Introduction
Tay-sachs disease is a metabolic genetic disorder that is transmitted through autosomal recessive heredity. The cause of this disease is a defect in the activity of hexosaminidase (A) and glycolipid accumulation in cell lysosomes [1]. Beta-hexosaminidase has two types of isoenzymes called beta-hexosaminidase A and beta-hexosaminidase B.
The beta-hexosamine-amidase A is coded by the HEXA (24-15q23) gene and the beta-hexosamine-amidase B is coded by the HEXB gene [2]. The mutation in the hexosaminidase A gene results in a deficiency of the activity and deficiency of the beta-hexosamine-amidase A enzyme and Tay-sachs disease [1, 2]. In contrast, the mutation in the hexosaminidase B gene results in deficiencies and deficiencies in the enzyme beta-hexosamine-amidase A and B, and thereafter, results in a similar disease commonly known as Sandhoff disease [2].
Tay sachs disease is rare and has been reported one in about 2000 in the Western countries. In some populations, such as the Ashkenazi Jews of Eastern Europe and the French Canadians in the Quebec area, the disease is ten times more common [2-5]. In the classic infant form, the symptoms usually begin at the age of 6 months and progress quickly, and at the age of 3 to 5, they cause the death of the patient [6]. Usually, infants with this condition normally grow naturally in 3 to 6 months and then develop a nerve regeneration, gradually lose their skills, develop irritability, general weakness and seizure, decrease consciousness, hearing and vision, and they end up in spasticity and die [1, 3]. In almost all patients, cherry red spot is seen in the eyes. Due to the accumulation of sphincolipid in the brain and neurons, in advanced stages of the disease, in the white matter of the brain, demyelinization occurs in the neuronal cells, swelling and ballooning. These symptoms can be detected in brain biopsy or autopsy samples. In the non-invasive imaging of the brain in the early stages of the disease, a resonant signal is seen in the basal ganglia, potamene, thalamus, blubber nucleus and white matter of the brain in radiological images. In the more advanced stages of the disease, the gray part of the cerebral cortex is degenerative and atrophic [7-9].
Diagnosis of Tay-sachs disease is performed by measuring the activity of the hexosaminidase A enzyme in the white blood cell and skin fibroblasts, or, in another way, diagnosis is obtained from the molecular analysis of the hexosaminidase A gene in the DNA extracted from the cells. In the past, tests such as rectal biopsy and sphonglipid observation have been used in ganglion cells of the intestinal wall, which are now obsolete [10].
In this article, six cases of infantile classic infected cases confirmed by measuring enzyme activity were reported.
 
Patients and methods
First case: This case was a healthy year-old boy, the only child of a family with parents with third degree kinship who was born as the result of normal pregnancy and delivery through cesarean section. The birth weight of the neonate was 2830 grams, 49 cm high and 34 cm wide. The same illness was not mentioned in other relatives. the child development was almost normal until the 5-4 months, and then it was delayed in development. The patient's apparent symptoms included a delay in growth and development, lack of attention to others, irritability, and evolutionary regression. There was a cherry red spot in the patient's eye examination. A level of acid phosphatase was reported in the patient's blood. In the disorder in the myelin section, it was a sign of desmilinisation. Bone marrow test was not performed for the patient. With regard to course of disease, history, apparent phenotype of the patient and other symptoms, the diseases of the sphygulopidosis group including the coronary arteries, Gaucher`s disease, Niemann-Pick disease,Tay-sachs disease and Sandhoff disease were diagnosed in differential diagnosis. The blood sample and biopsy of the skin were sent to one of the metabolic centers in the Netherlands and the results indicate a defect in the enzyme beta-hexosamine amidase A and diagnosis of Tay-sachs disease.
Second case: This case was a 2-year-old girl, the only child of the family with the parents with grade 3 kinship. She was healthy and a result of normal pregnancy and delivery. The child's uncle died at the age of 3 with similar symptoms. The birth weight of the baby was 3000 grams and the head circumference was 34 centimeters. The development of child up to 6 months of age was almost normal, so that at 6 months of age he knew parents and looked around. After that, she was delayed in evolution and growth. The patient's apparent symptoms included growth retardation, lack of attention to others, irritability, mental retardation, seizure, kyphosis, developmental regression, and nystagmus.
During the examination, she was drawn to a violent face with hirsutismt. Her visual and auditory power decreased, and her liver was somewhat large, that liver biopsy showed generalized stasis. Screening of metabolic, normal and high levels of acid phosphatase was high. A normal bone marrow test was reported, and there was a double-sided chery red spot in the patient's eye examination. In the disorder in the myelin section, it was a sign of desmilinisation. According to the course, history and apparent phenotype, blood samples and skin biopsy of the patient were sent to one of the metabolic centers in the Netherlands and the results indicated a deficiency of the enzyme beta-hexosamine amid A and Tay-sachs disease diagnosis was confirmed.
Third case: This case was A 14-month-old girl, the only child of the family whose parents had grade 3 kinship, healthy, and she was result of a normal pregnancy and delivery. The baby's weight at birth was 3340 g. The same illness was not mentioned in other relatives. The development of infant was almost normal up to 4 months, and then has been delayed in growth and development. Symptoms of the patient included delayed growth and development, lack of attention to people around her, irritability, mental retardation, evolutionary regression, hypotension without organomegaly. There was a douple-sided cherry red spot in the patient's eye examination. In this disorder, in the myelin section, was a sign of desmilinisation. Bone marrow test was not performed for the patient. The blood sample and biopsy of the skin were sent to one of the metabolic centers in the Netherlands and the results indicate a defect in the enzyme beta-hexosamine amidase A, and the diagnosis of Tay-sachs was confirmed.
Fourth Case: This case was a 7-year-old girl, the only daughter of a family with parents who had kinship with eachother. She was healthy and was a result of a normal pregnancy and delivery. The same illness was not mentioned in other relatives. The child's development was almost normal until the age of 4, and after that, she suffered from a delay in growth and development. The patient's symptoms included developmental delay, imbalance, irritability, mental retardation, kyphosis and evolutionary regression. There was a cherry red spot in the patient's eye examination. In this disorder, in the myelin section, was a sign of desmilinisation. Bone marrow test was not performed for the patient. The blood sample and biopsy of the skin were sent to one of the metabolic centers in the Netherlands and the results indicate a defect in the enzyme beta-hexosamine amidase A, and the diagnosis of Tay-sacks was confirmed.
Fifth case: This case was a5-year-old girl, the only daughter of a parents who had kinship relationship.
She was healthy and was pregnant and had normal delivery. The birth weight of the baby was 2800 gr and height was 49 cm. The same illness was not mentioned in other relatives. The childhood growth was almost normal before the 19th month, and then she was delayed in development. The patient's symptoms included imbalance, muscle weakness and seizure, developmental delay, irritability, mental retardation, evolutionary and non-organomegaly regression. There was a cherry red spot in the patient's eye. The level of acid phosphatase in the patient's blood was high. Bone marrow test was not performed for the patient. The blood sample and biopsy of the skin were sent to one of the metabolic centers in Germany, and the results indicated a deficiency in the enzyme beta-hexosamine amidase A. Accordingly, a molecular study was performed and Tay-sachs diagnosis was confirmed.
Sixth case: This case was A 23-month-old boy, the only son of a family with parents with grade 3 kinship. He was healthy, and the product of normal pregnancy and delivery. The birth weight of the baby was 2850 grams. The same illness was not mentioned in other relatives. The baby's growth was almost normal before the age of 7 months, and then hewas delayed in growth and development. The patient's apparent symptoms included growth retardation, lack of attention to people around him, irritability, mental retardation, hypotonia, and evolutionary regression. There was a double-sided cherry red spot in the patient's eye examination. In this disorder, in the myelin section, was a sign of desmilinisation. Bone marrow test was not performed for the patient. The blood sample and biopsy of the skin were sent to one of the metabolic centers in the Netherlands and the results indicate a defect in the enzyme beta-hexosamine amidase A, and the diagnosis of Tay-sachs was confirmed.
 
Discussion
Tay-sachs disease is a neurodegenerative disease of lysosomal stores, which occurs due to the accumulation of sphingolipid in visceral cells and neurons. The disease is inherited through autosomal recessive inheritance [1-3]. This disease appears in three clinical forms:
1- Classical and acute infant type
2. An sub-acute juvenile type, whose symptoms are delayed, and the course of the disease is slower.
3- Adult and chronic type, which begins with signs of adolescence and puberty, and progresses slowly.
In the first type, symptoms begin at about 6 months of age and progress quickly and cause deaths at the age of 3 to 5 years. The outbreak in western societies is one in 200,000 and is even more prevalent in some societies. It seems that in Iran, due to the abundance of family marriage, metabolic diseases such as Tay-sachs are relatively common. It is noteworthy that in this study, the parents of all six patients were relatives. This illness was first described by the Warren-Tye in 1881, with "eye" demonstrations [3].
The subunit defect of the hexosamineminide A gene is in the long arm of chromosome 15 [1]. Tay-sachs disease is detected by measuring the amount of enzyme in the serum or white blood cells. More than 100 mutations have been confirmed in hexosaminamide A gene, some of which are linked to specific racial groups. The beta-hexosamine-amidase enzyme A has two isoenzymes, beta-hexosaminodiosis A and beta-hexosaminodiosis B. The beta-hexosaminetidase enzyme A has two alpha and beta subunits. The hexosaminidinose B gene is located on the long arm of chromosome 5 [4]. The mutation in hexose aminidose A subunit causes the decrease in beta-hexosamine-amidase A and, as a result, causes Tay-sachs disease. The mutation in hexosaminamidase B beta subunit reduces both beta-hexosaminidase enzymes A and B and causes Sandhoff disease.
In the eye examination of the patients, the optic nerve is normal, but in the retropharyngeal region, a circular, dyed, white area is observed with a distinct edge. In the middle of this area, there is a circular, brownish brown spot. This sign has also been reported in other illnesses such as Gaucher disease, Sandhoff disease, Gangliosidosis type 3, Niemann Pick disease, Sialidosis, Farber, Type 3 muculipidosis, metachromatic leukodystrophy, Multiplex sulfatase deficiency and Wolman disease [11]. The reason for appearance of a dyed region in the back of the eye is the presence of multiple layers of retinal ganglion cells in this area. Lipids, sphincolipids or oligosaccharides accumulate in the cellular layers of this area in an abnormal amount. In the middle of this dyed region, there is a dent that does not have ganglion cells and retains its red color. The red color is due to the presence of a pigmented epithelium and a choroid retina. In each of the 6 patients, a cherish red spot was observed in the examination of eyes.
 
Conclusion
Clinical, imaging and enzymatic findings were collected in all 6 Tay-sachs patients. Although this disease is rare,  because of the abundance of kinship marriages in Iran, with the observation of signs of neuroregressive malformation in a child who have normal growth in the first few months, we should be aware of sphincopleposis, including Tay-sachs disease. Due to autosomal recessive inheritance, the risk of repeatation in subsequent pregnancies is 25%. Therefore, in order to prevent the recurrence of the disease, a definitive diagnosis is necessary by measuring the activity of the enzyme beta-hexosamine amid A in a molecular and genetic way and checking mutations in the hexosaminidase gene. In this case, with pre-birth diagnosis, the infected embryos can be detected and, with the consent of the parents, their birth can be prevented.