Congenital Minamata Disease

History

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Minamata Bay, Japan
     Minamata Disease is due to organic mercury (methylmercury) poisoning and although not very common in the US, Minamata Disease was first discovered in Minamata City, Kumamato Prefecture, Japan. The Chisso Company, which synthesized acetylaldehyde and used mercury compounds as catalysts, had dumped over 27 tons of mercury compounds over a 30 year time period into Minamata Bay. The Bay provided fish to thousands of residents who not only consumed them, but also sold the fish for business. Between 1953 and 1956, 54 victims were initially observed. Soon after, a study group in Kumamoto University School of Medicine in Japan found that the disease and symptoms they were observing among residents could be attributed to methylmercury poisoning. In Minamata Bay, this was due to the consumption of seafood from the poisoned Bay (Eto, et.al., 2010). Initially, Chisso Co. refused to assume responsibility for the disease and the government refused to take any action. Only after scientists and doctors proved that Chisso was releasing a mercury product into the Bay and that the Minamata Disease patients all displayed signs of mercury poisoning did the company and government assume responsibility for the pollution with compensation (Kondo, 2000). However, even though over several decades the Bay was cleaned for mercury, by then many had already suffered and the damage done to its residents was irreversible.

      Minamata disease was present both in adults and infants, with an array of phenotypes. It was described that children born between 1955 and later whose mothers ingested the fish or shellfish from Minamata Bay displayed severe neurological deficits even if the mothers themselves did not display those symptoms (Castoldi, et.al., 2001). Initially, the early signs for congenital Minamata poisoning were mistaken for other pediatric diseases like cerebral palsy. 
      Sadly, a decade after this disaster in Minamata Bay another incident in Iraq occurred with methylmercury poisoning. This time, the poisoning occurred not through the mother’s ingestion of fish, but ingestion of contaminated bread from grain; the seed of this grain was treated with a methylmercury fungicide. Analysis of this incident was done by showing that maternal-hair levels of methylmercury were significantly higher in women exposed to methylmercury and later their child’s neurological development was altered due to certain levels (Marsh, et.al., 1987). 
     Both incidences lead to studies that showed that the nervous system was very vulnerable during early development to methylmercury and the signs of poisoning were manifested in the child by delayed developmental milestones, such as language and motor function (Grandjean, et.al., 2011).

Symptoms and Molecular Findings

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A crippled person with Minamata Disease (From Aileen Archive)
          The symptoms of fetal methylmercury intoxication are different when compared to adult symptoms. Indications of this disease take some time to become apparent in infants and children. Congenital Minamata disease in an infant displays cerebral-palsy-like symptoms such as mental retardation, primitive reflexes, ataxia, dysarthria, and deformity of posture. Some even suffer repeated convulsions and salivate copiously (Grandjean, et.al., 2011). After autopsies of fetal cases, it was observed that there was significant loss of neurons and hypoplasia (poor neurite and neuron development), and inappropriately positioned and located neurons in the cerebral cortex. These findings were believed to be a result of ingested methylmercury and its absorption through the mother's placenta and selective accumulation in the brain. Further molecular studies indicate that methylmercury has an affinity for thiol groups so proteins with cysteines may easily be modified by methylmercury (Chang, et.al., 1998). For example, microtubule function is compromised due to the presence of methylmercury since  its function is so crucial to normal development of the nervous system for cell proliferation (Choi, et.al., 1978).

      There are no known cures for Minamata disease and only prevention serves as the main way to avoid symptoms and exposure. After the Iraq incident, much research was done to establish the exposure limits for pregnant women and international guidelines were based on three very important cohort studies. As shown in Table 1, in 2003 the international exposure limit was established as 1.6 microgram/kg per day or in other words pregnant women are advised not to eat more than 12 ounces of low mercury fish per week (Grandjean and Herz, 2011). Today, you can see warning signs at grocery stores even in the frozen food isle indicating the dangerous neurotoxic effects of methylmercury and the consumption of seafood products.

      Several cases of environmental methylmercury intoxication occurred since the incident in Minamata Bay. These incidences have impacted not only medical research on mercury intoxication, but they have also had a broad impact socially and economically. In the case of Minamata Bay, fisherman were out of work because no one would buy the fish caught from the Bay. There was even a stigma for those affected, and due to the ensuing deformities from intoxication, people could not work. Children were born that needed more medical care and attention, thus limiting resources further for families with members suffering from Minamata Disease. Although there are no monetary estimates for families that deal with Congenital Minamata Disease, a close estimate is that of families with children that suffer from cerebral palsy due to its similar symptoms. The estimated average lifetime cost is about one million dollars on health care and other costs for families that deal with cerebral palsy (National Institute of Neurological Disorders and Strokes NINDS). So although there is no cure, one can seek treatment through physical therapy and etc. Unfortunately, developing new neurons is not scientifically feasible as of yet, so treatment and prevention remain the main ways to work with Congenital Minamata Disease.

      Methylmercury pollution has huge implications on the environment and for everyone who is poisoned from consumption of seafood from the effected areas. In addition, there are other ways develop mercury poisoning as well. Worldwide, it has so far affected thousands of infants who were born with the disease. Specifically for the case of Congenital Minamata Disease, pregnant mothers are most at risk for giving birth to infants with this disease due to the molecular effects of methylmercury. Prevention of poisoning and environmental codes prohibiting pollution will be imperative to prevent any further catastrophes from occurring. 


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Introduction and background section completed by Ashiya Hamirani

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