Head turns faster than eye movements when gazing at fast-moving objects
Introduction
Introduction A typical manifestation of pediatric ataxia telangiectasia syndrome is that when the patient looks at a fast moving subject, the head rotates faster than the eye movement. According to the principle of null alleles, different forms of mutation can lead to great differences in clinical phenotype, from the typical ATS clinical phenotype to no clinical symptoms. Ataxia telangiectasia syndrome is a group of multiple systemic autosomal recessive hereditary diseases, also known as Louis Bar syndrome. The main clinical features are cerebellar syndrome and facial skin, conjunctival telangiectasia; children Sensitive to ionizing radiation, defective T cell function, prone to repeated respiratory infections.
Cause
Cause
Ataxia telangiectasia syndrome is a group of multiple systemic autosomal recessive hereditary diseases, also known as Louis Bar syndrome. The main clinical features are cerebellar syndrome and facial skin, conjunctival telangiectasia; children Sensitive to ionizing radiation, defective T cell function, prone to repeated respiratory infections.
Examine
an examination
Related inspection
Neurological examination EEG examination
(1) Causes of the disease
The disease (ataxia telangiectasia mutated, ATM) gene is located on chromosome 11q22~23 and contains 66 exons. From amino to carbon, it can be divided into ATM, open reading frame (ORF) and phospholipid inositol 3-kinase. Three regions (phosphatidylinositol 3-kinases, PI3-kinase).
Untranslated regions (UTRs) of the ATM gene have a wide range of mutation sites, involving three regions of ATM, ORF and PI-3 kinase. 70% of the ATM gene mutations that cause ATM protein inactivation are large fragment deletions, and other mutant forms have insertions, in-frame deletions, and nonsense mutations that block splicing.
(two) pathogenesis
As a PI3-kinase-associated family, ATM proteins are involved in cell cycle regulation, intracellular protein transport, and DNA damage.
When cells are exposed to radiation, the main function of the ATM protein is to keep the cell cycle in a stationary phase, giving the damaged DNA a chance to be repaired. ATM maintains the stability of p53 through the phosphorylation pathway and binds to the protein tyrosine kinase c-Abl as a complex to regulate the cell cycle. Mutations in the ATM gene keep the damaged cells in a cleavage phase. The damaged DNA is not repaired and the rupture is more likely to occur during the cell division. Cellular telomeres are shortened, leading to apoptosis. This may explain the high sensitivity to radioactivity in patients with ataxia telangiectasia syndrome and progressive cerebellar ataxia induced by cerebellar Purkinje cell death.
According to the principle of null alleles, different forms of mutation can lead to great differences in clinical phenotype, from the typical ATS clinical phenotype to no clinical symptoms.
Diagnosis
Differential diagnosis
1. Neurological manifestations: Ataxia occurs in 20% of those within 1 year old, 65% of 2 years old, 85% of 4 years old, and a few cases can be delayed until 4 to 5 years old. The condition progressed slowly but was progressive, eventually leading to severe dyskinesia. The typical performance is that when the patient looks at a fast moving object, the head rotates faster than the eye movement. In some cases, mental retardation occurs, but most patients have normal intelligence and vital functions before the age of 20 or 30.
2. Eye and skin telangiectasia: telangiectasia occurs earliest in the ball-bound membrane and occurs between the ages of 1 and 6 years. With age, telangiectasia is more pronounced and occurs in other areas, such as the nasal side, ears, posterior forearm and leg bends, and the back of the hands and feet.
3. Repeated infection: Repeated pulmonary infection can lead to chronic bronchiectasis, which can occur before ataxia and telangiectasia. Patients are prone to concurrent viral or bacterial infections, but unlike other immunodeficiency diseases, ATS patients rarely have opportunistic infections.
4. Endocrine abnormalities: ATS patients who survive to adolescence may have no secondary sexual characteristics. Some male patients have testicular and female ovarian atrophy, and growth arrest may occur as the disease progresses. Insulin-resistant diabetes may be associated with insufficient insulin receptors or reduced affinity. It has recently been found that ATM mutations affect the intracellular signaling of glucose in the PI3-kinase pathway and are responsible for the development of insulin resistance diabetes.
5. Malignant tumors: The incidence of cancer in patients with ATS (homozygous) is about 100 times higher than that of healthy peers. The most common tumors are proliferative malignancies of the lymphatic system, and others include adenocarcinoma, germblastoma, reticulocyte carcinoma, and myeloma and neurological malignancies. The symptoms of atypical cases and mild patients are late, clinical progression is slow, and radiosensitivity is diminished.
According to the clinical manifestations and immunological examination can be diagnosed, the foreign application of ATM3BA antibody immuno-hybrid method directly detects the mutant ATM gene for diagnosis. Some patients begin to develop ataxia, without telangiectasia and immunodeficiency, requiring long-term follow-up, sometimes only a few years after the typical performance.
