Tuberous sclerosis complex (TSC) is a genetic, variably expressed, multisystem disorder that can cause circumscribed, benign, noninvasive lesions in any organ (Curatolo 2003; Gomez 1999). It affects about 1 newborn in every 6000 (Osborne, Fryer et al. 1991). The term tuberous sclerosis of the cerebral convolutions was used more than a century ago to describe the distinctive findings at autopsy in some patients with seizures and mental subnormality; the term tuberous describes the potato-like consistency of gyri with hypertrophic sclerosis (Bourneville 1880). The wide range of organs affected by the disease implies an important role for the TSC1 and TSC2 genes encoding hamartin and tuberin in the regulation of cell proliferation and differentiation. Tuberous sclerosis complex is a protean disease: the random distribution, number, size, and location of lesions cause varied clinical manifestations, involving the brain, skin, eyes, heart, kidney, lung (Curatolo et al. 2008). Some lesions, such as renal angiomyolipomas, do not occur until a certain age; by contrast, cardiac rhabdomyomas appear in the fetus and almost always regress spontaneously in infancy (Sosunov et al. 2008). About 85% of children and adolescents with TSC have central nervous system (CNS) manifestations, including epilepsy, learning difficulties, mental retardation, challenging behavioral problems, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), which can be associated with the structural CNS features generally seen in TSC (Curatolo et al. 1991; Gillberg et al. 1994). Abnormalities of neuronal migration and cellular differentiation, and excessive cell proliferation, all contribute to the formation of the various TSC brain lesions including cortical tubers, subependymal nodules (SENs), subependymal giant cell astrocytomas (SEGAs), and widespread gray and white matter abnormalities, these latter being identified even in patients with average intelligence (Ridler et al. 2001; de Vries et al. 2005; Ridler et al. 2007). Further characterization of these typical lesions has been provided by progress in structural and functional imaging (DiMario 2004; Luat et al. 2007). Major and minor criteria exist to diagnose TSC (Table 32.1). The diagnosis is made when two major features, or one major and two minor ones, can be detected.
Abnormal glycogen storage in tuberous sclerosis complex caused by impairment of mTORC1-dependent and -independent signaling pathways
