February 28, 2014

Rare Disease Day

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On the occasion of Rare Disease Day 2014:
The Centre for Arab Genomic Studies issued a report about rare diseases in Arabs

As many countries around the world will be organizing special activities to mark the Rare Disease Day which happens to be on Friday 28th February this year, the Centre for Arab Genomic Studies (CAGS) issued a special report about rare diseases in Arabs. CAGS, a division of Sheikh Hamdan bin Rashid Award for Medical Sciences, strives through the abovementioned report to provide a clear picture about prevalence rates of these conditions locally and regionally. This information is a prerequisite to formulating strategies pertaining to diagnostics, therapeutics and prevention in the context of rare diseases, bearing in mind that general interest among Arab countries in these conditions lags behind their more common counterparts.

Dr Mahmoud Taleb Al Ali, Director of CAGS, explained how this report represents one of the many activities undertaken by the Centre in order to characterize genetic disorders among Arab populations. This extensive work relies on high quality data that has been published in internationally peer-reviewed journals. All this data make together the perfect input for the Centre’s database (CTGA), which is regularly updated with the latest information in the field of human genetics.

The report mentioned that despite the high number of currently known rare disorders (7000 – 8000), when lumping these conditions together one finds that they are anything but rare. In fact there are hundreds of millions of people who suffer from rare diseases around the world. Notably there are many of these conditions that await proper clinical and molecular identification. Moreover, uncovering underlying causative mechanisms of each one of these disorders is a considerable challenge to the medical milieu because of the level of clinical complexity therein.

The Catalogue for Transmission Genetics in Arabs (CTGA) database lists 443 rare diseases among Arab populations. This is significantly higher than the figures reported by CAGS in 2012c, which reflects the rapid quantitative and qualitative increase in the content of CTGA over the past few years. All this has made the CTGA the largest ethnic-based database worldwide and bring it to become a major referential source of information about rare genetic disorders in Arab populations.

The report mentions that the majority of rare disorders are either genetic by origin or have a significant genetic component (with recessive or dominant mode of inheritance). On the other hand, few disorders are caused by erroneous immune reactions or from exposure to certain infectious agents.

Prevalence rates for rare diseases differ widely; some are extremely rare conditions with only few diagnosed patients worldwide while others are much more common. An example of the former type of conditions is Hutchinson-Gilford Progeria Syndrome with only one locally documented case from Abu Dhabi – UAE (as mentioned in the CTGA entry for this condition). This condition is lethal and affected children develop signs and symptoms of premature aging such as wrinkled skin, growth failures and cardiovascular disease. Additionally, prevalence rates vary from one geographical region to another, with some of these disease having higher prevalence rates in Arab countries than the rest of the world. One notable example is Xeroderma Pigmentosum which involves photosensitivity, early aging of the skin and a high incidence of skin malignancy. This disorder has an entry in CTGA and it reports studies from UAE, Qatar, Tunisia, Palestine and Egypt.

The term Rare Diseases encompasses a wide range of heterogeneous disorders that differ from each other in a number of characteristics, including prevalence, clinical progression and etiology. The CTGA displays clearly the category of each of the rare diseases within it, so it contains two major groups of these conditions; Inborn Errors of Metabolism (IEM) and diseases caused by defects in DNA repair mechanisms. Inborn Errors of Metabolism cover a number of rare diseases such as Biotinidase deficiency which results from the inability of the body to utilize the vitamin Biotin. Biotin is necessary for normal metabolism in humans as it plays an important role in the metabolism of fats and amino acids, aerobic respiration, and cell growth. This deficiency results from a mutation in the Biotinidase gene (BTD), in which a number of novel mutations were reported in the Emirati population. The latter data came from a comprehensive study that was conducted at Tawam Hospital in collaboration with Sultan Qaboos University.

Various degrees of deficiency affecting the enzyme phenylalanine hydroxylase result in Phenylketonuria (PKU). Phenylalanine hydroxylase mediates the conversion of phenylalanine into tyrosine, which is necessary for the production of certain hormones, neurotransmitters, and melanin. If left without management, this disorder leads to the buildup of phenylalanine in the body with major developmental consequences. The latter include mental retardation, hypopigmentation, and psychological problems. A comprehensive survey for birth prevalence of PKU in the UAE between the years 1994 and 2000 yielded the rate of approximately 5/100,000 [5]. Numerous mutations were reported to cause PKU, some of which seem to be unique to the UAE.

A number of rare diseases fall under the category of defective DNA repair disorders. These are characterized by having ineffective protection from DNA changes due to constant exposure of the human genome to various sources of damage. Fanconi anemia is a good example of this subgroup of rare diseases; it is a recessive condition which can lead to bone marrow failure (aplastic anemia), leukemia, and solid tumors. Many of those affected suffer congenital defects of the skin, arms, head, eyes, and kidneys, as well as developmental disabilities. Upon screening 24,233 consecutive live and stillbirths in Abu Dhabi, UAE, one case of Fanconi anemia was observed in a consanguineous family. This incidence rate may reflect higher UAE incidence compared to the international figure (1/350000 births).

Raising collective awareness about rare diseases among affected and non-affected families was the most important feature of this year’s activities pertaining to Rare Disease Day. The latter activities took place under the patronage of Sheikh Hamdan Award for Medical Sciences.

On Friday 28th of Feb the Award is holding a number of activities at Zayed bin Mohammed Family Gathering in the presence of patients and their families as well as other members of the public. This gathering aims at bolstering the role of premarital genetic counseling as a way to rid our societies from misconceptions and common myths in this regard.