Ataxia-Telangiectasia (A-T) is an inherited multisystem disease that transmitted as recessive autasomal and appears with telangiectasia in skin & eyes of a patient, acute cerebellar ataxia, degrees of immune shortage, being prone to affection to pulmonary infections and lymph reticular malignant and brain tumors.
The neuralgic symptoms form usually clinical image of disease that appears during a child's walk learning. This disease causes acute disability so that a patient is always dependant on others for nutrition and care.
In this report, one case of this disease is introduced from section of Imam Reza’s (peace upon him) Hospital that in addition to complete nervous, dermal, ocular, infectious symptoms with acute Lymphoblast Leukemia.
Key Words: Ataxia, Telangectasia, acute Lymphoblast Leukemia, repeated infections.
Ataxia-Telangectasia is an inherited disease that is the most prevalent reason of children's chronic ataxia and has been reported for the first time in 1941 and also known with other names including Louis-Bar Syndrome.
Gene of disease locates on liq 22.3-q23.1 chromosome and is transmitted as recessives autasomal. Its incidence has been reported 1-2%. From important feature of this disease that has diagnosis aspect is dermal symptoms as venous extension (telangiectasia). Ataxia appears at the beginning of nervous symptoms that finally causes to patient’s disability. Other main signs are disorder in eyes moves as ocular agrarian, immune disorder that causes to repeated infections and finally chance of 50-100times for affection to lymph reticular tumors (leukemia and lymphoma) and brain tumors.
In this report, one case of this disease is reported with total nervous, eye, infectious and dermal symptoms with affection to acute Lymphoblastic leukemia from pediatric section of Imam Reza’s Hospital (peace upon him).
A patient is a 13 years old boy from Radkan (Birjand’s sections) who has been hospitalized in pediatric section of Imam Reza’s Hospital because of fadedness and inflammation of limbs. His parents reported onset of disease from about one month before hospitalization as high fever, cold signs resistant to therapy, fadedness and progressive weakness so that a patient was well until 4-5 years old and down respiratory diseases. He always had high fever and his parents noticed at changing of motive position of patient gradually so that involved in tremor of limbs and disability in walking. These changes are so procreative that has caused his disability after two years.
One year after beginning above signs, eyes unusual moves has started as unusual and uncontrollable leap jerking and after a short time, vascular damages have occurred at first on eyes then on nose and chins and other parts of body. His parent is sixth child of family and also his smaller sister is affected to this disease now (picture 2) and one child has died in age of 7-8 months old because of repeated respiratory infections.
In relative history, 5 children of his older uncle died in ages of 7-8 months old because of repeated respiratory infections, and two children died in 14-18 years old with similar leukemia and by affection to blood cancer. Another uncle of him, who married with his cousin, has 4 children now. Two of them are affected to this disease now. His aunt who married with her cousin (her father's brother's son) has two children. They died in6 and 8 months old because of respiratory infections.
The patient is a13 years old boy who is completely disable and is mental retarded. Leaping moves are seen in organs as ataxia. His skin has state like scleroderma (decreasing of elasticity) and telangectasia is obvious on nose skin, auricle and upper part of body. Cervical lymph nodes are touched larger than usual. In examination of lungs, wet & scattered rails are heard without wheezing from both of lungs. Sound of heart is normal, liver spleen is touched about 3 cm under edge of vibe. In organs, in addition to high leanness, obvious transformation of under organs with ataxia and leaping moves in them are seen and reflexes tendons have been intensified (figure 1, 2). Done tests are as follows: CBC = 31200 + 1% necrophilia and 75% BLAST, RBC = 2000000, number of platelet =1000 mβ, hemoglobin = 6.2gr per 100, MCV =110 femtoliter, MCH = 24 Pico grams, MCHC = 23.4, CRP = 2+, total test of urine=negative, IGA =130(70-312 normal), IgG = 640 (639-1349 normal), IgM= 85 (56-352 normal), CEA =3.1, alpha-fetoprotein = 340(30 nano gram/ml normal).
In chest XR diffuse infiltration and bone density decreasing, and in brain CT scan cerebellum density decreasing, were observed. Regarding findings, the patient’s done under aspiration of marrow in the case of leukemia and with observing more lymphoblast, diagnosis of leukemia was confirmed from type of ALL (L2) and he was located under suitable chemotherapy.
Also suitable wide antibiotics were used for him for therapy of pulmonary sinus infections, but because of weakness and server cache tic and appearance of danger signs, he died after several days.
Ataxia telangiectasia (A-T) is a series of disorders of different systems of body that is accompanied by various symptoms such as eye and dermal telangiectasia, neoplasm, disorder in action of immune system and repeated pulmonary sinus infections and Endocrine disorders. The most prevalent reason of ataxia is accompanied by nervous degeneration. Ataxia is usually the first nervous sign of these patients that appears gradually about 2 years old and improved so that causes disability in moving during maturity. This complication is appeared because of gene mutation that is called ATM (AT, mutated) and recognized by positional cloning. Obtained mutation causes decrease of a protein that is necessary for protection of damage of DNA. The function of ATM in function of core determines being prone of these patients to cancer and immune loss too but doesn’t determine nervous degeneration of these patients that is usually the first clinical signs of disease and causes progressive disability. Some other researchers said that the reason of increase of being prone to repeated infections and cancer in these patients is non balance in production of sensitive types to Oxygen (React Oxygen Species) in T calls of them so that in dons considerations, amounts of antioxidants like retinol & Alpha tocopherol, and also the capacity of antioxidants in patients of A-T, they are more sensitive to ionizing ray so that disorder of chromosome existed in this disease increases danger of creating neoplasm after exposure to ionizing ray. It has been said that exposure to ionizing ray causes naturally to activation of nucleus factor (NF Kappa B) but this answer is wrong in cells that are prepared from patients affected to ataxia telangiectasia. Cells that are prepared from patients affected to this disease have need to the obvious deficiency in two ends of chromosome in the form of end to end associations. This chromosomal disorder increases the incidence of degeneration of nervous cells specifically the purkinje's cells of cerebellum in these patients too. Ataxia telangiectasia are the nervous complications that are accompanied with shortage of immunoglobulin of A, E in the forms of superlatively or collectively (in 50-70% of patients) and degrees of shortage of cells of B, T. Mr. Mack Donald has reported an unusual case of dig monoclonal gammopathy of IgA type of kappa from one 2 years old girl affected to this disease so that analysis of low immunoglobulin of this disease has reported the high increase of part of IgA with amount of 672mlg/dl (normal 14-123mlg/dl) but IgM & IgG have been normal.
In more than 50% of cases, the amount of immunoglobulin of IgE, IgG4, IgG2, and IgA is low and pulmonary sinus infections are seen with a reason of decrease of activity of immune system. The disease of ataxia telangiectasia is almost accompanied with immune decrease especially immune globalizes of IgA so that it was said the existence of immune shortage and chromosomal fragility are obvious signs of Nijmegen. It was reported the amount of IgA=130mg/dl, IgG =640mlg/dl in our patient that both of them are normal. Mack Donald reported one 2 years old girl affected to this disease in 1999 as the first case that amount of IgA in that is very high (672mlg/dl, normal: 14-123). On November of 1999, Seddighi reported the existence of hyper gamma globulinemia & oligomonoclonal gammopathy in 90 patients of 2-29 years old so that 38 percent of them had hyper gamma globulinemia that their most preferable one was isolation of IgM (in 23/3 per cent of cases).
After that accompanied increase of IgA, IgM in 8/8 per cent of cases, increase of isolation of IgA in 3/3 percent of cases, increase of isolation of IgG in 2/2 per cent of cases and accompanied increase of IgA, IgM were seen in 1/1 per cent of cases. 7 patients (8/1%) had oligomonoclonal gammopathy. The incidence of oropharyngial dysphagia and aspiration have been reported in patients affected to A-T so that from 51 patients of Mr. Leftone, 14 persons (27%) have had history of dysphagia and aspiration that silent aspiration (without cough) has been in 10 persons also the amount of incidence of aspiration in older patients been more than children one so that the average age of patients with history of aspiration 16/3 years against patients without this history 10/8 years. In Italy, ataxia telangiectasia has been mentioned as one disease of it, more tries have been done for recognizing before birth in this country. In the last report of Chessa, a sample of placental villosity are pregnant from one pregnant 37 years old woman that has had two children affected to A-T and two stimulated abortion and found mutation in two affected children is searched. Even differential scanning calorimetry and quantitative fluorescence microscopic are done for determining the construction of chromatin in taken lymphoblastoid cell from a patient affected to ataxia telangiectasia and its comparison with a health member of family. And one sever non concentration of core chromatin has been seen in affected patient. This patient is the most prevalent reason of ataxia accompanied with brain degeneration. Earlier start of ataxia in 3-20 years old is considered as initial founding of disease. These signs are improved so those cause disability of patient during maturity. Other main signs of disease are eye signs of patients almost in forms of transversal nystagmus and coulometer apraxia that are relative prevalent and helpful. Dermal signs are appeared generally after nervous signs between 1-2 years and around 3-6 years in the form of telangiectasia on eye and then nose, cheeks, auricle and finally one limbs in a part that exposes to light with decrease of elasticity (like scleroderma).
In discussed patient, the symptoms of disease have been begun from ages of 4-5 years old with repeated respiratory infections and change of move including shaking of limbs and disability in walking have been gradually appeared. The nervous signs & move disorder have been continued progressively so that after 2 years, the patient becomes disabling. After one year, leaping moves of eyes that have been not controllable are increased. And venous damages have been appeared firstly at eyes, then on skin of nose, cheeks, and other parts of body. With an unclear reason in this disease, chance of affection to lymphoreticular (leukemia, lymphoma, Hodgkin) and brain tumors are about 50-100 equal to normal persons. Our patient refereed in 13 years old with signs of fever, fade ness, progressive weakness, cervical lymphadenopathy, hepatosplenomegaly, anemia, thrombocytopenia, leucocytosis and existence of 70% of last in environmental blood that were confirmed in considering marrow affected to acute Lymphoblastic leukemia.
The reason of death of these patients is mainly affection to infectious diseases or spread of cancer. In our patient, as seen, the reason of death was existence of infection and expansion of leukemia with acute cashexia. Understanding how-to of genetic situation of patient for parents and creating homozygote child are important for prevent of incidence of disease. Based on a study in America, 90 per cent of parents know that they were heterozygote with having one child affected to A-T. 84% of them had considered their own health children before their reaching to age of 18 years old in the case of this disease. With regard to family history of our patient, the feature of recessives autosomal of disease is explainable so hangers of family marriage in their family are warhead in council with parents during mentioning how-to transportation of disease.
Ataxia-Telangiectasia MUMS Mashhad university of medical sciences
Last Update : 2016-12-03 15:03:34