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Pathologic examination shows poor staining of myelin in the cerebral hemispheres This can be visualized by MRI in untreated children Another curious feature is that the usually pigmented nuclei (substantia nigra, locus ceruleus, dorsal vagal motor) fail to acquire dark coloration because of a block in the production of melanin Reduction in size of cortical neurons and their dendritic arborizations is said to be demonstrable in some cases Treatment If instituted in infancy, diets low but not totally lacking in PA can improve intellectual development (blood level should be maintained at 5 to 10 mg/dL) Once the neurologic picture unfolds, diet has little or no effect on the mental status but may improve behavior Prolonged dietary treatment has many untoward effects and should be supervised by physicians and nutritionists experienced in its use; if too restricted, it may retard growth This is particularly important, since it has been shown that intellectual impairment is greatest among children who were the earliest to abandon their diets, permitting the PA concentration to rise above 15 mg/dL, and least in children who maintained dietary control the longest (Holtzman et al) Continued dietary treatment is necessary With the widespread screening for PKU and the initiation of dietary control during early postnatal life, this metabolic brain disease has virtually disappeared in the New England states Treated women who reach childbearing age should be particularly careful about dietary restriction, since high levels of phenylalanine are harmful to the normal fetus Mild cases of PKU have been successfully treated with the cofactor tetrahydrobiopterin (Muntau et al) The late forms of maple syrup urine disease, histidinemia, and hydroxyprolinemia evolve in much the same fashion as PKU and raise similar problems in diagnosis and therapy A small number of infants have a variant of PKU in which a restricted PA diet does not prevent neurologic involvement In some such infants, a dystonic extrapyramidal rigidity ( stiff-baby syndrome ) has appeared as early as the neonatal period, and, according to Allen and coworkers, it responds to biopterin Such infants have normal levels of PA hydroxylase in the liver The defect is a failure to synthesize the active cofactor tetrahydrobiopterin, because of either an insuf ciency of dihydropteridine reductase or an inability to synthesize biopterin (see page 801) The urinary metabolites of catecholamines and serotonin are reduced and are not responsive to low-PA diets There is some evidence that the underlying neurotransmitter fault can be corrected by L-dopa and by 5-hydroxytryptophan (Scriver and Clow) Hereditary Tyrosinemia (Oculocutaneous Tyrosinemia; Richner-Hanhart Disease) This is a rare, predominantly dermatologic aminoacidopathy, but in approximately one-half of the infants there is a mild to moderate degree of mental retardation Also, as in some other aminoacidopathies, there may be self-mutilation and incoordination of limb movements Language defects are prominent Toward the end of the rst or second year of life, lacrimation, photophobia, and redness of the eyes (due to corneal erosions) appear Neovascularization of the corneas and opaci cation follow Palmar and plantar keratosis with hyperhydrosis and pain are frequently present as a result of an in ammatory reaction to deposits of crystalline tyrosine (also the cause of the corneal changes) Elevated tyrosine in the blood ( 018 mM) and urine are diagnostic The disease is due to a gene defect on chromosome 15 that codes for the enzyme fumarylacetoacetate hydrolase, a de ciency of which results in the accumulation of tyrosine and its metabolites A low-tyrosine and low-PA diet, optimized to allow growth.

Though understanding the hardware concepts is important, it is equally important to understand the implications of Oracle s software integration to this platform Oracle s platform support includes the operating system, Oracle Enterprise Linux, as the foundation for the database server nodes and Exadata Storage Server cells As an alternative, Oracle also offers the Solaris 11 operating system for the database server nodes Upon this platform, Oracle tightly integrates Oracle Database 11 g Enterprise Edition and extends database functionality into storage with the Exadata Storage Server Software Other Oracle database software components on the platform that are central to a typical deployment are RAC and the Oracle Partitioning Option

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FIGURE 1-14

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