The Sandhoff Disorder within  the Maronite Cypriot Community 

By Guita G. Hourani
Chairwoman of MARI

At the invitation of Dr. Imad Aboujouade and Dr. Elias Touma, Dr. Anthi Drousiotou participated in a medical conference organized by The Center for Reproductive Medicine and Genetics at Aboujouade Hospital in Jal-el-Dib, Lebanon. In her lecture, Dr. Drousiotou shared the results of her research on the Sandhoff Disorder that was recently identified within the Maronite Cypriot community.  MARI's staff attended the lecture and met with Dr. Drousiotou who explained that the Sandhoff disorder is not a communicable or contagious disease.

Photo of Dr. Anthi Drousiotou presenting her paper.
Photo by MARI, (Lebanon, 1998)

According to Dr. Drousiotou, who is a Senior Biochemist at the Cyprus Institute of Neurology and Genetics in Nicosia, Cyprus, the Sandhoff disorder "is an inherited neurological disorder named after the German scientist who first described it. It is caused by a defect on the genetic material (DNA) which results in a deficiency of the enzyme hexosaminidase. This enzyme is responsible for the breakdown of a fatty substance abundant in the brain and nervous system known as ganglioside GM2. In the Sandhoff disorder, this and related substances cannot be properly metabolized and accumulate in the nervous tissue as well as in other organs like the liver, the spleen and the kidneys." 

"Genetic disorders are found in all populations." Dr. Drousiotou explained. "Every one of us carries 5-7 disease-causing mutations (mistakes in 5-7 of the 3 billion letters of the genetic code). This is no problem unless we marry somebody who happens to have the same mutation(s). The chance of this happening is usually extremely small unless certain conditions prevail, for example inbreeding or when the carriers of a particular mutation have a biological advantage over the rest of the population. Different populations have different genetic disorders.  For example the Greek Cypriots have the highest frequency of thalassaemia carriers in the world, 1 in 7." 

When asked about the reason why she is concerned with the Maronite Cypriot community, Dr. Drousiotou replied, "during the last fifteen years three Maronite children in Cyprus, belonging to three different families, were diagnosed as suffering from Sandhoff disorder. This number is greater than the expected number based on the incidence of the disorder found elsewhere and taking into account the size of the population and the birth rate. " 

Dr. Drousiotou stated that when these children were born "they looked absolutely normal. The first clinical symptoms became apparent after the 6th month of life and these included unresponsiveness to the environment, a startled reaction to noise and megalocephaly (enlarged head). The children went on to develop psychomotor retardation, seizures, blindness, deafness and spasticity. After the 2nd year of life they were in a vegetative state and suffered from frequent infections." She went on to declare that "in the absence of a treatment for Sandhoff's disorder, all children died before the age of four." 

When asked about how a child could be affected with the Sandhoff disorder, she replied that "for a child to be born with Sandhoff he/she must inherit two defective copies of the gene, one from each parent who are carriers of the disorder. The risk of two carriers having an affected child is twenty-five percent." 

As for the incidence of the Sandhoff disorder in the USA and other communities around the world, Dr. Drousiotou said, "in the USA the incidence of the disorder has been estimated to be about one affected child per 360,000 births resulting from a carrier frequency of about 1 in 300. Increased frequency of Sandhoff's disorder has been reported in some geographically or demographically isolated communities for instance: In the Cordoba province of Argentina, the carrier frequency was estimated to be about 1 in 26. There were also reports of an increased number of Sandhoff patients in a small community of Metis Indians in Canada." 

Dr. Drousiotou and colleagues organized visits to the Maronite cultural centers where they first disseminated information about the disorder. Then a blood collection from Maronite Cypriots, Lebanese and Greek Orthodox was arranged. The total number examined was 415 persons. Dr. Drousiotou explained how the researchers determined the carrier status. She illustrated that this "was done by measuring the enzyme hexosaminidase in the blood. Carriers of Sandhoff's disorder are completely asymptomatic and have low levels of the enzyme but not as low as found in patients." 

The results of the research carried out by Dr. Drousiotou and her team show a high frequency of Sandhoff carriers among the Cypriot Maronites, approximately 1 in 8. Dr. Drousiotou suggested that the disorder is probably evident in the Maronite community in Cyprus because "over the centuries the Cypriot Maronites have tried hard to maintain their ethnic and religious identity and as a rule they married within the community. Therefore, the high frequency of Sandhoff carriers in the Maronite community of Cyprus seems to be the result of a founder effect followed by inbreeding." She added, "it is not clear at this point whether the Sandhoff disorder was brought to Cyprus by one of the original Lebanese immigrants or whether it arose in Cyprus at a later stage. Sandhoff's disorder has been found both among Lebanese in Canada and in Lebanon in five different ethnic/religious groups." 

When asked about whether the community in Cyprus has been informed, Dr. Drousiotou stated that "the Maronite community in Cyprus has been alerted about the problem and people come voluntarily to be tested before marriage or before having children. If both partners in a couple are found to be carriers, they are given genetic advice. The risk of two carriers having an affected child is twenty-five percent." 

The Sandhoff disorder is like any other syndrome which is not exclusive to one community or another. People should not be so inhibited as to refuse to seek testing for the disorder or even follow any medical advice. Those who are not concerned with this disorder should not form an idea that all the Maronites are carriers of this disorder whether in Cyprus or elsewhere. Any discrimination based on this information is certainly condemned by Dr. Drousiotou and the Cyprus Institute of Neurology and Genetics.

A lot is known about the biochemistry and pathophysiology of this disorder but what is not known is how to cure it. This brief is published to increase knowledge of the disorder with the hope that a cure will be found.   Meanwhile, not every Maronite should be tested.  this will cause unnecessary worry and expense. Since there is no evidence at the moment that Sandhoff frequency is increased in other Maronite communities, screening should be limited to Cypriot Maronites and persons coming from families where Sandhoff exists, i.e. where children with Sandhoff were diagnosed or died of it in the past. The screening test is available at good genetic centers all over the world. 

The results of Dr. Drousiotou's research will soon be published in medical journals. Should anyone be interested in more details, please contact Dr. Drousiotou at the following address: 

Dr. Anthi Drousiotou
Senior Biochemist 
Department of Biochemical Genetics
The Cyprus Institute of Neurology and Genetics
P. O. Box 3562 1683 Nicosia, Cyprus

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