By Teresa Conrick
In Part 1 (HERE), we learned that Autism appears to have a melanin connection with Parkinson's, Amyotrophic Lateral Sclerosis, Alzheimer's, Melanoma, Tourette's, Dystonia and Schizophrenia. Melanin appears to be lacking or not functioning properly thus causing quite possibly, the motor disturbances and/or neurodegeneration that is shared among these increasingly diagnosed diseases. This may happen as those who have poor melanin then lack the ability to detoxify , ie -"the resulting melanic component serves an additional protective role through its ability to chelate and accumulate metals, including environmentally toxic metals such as mercury and lead.." HERE
decided to investigate more about autism and this melanin connection. Though I have been in the autism world almost 15 years since Megan was diagnosed, some of this information was new to me and some I knew a little about but have learned much more. Looking up "melanin" and "autism" together brought me to these disorders:
3-Hypomelanosis of Ito
There may be more but for the sake of making a point, I will focus on these. Notice there is a pattern of hypomelanin and autism in each.
"When the OCA2 gene is also deleted from chromosome 15, a person with Angelman syndrome is likely to have light-colored hair and skin, compared to family members. This occurs because the OCA2 gene controls the protein that produces the pigment melanin, which provides color to hair, skin and eyes. Most cases of Angelman syndrome occur even though there is no history of the disorder in the patient’s family. The syndrome often is a result of a random genetic mutation that occurs during the formation of cells early in embryonic development. The cause remains unknown in about 10 to 15 percent of Angelman syndrome cases. Angelman syndrome affects all genders, races and ethnic groups. However, the vast majority of cases in the United States involve Caucasians, according to the Angelman Syndrome Foundation." HERE
Similar to autism, individuals with Angelman Syndrome display the following behaviors: hand-flapping, little or no speech, attention deficits, hyperactivity, feeding and sleeping problems, and delays in motor development. These individuals may also engage in biting and hair pulling. Many tend to have a stiff-legged gait and jerky body movements. "
Angelman Syndrome HERE
Key Points: random genetic mutation (another way of saying there is not a reason and they do not know why), light-colored hair and skin
"Cutaneous and ocular pigmentation were evaluated in 29 individuals with the Prader-Willi syndrome (PWS). Criteria for hypopigmentation included the presence of type I or II skin, the lightest skin type in the family by history, and iris translucency on globe transillumination. On the basis of these criteria, 48% of the PWS individuals were hypopigmented. The presence of hypopigmentation correlated with a small interstitial deletion on the proximal long arm of chromosome 15; however, this deletion was also found in individuals who did not meet the full criteria for hypopigmentation. Hairbulb tyrosinase activity and glutathione content, as well as urine cysteinyldopa excretion, were low in PWS individuals with and without hypopigmentation and did not separate these two groups. We conclude that hypopigmentation is found in a significant proportion of individuals with PWS and that the hypopigmentation may be associated with a deletion of the long arm of chromosome 15. The mechanism for the hypopigmentation is unknown."
Hypopigmentation in the Prader-Willi Syndrome HERE
In addition to a well-described behavioral phenotype that includes hyperphagia, obsessive-compulsive symptoms, disruptive behavior, and an increased risk for mood disorders, recent evidence also suggests that some individuals with PWS have repetitive behavior and social deficits reminiscent of autism spectrum disorders."
Autistic-like symptomatology in Prader-Willi syndrome: A review of recent findings HERE
Key Points: hypopigmentation, mechanism for the hypopigmentation is unknown, lightest skin type in the family by history, deletion was also found in individuals who did not meet the full criteria for hypopigmentation.
Hypomelanosis of Ito
"Hypomelanosis of Ito (HI) is a syndrome with hypopigmented whorls of skin along the Blascho lines. The old name, Incontinentia pigmentosa achromiance was probably used because HI appears to be the negative image of incontinentia pigmentosa. This disorder is inherited as an autosomal – dominant trait with variable penetrance and the implicated genes are 9q33 and q11-13, Xp11. Chromosomal mosaiscm is believed to be the reason that hypomelanosis of Ito is so varied in phenotype. Hypopigmented skin lesions appear as whorls or streaks on any part of body and tend to progress onto uninvolved areas. The cutaneous lesion is often associated with developmental and neurological abnormalities. Pyramidal tract dysfunction, mental retardation and seizures are common neurological signs. Ophtalmologic disorders are also present."
A rare case of hypomelanosis of ITO HERE
"Hypomelanosis of ito is frequently associated with autism"
"Twenty-five children with hypomelanosis of Ito are reported: 10 of them had autism, 3 showed autistic-like features, 1 had previously shown autistic features which had subsequently faded, 2 had disintegrative psychosis. The 9 remaining children were all mentally retarded and 5 of them were more markedly retarded in their speech development. The hypothesis is considered that a dysfunction of *melatonin (* Translation error- this should be "melanin" - HERE) may favour the development of both skin depigmentation and autistic behaviour through an altered production of corticotrophin-releasing hormone and, in turn, of proopiomelanocortin. HERE
"Two girls and a boy showing autistic behaviour and fulfilling the criteria for autistic disorder, Asperger syndrome or atypical autism were diagnosed as having hypomelanosis of Ito syndrome. It is suggested that skin changes indicating underlying neurocutaneous disorders be meticulously looked for in all cases with autism and autistic-like conditions." "Hypomelanosis of Ito in three cases with autism and autistic-like conditions." HERE
Key Points: hypopigmented whorls of skin, cutaneous lesion is often associated with developmental and neurological abnormalities
"Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed:..... mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron.." "Neuropathology of Rett syndrome " HERE
Key Points: underpigmentation of the zona compacta nigrae, fewer melanin granules
We will focus on lipofuscin later.
"About 50% of people with TSC have learning difficulties ranging from mild to significant, and studies have reported that between 25% and 61% of affected individuals meet the diagnostic criteria for autism, with an even higher proportion showing features of a broader pervasive developmental disorder. A 2008 study reported self-injurious behavior in 10% of people with TSC. Other conditions, such as ADHD, aggression, behavioral outbursts and OCD can also occur. Lower IQ is associated with more brain involvement on MRI."
"Some form of dermatological sign will be present in 96% of individuals with TSC. Most cause no problems but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include:
• Facial angiofibromas ( "adenoma sebaceum"): A rash of reddish spots or bumps, which appear on the nose and cheeks in a butterfly distribution. They consist of blood vessels and fibrous tissue. This socially embarrassing rash starts to appear during childhood and can be removed using dermabrasion or laser treatment.
• Ungual or subungual fibromas: Also known as Koenen's tumors, these are small fleshy tumors that grow around and under the toenails or fingernails and may need to be surgically removed if they enlarge or cause bleeding. These are very rare in childhood but common by middle age.
• Hypomelanic macules ("ash leaf spots"): White or lighter patches of skin that may appear anywhere on the body and are caused by a lack of melanin. These are usually the only visible sign of TSC at birth. In fair-skinned individuals a Wood's lamp (ultraviolet light) may be required to see them.
• Forehead plaques: Raised, discolored areas on the forehead.
• Shagreen patches: Areas of thick leathery skin that are dimpled like an orange peel, usually found on the lower back or nape of the neck.
• Other skin features are not unique to individuals with TSC, including molluscum fibrosum or skin tags, which typically occur across the back of the neck and shoulders, ''café au lait'' spots or flat brown marks, and poliosis, a tuft or patch of white hair on the scalp or eyelids." "Tuberous Sclerosis Symptoms" HERE
Key Points: Hypomelanic macules, lack of melanin, "cafe au lait" spots
"A 6-year-old male with apparently isolated mental delay, speech delay, attention deficit/hyperactivity disorder, epilepsy, and subtle and insignificant skin dyschromias. Investigators ruled out genetic syndromes, congenital infections, fetal deprivation, perinatal insults, intrauterine exposure to drug abuse, and postnatal events such as CNS infections as possible common causes of brain impairment. Being all further test negative, the patient exhibited an ultrastructural defect of the skin, identical to that previously described [Buoni S, Zannolli R, de Santi MM, Macucci F, Hayek J, Orsi A et al. Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vesicular trafficking and melanosome defects. Eur J Neurol 2006;13:842-51], suggesting that some cell compartments, such as rough endoplasmic reticulum, lysosomes, Golgi apparatus, and the vesicular zone (racket) of Birbeck granules, sharing similar components, can be altered, resulting in a common defect in cell trafficking, associated to melanosome defects."
Key Points: ruled out genetic syndromes etc, defect in cell trafficking associated to melanosome defects
This pattern made me continue to look and question how this could happen. Reading up on melanin, I saw that tyrosine was a precursor to melanin production, associated with melanosomes. That flung open all new doors and like my fellow writer at Age of Autism, Adriana Gamondes, mercury was popping up with melanin.
The skin lightening issue of mercury definitely included my investigations of melanin and these neurodegenerative disorders. I found this one first and it got my interest:
"In the present study, we investigated the dermal absorption of mercury and its accumulation in the tissues of albino and pigmented mice treated with two brands of mercury containing skin-lightening creams for a period of one months at different intervals. Mercury levels were measured in a total of 133 and 144 liver, kidney and brain tissue samples of albino and pigmented mice. Significant differences in the mercury levels were observed between the albino and pigmented mice. This emphasizes the protective role of melanin against mercury toxicity." "Comparison of mercury levels in various tissues of albino and pigmented mice treated with two different brands of mercury skin-lightening creams." HERE
It got more interesting:
"Inorganic mercury compounds are also widely used in skin-lightening soaps and creams, due to the ability of the mercury cation to block the production of melanin pigment in the skin." "Elemental Mercury And Inorganic Mercury Compounds: Human Health Aspects"
And More specific:
"The pharmacologic activity of the skin-light-eners occurs as the mercury blocks the production of melanin pigment in the epithelial melanocytes, thus lightening the skin over time." "Inorganic: the other mercury." HERE
As Adriana reported, even the Chicago Tribune, not a fan of mercury causing autism, reported the same thing:
"Mercury, a known toxin, is banned in skin-bleaching or lightening creams. The products are used to lighten complexions, eliminate age spots or diminish freckles. Mercury is sometimes illegally added to creams because the metal blocks production of melanin, which gives skin its pigmentation. Mercury is rapidly absorbed through the skin and can cause severe health effects, including neurological and kidney damage." "FDA widens mercury-skin lightening cream investigation" HERE
So then I decided to investigate this phenomenon in other species:
"Ovigerous females of the estuarine crab Chasmagnathus granulatus were exposed to mercury (0.1 mg/L) during the entire, early, or late embryonic development. Particularly, hypopigmentation of body chromatophores was the abnormality that showed the highest incidence, this incidence being greater when ovigerous females were exposed to mercury either during the totality or just the first half of the egg incubation period. In contrast, the effect of mercury on the morphology and pigmentation of eyes was greater when the exposure comprised the totality or just the second half of the incubation period. These results correlate with the timing of both body pigment synthesis and eye formation during embryonic development. Although these abnormalities have been observed in the same species with other heavy metals, such as zinc and copper, the responsiveness during the early and late embryonic development was different with mercury." "Toxicity of mercury during the embryonic development of Chasmagnathus granulatus (Brachyura, Varunidae) HERE
Could flu shots with thimerosal act in this same manner or what about living near a coal fired power plant?
"Heavy metals (As, Cd, Cu, Hg, Se, Zn) were shown to increase the incidence of albinism. Metal-induced albinism resulted from exposure of both adult fish and eggs." "Accelerated Rate of Albinism in Channel Catfish Exposed to Metals" HERE
Albinism was the extreme version of hypomelanin so I thought that might show a clue:
"Oculocutaneous albinism is a hypomelanotic skin disorder. Oculocutaneous albinism is infrequently reported in association with childhood autism when compared to tuberous sclerosis and hypomelanosis of Ito. However, Rogawski et al  had reported co-morbidity of oculocutaneous albinism and childhood autism in two boys and Delong  in a recent description of families of individuals with childhood autism had noted additional feature of oculocutaneous albinism in some families in addition to major affective disorder and special talents. Going by the observation of this present case report and the report of these two previous reports in the literature [11,12], the question arises whether childhood autism has any genetic and clinical relationship with oculocutaneous albinism. "Childhood autism in a 13 year old boy with oculocutaneous albinism: a case report" HERE
This study on albinism really interested me as these were not babies born with autism:
"2 tyrosinase-positive albino boys, 1 Caucasian and 1 American Negro, manifested moderate retardation and autistic behaviour. It is postulated that the as yet unidentified metabolic defect in albinism may be responsible for the CNS disorder in these 2 boys."
"Oculocutaneous Albinism and Mental Disorder A Report of Two Autistic Boys" HERE
Well, Yale dropped the ball as that was in 1978 and I have not seen anything since on melanin-autism from Yale. How is it that 2 boys "manifest", kind of like regress, into autism, both having zero melanin, and not one researcher since thought that was significant?
"Oculocutaneous Albinism and Mental Disorder A Report of Two Autistic Boys"
At this point, I want to bring up that word, lipofuscin. It came up when looking at the autopsies of the girls who had Rett's diagnoses. I saved it until now as it needed to be place in a certain manner and this is a good spot. I did gasp when I looked it up initially on Wikipedia:
"Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It appears to be the product of the oxidation of unstaurated fatty acids and may be symptomatic of membrane damage, or damage to mitochondria and lysosomes. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury, aluminum, iron, copper and zinc."
So here was another pigment, which also looked to scavenge metals, being found in autopsied bodies of those with an autism diagnosis. Investigating this more found these:
"Impaired language function is a principle criterion for the diagnosis of autism. The present study of brain from age-matched autistic and control subjects compared brain regions associated with the production and processing of speech. Striking differences in the density of glial cells, the density of neurons and the number of lipofuscin containing neurons were observed in the autistic group compared with the control group. The autistic group exhibited significantly greater numbers of lipofuscin-containing cells in area 22 (p<0.001) and area 39 (p<0.01). The results are consistent with accelerated neuronal death in association with gliosis and lipofuscin accumulation in autism after age seven. Production of lipofuscin (a matrix of oxidized lipid and cross-linked protein more commonly associated with neurodegenerative disease) is accelerated under conditions of oxidative stress."
"A Microscopic Study of Language-Related Cortex in Autism" HERE
That seemed very significant. I like Wikipedia but thought I needed more verification on what lipofuscin was so again looked for more:
"The objective of our study was to investigate the toxic effects of mercury on northern pike. Liver color (absorbance at 400 nm) varied among northern pike and was positively related to liver total mercury concentration. The pigment causing variation in liver color was identified as lipofuscin, which results from lipid peroxidation of membranous organelles. An analysis of covariance revealed lipofuscin accumulation was primarily associated with mercury exposure, and this association obscured any normal accumulation from aging. We also documented decreased lipid reserves in livers and poor condition factors of northern pike with high liver total mercury concentrations."
"Mercury toxicity in livers of northern pike (Esox lucius lucius) from Isle Royale, USA" HERE
"Eighteen stranded Atlantic bottlenose dolphins (Tursiops truncatus) examined postmortem were sampled for histologic study. All cases were examined for ferric ion and lipofuscin. Chemical analysis for mercury was conducted on 12 of the animals by atomic absorption spectrophotometry. Nine animals were found to have excessive lipofuscin in both liver and kidney. The evidence suggests that the excessive pigment accumulation is related to toxic effects of Hg and presents as increased active liver disease. "Liver abnormalities associated with chronic mercury accumulation in stranded Atlantic bottlenose dolphins." HERE
and this convinced me as well:
"A male subject became exposed to metallic mercury vapor at work in 1973. He never returned to work again and died of lung cancer in 1990. Ultrastructurally mercury could be demonstrated by elemental x-ray analysis within lipofuscin deposits. The lipofuscin content was increased in the mercury positive nerve cells as demonstrated by a strong positive autofluorescence." "Demonstration of mercury in the human brain and other organs 17 years after metallic mercury exposure." HERE
At this point, I need to say that there is more but my point, I hope, is made that research in this area is deplorably LACKING and children are SUFFERING as a result. We have seen melanin is deficient in many children receiving an autism diagnosis as well as an increase in another type of pigment, strongly suggestive of mercury exposure in both instances. Genes do not even come close to explaining this. True research into environmental causes, especially mercury, needs to be done. Dan Olmsted and Mark Blaxill's book, "The Age of Autism: Mercury, Medicine, and a Manmade Epidemic," will do much to educate on this denied and disturbing issue. I'll leave you with one more study. This one I could not find anything other than the title. I did try contacting the authors but to no avail. It looks like it could have been a warning sign but again, no one noticed.
Med J Aust. 1972 Dec 30;2(27):1484-6.
Melanin in the ascending reticular activating system and its possible relationship to autism. Happy,R Collins,JK
PMID: 4655127 [PubMed - indexed for MEDLINE]
Teresa Conrick is Contributing Editor for Age of Autism.