Introduction
Down’s syndrome: a brief history
John Langdon Down, whilst working at Earlswood Asylum for Idiots at Redhill in Surrey between 1859 and 1869, noticed that certain children had the same appearance and commented in his paper, Observations on an ethnic classification of idiots (1866) that “their resemblance to each other was such that, when placed side by side, it is difficult to believe that they are not the children of the same parents.” He described their physical features in a way which would be immediately recognisable to anyone involved with Down’s syndrome people today. This must have been an important first step in recognising that certain children were mentally retarded for the same reason, and that reason had a familial, that is genetic, basis. Down believed that these children were a ‘throw-back’ to a more ‘primitive’ race, specifically Mongolians, hence the term ‘mongolism’. It was not until 1965 that moves were made to rename the condition, when representatives of the Mongolian People’s Republic approached the World Health Organisation and requested of the Director General that the term be abandoned, and the condition thenceforth be known as Down’s syndrome.
The genetic cause of Down’s syndrome was finally discovered in 1959 by a French man, J. Lejeune. Down’s syndrome is the most common recognised chromosomal disorder found in humans, and falls into a category of chromosomal disruptions known as trisomies. This means that instead of there being two copies of a particular chromosome, there are three. When it is chromosome 21 of which there is an extra copy the condition is Trisomy 21, or Down’s syndrome. Chromosome 21 is the smallest human chromosome. This may explain why individuals with Trisomy 21 are the only trisomy individuals who survive beyond a few months. In fact most trisomies will cause foetuses to spontaneously abort. Trisomy 21 is found in three different chromosomal set-ups, known as karyotypes:
Standard Trisomy 21 appears to be the result of a fault of meiosis or mitosis in either a parental gamete or in the zygote, resulting in every single cell being trisomic. It appears that 90-98% of Down’s syndrome individuals are Standard Trisomic 21
If mutation occurs after the first cell division of the zygote two cell lines will form, those with the normal 46 chromosomes and those with the extra chromosome 21. Depending on when and where the mutation occurs, the trisomic cells can vary from very few to nearly 100%. This is known as Mosaic Trisomy 21 and is found in 2-5% of Down’s cases.
- In 3-5% of cases the individual does not have an additional chromosome because the long arm of the extra chromosome 21 has attached itself to another chromosome, Translocation Trisomy 21
It has been suggested that the extra chromosome results in a proportional increase in the expression of the genes represented on chromosome 21, resulting in an imbalance between the products determined by chromosome 21 and products determined by the genes on other chromosomes. This imbalance could be what produces the characteristic Down’s syndrome phenotype, but there is not yet evidence ruling out the existence of mutations on the other genes.
Restrictions on applying research findings
Despite the recognisable physical features which characterise Down’s syndrome individuals — broad, flat face, protruding tongue, small nose and mouth, distinctive epicanthal folds, and slanted eyes — there is considerably more variability in the presentation of features in Down’s syndrome than in the same features in the normal population. This means that the degree of mental retardation and of growth delay (for instance) will vary quite widely from individual to individual; it also means that research findings, especially from small samples, and particularly from individuals sharing a similar environment, should be applied to larger populations with great care.
When, in 1940, Dr Henry Turkel was approached by the father of a Down’s Syndrome child, and asked to treat his child, very little was known about the causes of Down’s Syndrome (DS). However, Dr Turkel did know that “all living cells require proper nutrients in optimal quantities for the specific cell to develop normally” (1974). His experience treating diabetes, allergies and arteriosclerosis, using what would now be known as an orthomolecular approach, was the foundation of his methodology. With the aim of “removal of the harmful expression of the genes by removing the accumulating metabolites” he created a series of medicines known as the U series. These were designed to have a “simultaneous and synergistic” (1963) effect. However, though he claimed considerable success in diminishing inborn structural, functional and chemical abnormalities and produced photographs and X-rays of his subjects as evidence, Dr Turkel never performed a controlled trial of his treatment.
Since then there have been other claims of success treating DS subjects with nutritional therapies but none that have been sustained (Sylvester, 1984). For instance, Harrell et al (1981) found that nutritional supplements were beneficial for DS children, affecting IQ, height, vision, appearance, and general achievement. However, attempts to replicate these results have failed so far (Weathers, 1984; Bennett et al, 1983; Smith, 1984), leading to disagreements on the letters pages of The Lancet (Sept. 1983) and The Journal of Paediatrics (March 1985).
Zinc and its links with Down's syndrome
This paper considers a single nutrient, zinc, and its place in supporting people with Down’s syndrome. The importance of zinc is suggested by the many disease states found in DS that have also been observed in subjects with zinc deficiency. These include diabetes mellitus, dwarfism, hypogonadism, atherosclerosis, vitamin A deficiency night blindness, cirrhosis of the liver, myeloid leukaemia (Milunsky, 1970), and hyperthyroidism and hypothyroidism (Napolitano et al, 1990). Fabris et al (1993) cite the importance of zinc in the homeostatic networks found to be altered in DS, namely nervous, neuroendocrine and immune, and their interrelationship, plus a reduced turnover of this mineral, leading to the hypothesis that zinc deficiency could be implicated in at least some of the DS phenotype.
“Zinc forms part of the composition of at least 160 different enzymes. Indeed, zinc is the most widely used mineral in enzymes” (Graham and Odent, 1986). It is vital for protein, essential fatty acid and carbohydrate metabolism, and for DNA synthesis, and can be used to detoxify lead and mercury (ibid.). The body only has a small pool of biologically available zinc, and a rapid turnover, meaning that deficiency signs appear very quickly (Passwater and Cranton, 1983).