DO NOT SEEK AN ISLAND, I SHOW YOU A COMMUNITY.....Acromatopsia (The Colour Blind)

A couple of days ago I turned 57, which encoura ged me sending this article I have been preparing carefully but at the same time with the intention of making this subject known in order to find the best way to provide support to this Community

From here my thanks to my co-worker and friend César Delgado who provided me with very relevant information in relation to the ethnic characteristics of this population ...... thank you old man !!!....My Pingelap Island contacts know exactly what I mean; To them an acknowledgment to know how to face the day to day with this genetic disorder with which they have learned to live

DO NOT SEEK AN ISLAND, SHOW YOU A COMMUNITY

About 10 years ago I received a 24-year-old female, 26-week pregnant woman who required an Obstetric Ultrasound for control; Came on river boat accompanied by a Doctor from the near Health Center  where she had stayed for a few days but came from the Native Community of Sababantiari.

I entered the office and found the patient lying on the bed, waiting for the procedure.

At the end of the Ultrasound in which there wasn`t any alteration of the Gestation, I indicated to her that she could get off the table; At that moment, she struck herself against me; for this reason I asked the doctor if the patient had any visual difficulties.

The answer that the doctor gave me originated one of the most shocking moments that generated this story that I delayed in writing.

¨Precisely she does not see by day like many other residents of her community¨, that was the answer of the attending doctor !!!.

She told me that, like her, there were other people in the community who did not see during the day, who preferred not to leave their houses until nightfall but if they had to, they walked kicking the stones to orient themselves, but at night they were Great hunters.

Of course, as the Doctor elaborated on the description, my interest in the subject was growing.

One of the additional comments was that it was precisely a closed Matsiguenga or Machiguenga-Nanti Community in which marriage between blood relatives was permitted; It was not uncommon for two cousins or brothers to marry; An additional example was the custom of mourning in the case of 2 siblings in which one of them loses his wife; The custom indicates that the brother whose wife lives, surrender to the widowed brother to accompany him and comfort him during the stage of mourning and that if this woman becomes pregnant, the husband assumes the upbringing of the child as his own and the wife returns to live with the.

Extremely admired by this finding and by the story I said goodbye to the Physician to whom I requested the list of people who suffered from this rare type of blindness of which I had no prior knowledge.

This relationship was sent to me in 1 month.

One of the wonders of working in the jungle is to maintain direct contact with nature and within that, appreciate the various multicolored vegetation nearby, as well as the colorful variety of birds and some mammals in the area ......... I quickly understand That the people of Sababantiari do not have that privilege and that perhaps for decades they have lived thus and they must be accustomed to it.

Being an admirer of scientific knowledge, he believes that all medical advances must always be widespread, but also with several fixed questions in my mind:

What to do to improve the quality of life of the people who had the defect ?; Would there be any alternative? Some cure ?, some way to avoid a greater number of cases ?, I went to propose the study of this Native Community looking for the cause, which was rejected since it would originate a greater flow and entrance to the Native Communities to which we treat To protect, from outsiders to the operation leading perhaps to a greater impact than previously planned.

Today I no longer count on that relationship of people; I have searched for it many times and I have not found it again; However the patient returned to my Unit for another health issue; The reunion with her and her Pathology made me return to interest and concern for this case.

At first glance the pregnant woman showed difficulty in keeping her eyes open, blinking almost closing her eyes, forcing her eyesight from the fluorescent light of the clinic, which is known as photophobia and an involuntary lateral movement of both eyes or horizontal nystagmus.

It has been 10 years since that meeting and as I stated earlier, at that time I got a negative response in trying to arouse sufficient interest by following the group of patients affected by this visual disorder, which also somehow forced me to leave Aside the same interest. However, life has its paths and one follows them or avoids them in so far as it advances; Precisely because of these hazards of life a few weeks ago I asked for an opinion and authorization to return to their Native Community by sending me medical information of a patient that we had transferred to Lima in December for multiple burns, caused by his father, who threw boiling water "as Punishment for being too restless and for their bad behavior "(custom that is still in this area). Having been favorable the evolution of the patient from December to the first days of April, I authorized his return.

The following week, when I returned to my room, I saw two children from the Native Communities accompanied by their Mothers in the waiting area for river boarding, recognizing one of them who was about 45 days old, the group of the Medical Unit Donated blood due to a severe Anemia that required stabilization before being evacuated to Lima. When I talked to both ladies, I recognized the Mrs. who had attended the Obstetric Ultrasound for 10 years ...... and I recognized it precisely because of the closing of the eyelids trying to avoid the light .... it was her !!.

The burned child was his son, who was extremely restless, but he looked healthy, ran, jumped, laughed, sang, shouted with happiness; Fortunately the burn backs are insignificant.

When I spoke with her. I learned that most of the group of patients with the same visual difficulty of their community had died, leaving only 4 of them and these were 2 (male and female) of his 5 children, his father-in-law and her......In the video you can observe the Lady who is sitting who presents Fotofobia or difficulty to see the light of day.

The presence of this patient encouraged me to review the corresponding medical literature and I found precisely the term Acromatopsia or Syndrome of Dysfunction of Cones or Color Blindness.

As a result of the review of geographic information and contrast with that of the inhabitants of nearby areas, I found that Sababantiari is a populated center located on the banks of the Ticumpinia River, a tributary of the Urubamba, approximately 1 hour north west of the CCNN Timpía towards ¨¨Pongo de Mainique¨, In the Territorial Reserve Kugapakori Nahua Nanti Limit′s , in the Protected Natural Area of Megantoni and adjacent with Settlers of Rural Settlement Kitaparay.

About 25 Arahuac families live in Sababantiari with a total of 120 people, they speak the Matsiguengas and Nanti languages.

In the lower boundary of the attached Map they can identify the locality of Sababantiari; For this reason it is difficult access to the locality (since it is necessary to navigate in a tributary of the Low River Urubamba).

Precisely for being a reserve zone, protected by the State in which like the Kugapakori Nahua Nanti reserve, access is restricted by Legal Norms; So even the Ministry of Health team is only authorized to enter 4 times a year, that is one of the reasons why we have not seen many patients from that population center in our Medical Unit.

Acromatopsia is a non-progressive and hereditary vision disorder characterized by a decrease in visual acuity, sensitivity to light, and absence of color vision. In the United States, for example, Acromatopsia affects approximately 1 in 33,000 people.

Occasionally, Acromatopsia is called "daytime blindness" because these children see better in dimly lit environments. Children with complete Acromatopsia have a reduced vision (20/200 or less) due to an abnormality in their retina and as previously mentioned, these patients also have no color vision. Additionally they have sensitivity to light (photophobia) and Nystagmus (abnormal movement of the eyes), all these symptoms were presented by our patient.

Children who have partial achromatopsia may have better vision (20/120 to 20/80).

Globally, this condition affects approximately 1 in 40,000 live births. Its prevalence varies in different parts of the world. Because it has a genetic origin, it is more common in religions where there is an increased rate of marriages between relatives. It is also more frequent in Pingelap (islands located in the Pacific).

Acromatopsia should not be confused with red-green blindness, which is very common and affects 8% of all men. People with Red-Green Blindness have normal visual acuity and do not have a lack of full color perception.

Acromatopsia is caused by an abnormality of the retina, the portion of the eye responsible for "shaping the image". It is analogous to the roll of a camera. In the retina there are 2 types of cells: the Cones that allow to visualize the colors and therefore the vision of day and the Canes that allow the night vision.

In the group of Cones there are 3 three types of them: red cones, green cones and blue cones. There is a balance in the distribution of these cells, which is necessary to have a normal vision of colors. A child born with a complete limitation on the functionality of the cones will have Acromatopsia. Acromatopsia is a hereditary condition and so far we have found 5 genes involved (genetic markers found on chromosomes) and associated with this condition. The 4 chromosomes that have changes associated with Acromatopsia are: Chromosome 14, Chromosome 8q21-q22, Chromosome 2q11 and Chromosome 10q24.

The five genes are (GNAT2 (1p13), PDE6C (10q24), PDE6H (12p13), CNGA3 (2q11.2) and CNGB3 8q21.3), and all of them encode fundamental components of the phototransduction cascade of the cones (GNAT2 Protein G)> phosphodiesterase PDE6C / PDE6H> cyclic nucleotide-activated channel CNGA3 / CNGB3). Mutations in CNGB3 are predominant, followed by CNGA3 mutations, while the rest are rare causative agents of ACHM.

CNGA {3} protein: cyclic nucleotide cation channel, Alpha 3; CNGB3 [605080], protein: cyclic gateductoid cation channel, Beta 3; GNAT2 [139340], protein: guanine nucleotide binding protein, Polypeptide of alpha 2 transducing activity; PDE6C [600827], protein: 6C phosphodiesterase, specific cGMP, Alpha-prime cone; PDE6H [601190], protein: 6 H phosphodiesterase, specific cGMP, spectrum

Human Gene CNGA3 This gene encodes a member of the nucleotide-gated cyclic cation channel family of proteins that is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (monochrome of rod) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [Provided by RefSeq, Jul 2008

DESCRIPTION: Cyclic cationic channel of cationic channel alpha 3 (CNG channel alpha 3) (CNG-3) (cyclic channel nucleotide-alpha channel 3) (Cone photoreceptor cGMP-channel channel alpha subunit).

FUNCTION: Transduction of visual signals is mediated by a cascade coupled to G protein using cGMP as the second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thus causing a depolarization of cone photoreceptors. A blinking channel gating was induced, weakening rectification outwardly in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem, and improved cAMP efficacy of the channel when coexpressed with CNGB3 (by similarity). Essential for the generation of electrical responses evoked by light in sensitive red, green and blue cones.

SUBUNIT: Heteroligomeric Complex with CNGB3.

SUBCULAR LOCATION: Membrane; Multipass membrane protein.

SPECIFICITY OF THE TISSUE: Prominently expressed in the retina.

DISEASE: Defects in CNGA3 are a cause of achromatopsia 2 (ACHM2) [MIM: 216900]; Also known as total colorblindness or stem monocromacy (RMCH2). ACHM2 is an autosomal recessive condition characterized by day blindness and photophobia. In patients with ACHM2 cones are defective and subjects see better at night.

The gene of Acromatopsia is inherited both from the father and the mother, who carry the diseased gene on one of the chromosomes. Parents do not develop the disease because the two genes on the chromosome pair are required for an individual to be affected (autosomal recessive inheritance). This gives the family a 25% chance of an affected child (1 in 4) at each pregnancy. There will also be a 50% chance of having an unaffected child who is a carrier of the gene.

Characteristics of hereditary autosomal recessive diseases:

1- Affect with equal number of probabilities to males and females.

2- To appear the symptoms of the disease must be defective the two copies of the gene that causes ataxia.

3 - The so-called carriers carry a single defective copy of the disease gene and are generally normal and healthy individuals (they do not exhibit symptoms), but can transmit to their children the mutated gene that causes the disease. And they could even have an affected child if there was a combination with another defective copy of the other parent's gene.

If both parents are carriers of the defective gene, the probability that each of their children will inherit two copies of the defective gene and develop the disease is Of 25 percent.

5- If only one of the parents is a carrier, the probability of having affected children, except point mutations, is zero, while the one of having children carriers is of 50 percent and the one of having healthy children non-carriers is of another 50 percent.

6- With both parents carriers, the theoretical possibility that their children are carriers, such as parents, is 50 percent, while there is a 25 percent risk for children affected by the disease, and another 25 percent to, fortunately , Neither affected nor carriers, totally healthy and free.

7- Recurrent achromatopsia patients are married with healthy individuals who do not carry a defective copy of the same disease gene. In that circumstance, except for point mutations, the children are not at risk of being affected by the disease, but 100 percent are likely to be carriers.

8- In the hypothetical case of marriage with children of two people affected by the same type of recessive inheritance, the risk that the children inherit the disease of the genetic disorder would be 100% ......... if we re-read this point We could understand that the disorder is fixed in the Community when these marriages between direct relatives occur.

We must not fail to notice that this is only theoretical percentages. It should be added that these percentages will never be applicable to the total number of children, but to each child to be born regardless of what happened to his siblings. It is exactly like the coin to the air: each launch is a new case where the previous statistics are useless. You know that the chances of taking face or taking out cross are half and half, 50 percent for each. Whatever comes out is random regardless of how much it has been on previous occasions and how much it could come out in later releases.

Usually, in recessive disorders, symptoms begin in childhood or adolescence rather than at maturity (although for reasons not yet well understood, symptoms are not necessarily present at birth or infancy). However, this is no rule because in other disorders by recessive inheritance on several occasions there is also a late onset. This is what English speakers call "late onset" within this disorder.

The diagnosis of Acromatopsia is made by an ophthalmologist; Initially symptoms such as sensitivity to light or reduction of visual acuity may be important keys in the diagnosis. Examination of the retina may be normal. The color vision tests normally performed in the clinic are: the Ishihara test, the H-R-R test and the City University test. The diagnosis is confirmed by a special study called Electroretinography.

There is currently no cure for Acromatopsia. Studies in genetic therapies could contribute to the development of treatments in the future. Children should be evaluated for refractive errors (need for glasses). The prescription of glasses to correct refractive errors such as farsightedness, myopia and astigmatism can improve vision. However, the correction will not return the vision to its normal levels. Red lenses can help reduce sensitivity to light and thus improve the overall functioning of vision. Noir lenses can also help with sensitivity to light. Some examples are CPF 550 lenses (5% transmission darkening) and CPF 550XD lenses (4% transmission darkening). These lenses are available through Winchester optics (www.winoptical.com/medical/ecporder.htm). A new device called "eyeborg" can help people without color vision to perceive colors through sound waves. Artist Neil Harbisson who suffered from Acromatopsia was one of the first to use this device.

With proper help from teachers, children with Acromatopsia usually have the ability to go to normal schools. Sitting these children in the first row, increasing the size of the letters in the texts or the use of magnified devices can be very useful. A vision assessment is necessary, before the child starts school at school. Severely affected individuals may benefit from services available at the school specially designated for the visually impaired.

Currently the treatment is only experimental and goes on the side of Gene Therapy, which has been used in mice to restore damage in Human Acromatopsia; The researchers claim to have restored vision of mice with a mutation in the Gnat2 gene. It normally encodes a protein called alpha-transducin, which is essential for the survival and health of the photoreceptors of the cones. Mice are used as a model for studying human achromatopsia. The gene was injected under the mouse retina. Two months later, they examined the electrical activity of the retinas and found that most of the mice had responded positively to gene therapy. (W. Deng, J. J.J. Alexander, S. H. Min, Q. Li, J. Pang, J. Li, B. Chang, J. Lem, W.W.

Hauswirth, Dep. Of Ophthalmology, Univ. Of Florida Coll. Of Medicine, Box

100284 JHMHC, Gainesvill, FL. 32610-0284, USA, [email protected])

In extending the review of the literature, to my astonishment I found information about an Island called Pingelap in which there is a population with this genetic anomaly; So I was interested to know more about Pingelap ......

Pingelap is an atoll in the Pacific Ocean, part of Pohnpei, belonging to the Federated States of Micronesia, consisting of three islands: Pingelap Island, Sukoru and Daekae, attached to a reef system and surrounding a central lake, although only the island Pingelap is inhabited. The complete set has an extension of 1.8 km2 at high tide and less than 4 km2 at low tide. The atoll has its own language, the pingelapés, spoken by most of the 250 residents.

The atoll was captured by Japan in October of 1914, after the beginning of World War I. The southern part of Pingelap Island was occupied by Japan during hostilities in the Pacific Ocean in World War II, being used as a supply base and being attacked by Allied forces. The presence of foreign troops led to the introduction of infectious diseases, including gonorrhea, tuberculosis and dysentery, which reduced the population to its pre-war level between 1000 to 800 and significantly decreased the fertility rate.

Historically, the atoll was ruled by a supreme chief named nahnmariki; A hereditary title granting certain land rights to its owner. This system was maintained during the Japanese occupation, although it was renamed "magistrate of the island". However, with the arrival of the US Navy in 1945, a system of democratic choice was created and established along with the traditional system, whose power gradually weakened. Universal primary education was provided for island children and limited health care to eradicate diseases introduced during the war.

During the 1960s, the Peace Corps and the US Air Force Were established on the main island, building a missile observation station in the northeast of the island and a pier, starting construction of a landing strip in 1978, next to the lagoon, on the main island. The runway was completed in 1982, and currently fly between 2 and 3 daily aircraft to and from the atoll, operated by Caroline Island Air.

In 1775, typhoon Liengkieki swept the island, killing 90% of the population and leaving only 20 people. It is believed that one of the survivors, Nahnmwarki Mwanenised (the ruler of the time), was a carrier of complete Acromatopsia (known on the island as "maskun", literally "does not see" in pingelapés). This survivor. However, Acromatopsia did not appear until the fourth generation after the typhoon, being affected the 2.70% of the population. In the sixth generation, the incidence increased to approximately 4.92%. These statistics can be explained by inbreeding and by two related concepts, the bottleneck effect and genetic drift. In the case of Acromatopsia on Pingelap Island, the mutation fluctuated greatly from the third and fourth generation under an extreme form of genetic drift. This type of genetic drift occurs only when the population is extremely small (20 survivors after the typhoon) and is also known as the founding effect. Of course, cases of endogamy occur in both cases. To be able to recover the population of the atoll as fast as possible, survivors must perform a substantial amount of inbreeding in the first generations. Because relatives share many similar alleles inherited from their common ancestors, there is a high probability that offspring inherit the same allele from each parent. Since Acromatopsia is an autosomal recessive disorder, endogamy among the descendants of Nahnmwarki Mwanenised will result in an increase in the frequency of the recessive allele.

In addition, two crucial factors have made the gene pool of this place relatively small.

Studies carried out by the scientists during the years 2000, showed that the population of Pingelap, in addition to the Acromatopsia, in a great part had lack of visual acuity, photophobia and that 85% of them suffer a disorder that causes the pupils Open with very strong light and close in low light, ie the reverse of what happens normally

On one hand the remote location of the island. On the other, the local religion, which discourages marriage with foreigners. These conditions have helped the genetic mutation persist.

While suffering from this genetic defect on a radiant Pacific island has many drawbacks, it also has an advantage; As well as Sababantiari villagers are great night hunters, the people of Pingelap finally feel their element during the night, they go up to the boats to hunt flying fish. They hang lighted torches that attract fish like the night butterflies to light.

Today, the atoll remains a place of interest to geneticists because of the high presence of Acromatopsia; Because of the small gene pool and rapid population growth, the disorder is prevalent in at least 10% of the population, with 30% being carriers (compared to only 1 in 33,000 in the US, or 0.003%, are affected), leading the neurologist Oliver Sacks to write in 1997 his book "The island of the blind to color".

Oliver Wolf Sacks, was a Nurologist, Naturalist and British author, wrote books describing the neurological disorders of his patients; Some of these books were adapted to Movies; During his career he worked with a group of survivors of the lethargic encephalitis of sleep disease of the 1920s, who had been unable to move on their own for decades. Treatment of those patients became the basis of his book Awakenings (Awakenings). Due to the many books he wrote; The New York Times called him "the poet laureate of contemporary medicine" and "one of the great clinical writers of the twentieth century." His books include a wealth of narrative detail about his experiences with patients, and how to deal with their conditions, often illuminating how the normal brain deals with perception, memory and individuality. Awakenings (1973) was adapted into an Academy Award nominated film in 1990, starring Robin Williams and Robert De Niro. He and his book Musicophilia: Tales of Music and Brain were the theme of "Musical Minds," an episode of the PBS Nova series.

I have read the Book of Oliver Sacks and certainly must have felt exactly the same as I did upon learning of the existence of a distant population where a good number of people suffered from this hereditary defect .... Medical interest, exaltation, concern; It is not very easy for physicians to stay without doing anything about it when we hear something like this; But Oliver Sacks mentions in his book about other similar findings and that it increases even more the expectation; I suggest you check out the following link: Https://www.youtube.com/watch?v=CM06G26X-rQ, he will see in different videos the summary of Oliver Sacks' visit to Pingelap and the surprising findings that led him to write the precious book "The Island of The blind to color "

For example, Sacks, in his book, mentions the fiction novel written by HG Wells "The Country of the Blind" in which describes a people discovered by chance by a Monta?ero surnamed Nú?ez in the Ecuadorian Andes to slip and fall for a Snowy hillside When he gets up, he realizes that he is stunned in a valley isolated from the rest of the world by deep cliffs, the Country of the Blind. The ancestors of their inhabitants fled from Spanish repression from Peru and a strange disease spread among them, causing all their descendants to be born blind. Published in 1904 in The Strand Magazine, this account is one of the most brilliant texts on blindness as a metaphor. It addresses topics such as human knowledge and society, and shows how the community subjects the different to their beliefs, eliminating it for being different.

Here a brief but extraordinary paragraph of this brilliant novel: "And Nunez found himself trying to explain the wide world from which he had fallen, the sky and the mountains, the vision and other prodigies like those ... And they refused to Believing or understanding nothing of what he said to them ... They did not even understand many of his words.For fourteen generations, those people had been blind and isolated from the world of the seers.the names of things alluding to the vision had been forgotten and had changed."

Also in the same Book of Oliver Sacks we find information about other books that comment on hereditary defects like the book of Nora Ellen Groce who comments on multiple cases of Deafness in the Island of Martha's Vineyard in which a boat Captain and his Brother apparently from the city of Kent settled there in 1690; Both normally heard but were carriers of a recessive deaf gene. Over time, thanks to the isolation of the island and to the marriages between members of that closed community, the gene was inherited by the majority of its descendants. By the middle of the nineteenth century, in the towns of the North of the Island, a quarter or more of the population had been born totally deaf.

This story at the end, because it is a closed community that inherits a recessive defect seems similar to our truth ??? .... and so perhaps how many more communities could there be in other latitudes?

So.....this history maybe to be continue.....I have many information about this one and another genetics disorders in close communities of my country......