and undergoes fission to provide sulphite (SO 3 2- ) ions which are then further oxidised to sulphate (SO 4 2- ) ions by the enzyme sulphite oxidase (SOX). Obviously, if CDO or SOX have reduced activity, the provision of sulphate will also be decreased. The human CDO gene is localised to chromosome 5 (5q22-23) and it is interesting that analysis of 110 multiplex families with autism, where one sibling had autism and the other a diagnosis of Asperger's syndrome or pervasive developmental disorder, suggested linkage on chromosomes 5 and 19 while a study on ADHD (attention deficit/hyperactivity disorder) found a linkage to chromosome 5q33.
ACTION IN BRAIN
There is localisation of the CDO protein in the CNS, being particularly found in the cerebellum and the Purkinje neurons; these are known to be abnormal in patients with autistic spectrum disorders.
Sulphation is a major inactivation pathway for adrenaline and allied neurotransmitters such as the dopamine, about 80% of which is sulphated in man. Usually, when chemical neurotransmitters are released in the central nervous system, they act at receptor proteins and are then inactivated by sulphation or by FAD-linked mono-oxygenases or alternatively are carried by transporter proteins back into the initiating neurone. Failure of a major pathway such as sulphation will lead to a neurotransmitter imbalance and raised serum and CSF levels of dopamine and elevated urinary levels of dopamine metabolites have been found in autistic children.
BRAIN FORMATION
Sulphation also affects the synthesis of brain tissue. Sulphated polysaccharides and glycosaminoglycans are so important in the development of the foetal and neonatal brain that any alteration in their structure may have serious consequences - it is currently thought that these compounds act as 'scaffolding' to direct the direction and 'wiring' of brain neurons. Sulphate transport across the placenta increases dramatically around the time of birth when most of the glial cells are being formed and these increased levels of sulphate are associated with formation of astrocytes and oligodendrocytes from progenitor.
REMEDY
Enhance Glutathione production by the liver by giving proper dose of its raw materials and conversion helping chemicals (available)
Glutathione supplementation may also be given..
Enhance Glutathion's life in side the body by adding supplements that take over the burden of Free Radicals from it, leaving it to fight again
TREATMENT OPTION
Contact Dr. Mukherjee. Also, SKYPE consultation available for international and outstation parents of children with autism spectrum and other NDDs, by prior appointment through E-mail and transfer of consultation charges to designated bank account as will be informed on E-mail.
This is just a brief write-up. Much more can be done to help children with Autism or allied disorders with metabolic or genetic or pollution aggravated NDDs.
TREATMENT OPTION
Contact Dr. Mukherjee. Also, SKYPE consultation available for international and outstation parents of children with autism spectrum and other NDDs, by prior appointment through E-mail and transfer of consultation charges to designated bank account as will be informed on E-mail.
