Persistence of very high serum levels of oncofetal proteins, including a-fetoprotein and carcinoembryonic antigen, may be of diagnostic value. Frequent causes of death are chronic pulmonary disease and malignancy. Lymphomas are most common, although carcinomas also occur. The immunologic abnormalities seem to be related to maldevelopment of the thymus. The markedly hypoplastic thymus is similar in appearance to an embryonic thymus. The peripheral T cell pool is reduced in size, especially in lymphoid tissue compartments. Cutaneous anergy and delayed rejection of skin allografts are common.
     Although B lymphocyte development is normal, most patients are deficient in serum IgE and IgA, and a smaller number have reduced serum levels of IgG, particularly of the IgG2, IgG4 subclasses. The defect in DNA repair mechanisms in AT patients renders their cells highly susceptible to radiation-induced chromosomal damage and resultant tumor development. AT is a rare disorder, with an incidence of 1 in 10,000 to 1 in 100,000, but 1% of the population is heterozygous for an AT mutation. This is important because the heterozygous state also predisposes to enhanced cellular radiosensitivity and cancer, especially breast cancer in females.

SYMPTOMS AND SIGNS
Patients with ataxia telangiectasia (AT) present in the first decade of life with progressive telangiectatic lesions associated with deficits in cerebellar function and nystagmus. The neurologic manifestations correspond to those in Friedreich’s disease, which should be included in the differential diagnosis. Truncal and limb ataxia, dysarthria, extensor plantar responses, myoclonic jerks, areflexia, and distal sensory deficits may develop. There is a high incidence of recurrent pulmonary infections and neoplasms of the lymphatic and reticuloendothelial system in patients with AT.

     Thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies, premature aging, and endocrine disorders such as type 1 diabetes mellitus are described. There is an increased incidence of lymphomas, Hodgkin’s disease, acute leukemias of the T cell type, and breast cancer. The most striking neuropathologic changes include loss of Purkinje, granule, and basket cells in the cerebellar cortex as well as of neurons in the deep cerebellar nuclei. The inferior olives of the medulla may also have neuronal loss.

     There is a loss of anterior horn neurons in the spinal cord and of dorsal root ganglion cells associated with posterior column spinal cord demyelination. A poorly developed or absent thymus gland is the most consistent defect of the lymphoid system.

EPIDEMIOLOGY & DEMOGRAPHICS
Rare, autosomal recessive with abnormalities in chromosome 14. The defective gene product is ATM, a protein kinase.

PHYSICAL FINDINGS & CLINICAL PRESENTATION
Child will have initial abnormalities in walking (awkward, unsteady). Patients have recurrent pulmonary infections.

Ataxia Telangiectasia

Ataxia-telangiectasia (AT) is an autosomal recessive genetic disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, and immunodeficiency. The mutant ATM gene has sequence similarity to the phosphatidyl-inositol-3 kinases that are involved in signal transduction. The ATM gene belongs to a conserved family of genes that monitor DNA repair and coordinate DNA synthesis with cell division. The deleterious effects of the ATM gene are widespread. Truncal ataxia may become evident when walking begins and is progressive. Telangiectasia, primarily represented by dilated blood vessels in the ocular sclera, in a butterfly area of the face, and on the ears, is an early diagnostic feature. Immunodeficiency may be clinically manifest by recurrent and chronic sinopulmonary infection leading to bronchiectasis, although not all patients have overt immunodeficiency. Ovarian agenesis is a frequent occurrence.