Muscle power is reduced little if at all until late in the illness, but tendon reflexes may disappear. The characteristic telangiectatic lesions, which are mainly transversely oriented subpapillary venous plexuses, appear at 3 to 5 years of age or later (they are not apparent in some patients until approximately age 7) and are most apparent in the outer parts of the bulbar conjunctivae (Fig. 37-13), over the ears, on exposed parts of the neck, on the bridge of the nose and cheeks in a butterfly pattern, and in the flexor creases of the forearms. Vitiligo, café-au lait spots, loss of subcutaneous fat, and premature graying of hair are observed in some older patients. Many of the patients have endocrine alterations (absence of secondary sexual development, glucose intolerance). The disease is progressive, and death may occur in the second decade from intercurrent bronchopulmonary infection or neoplasia—usually lymphoma, less often glioma, that develop in fewer one-third of patients.
As mentioned, the adult form of ataxia-telangiectasia, in which some of the deficient enzyme activity is retained (see below), manifests few telangiectasias but may be identified by an extrapyramidal syndrome in childhood and only later, with mild ataxia as summarized by Verhagen and colleagues; there may be a family history of cancers.
The significant abnormalities in the CNS are severe degeneration in the cerebellar cortex (visible on MRI); loss of myelinated fibers in the posterior columns, spinocerebellar tracts, and peripheral nerves; degenerative changes in the posterior roots and cells of the sympathetic ganglia; and loss of anterior horn cells at all levels of the spinal cord. In a few cases, vascular abnormalities, like the mucocutaneous ones, have been found scattered diffusely in the white matter of the brain and spinal cord, but they are of questionable significance. Also, there may be a loss of pigmented cells in the substantia nigra and locus ceruleus (a feature shared with PKU), and cytoplasmic inclusions (Lewy bodies) in the cells that remain (Agamanolis and Greenstein). During early development there are abnormalities of Purkinje cell migration and variations in nuclear size. Intranuclear inclusions and bizarre nuclear formations have also been found in the satellite cells (amphicytes) of dorsal root ganglion neurons (Strich).
There is an absence or decrease in several immunoglobulins—IgA, IgE and isotypes, IgG2, IgG4—in practically every patient. These deficiencies, shown by McFarlin and associates to be a result of decreased synthesis, are associated with hypoplasia of the thymus, loss of follicles in lymph nodes, failure of delayed hypersensitivity reactions, and lymphopenia. This immunodeficient state accounts for the striking susceptibility of these patients to recurrent pulmonary infections and bronchiectasis. Transplantation of normal thymus tissue into the patient and administration of thymus extracts have been of no therapeutic value.
The defective gene (ATM) is a kinase that is a transducer in the pathway for DNA repair that halts the cell cycle after DNA damage. For this reason, there is faulty repair of DNA after radiation and a greatly increased risk of lymphomas, leukemias, and other tumors as well as certain specific susceptibilities to the effects of cancer treatment. The protein is normally expressed ubiquitously and 90 percent of patients have no ATM protein, usually because of a stop codon in the mutated gene.
The only therapy centers on the control of infections. Free radical scavengers such as vitamin E have been recommended without proof of their effectiveness. Because of radiation sensitivity, even conventional diagnostic tests (dental, chest radiography) should be avoided unless there is a compelling reason for them.