Clinical management of Krabbe disease : Clinical Management of Krabbe Disease

Cerebral palsy (CP) is defined as motor impairment that limits activity, and is attributed to non-progressive disturbances during brain development in fetuses or infants. The motor disorders of CP are frequently accompanied by impaired cognition, communication, and sensory perception, behavioural abnormalities, seizure disorders, or a combination of these features. CP is thought to affect three to four individuals per 1000 of the general population. The incidence, prevalence, and most common causes of CP have varied over time because of changes in prenatal and paediatric care. Medical management of children and adults involves care from primary-care physicians with input from specialists in neurology, orthopaedics, and rehabilitation medicine. Physicians should also work in conjunction with rehabilitation therapists, educators, nurses, social care providers, and schoolteachers. The focus of rehabilitation treatment has recently shifted to neurological rehabilitation in response to increasing evidence for neuroplasticity. This approach aims to improve development and function by capitalising on the innate capacity of the brain to change and adapt throughout the patient's life. As the life expectancy of individuals with CP approaches that of the general population, therapies must be developed that address the needs of adults ageing with disability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Assessment of infants and children with dysphagia (swallowing problems) and feeding disorders involves significantly more considerations than a clinical observation of a feeding. In addition to the status of feeding in the child, considerations include health status, broad environment, parent-child interactions, and parental concerns. Interdisciplinary team approaches allow for coordinated global assessment and management decisions. Underlying etiologies or diagnoses must be delineated to every extent possible because treatment will vary according to history and current status in light of all factors that are often interrelated in complex ways. A holistic approach to evaluation is stressed with a primary goal for every child to receive adequate nutrition and hydration without health complications and with no stress to child or to caregiver. Instrumental swallow examinations that aid in defining physiological swallowing status are needed for some children. Successful oral feeding must be measured in quality of meal time experiences with best possible oral sensorimotor skills and safe swallowing while not jeopardizing a child's functional health status or the parent-child relationship. (c) 2008 Wiley-Liss, Inc.

The classic globoid cell leukodystrophy (Krabbe's disease) is caused by genetic defects in a lysosomal enzyme, galactosylceramidase. It is one of the two classic genetic leukodystrophies, together with metachromatic leukodystrophy. The mode of inheritance is autosomal recessive. Typically, the disease occurs among infants and takes a rapidly fatal course, but rarer late-onset forms also exist. Clinical manifestations are exclusively neurologic with prominent white-matter signs. The pathology is unique, consisting of a rapid and nearly complete disappearance of myelin and myelin-forming cells--the oligodendrocytes in the central nervous system and the Schwann cells in the peripheral nervous system, reactive astroytic gliosis, and infiltration of the unique and often multinucleated macrophages ("globoid cells") that contain strongly periodic acid-Schiff (PAS)-positive materials. A normally insignificant but highly cytotoxic metabolite, galactosylsphingosine (psychosine), is also a substrate of galactosylceramidase and is considered to play a critical role in the pathogenesis. The galactosylceramidase gene has been cloned, and a large number of disease-causing mutations have been identified. Equivalent genetic galactosylceramidase deficiency occurs in several mammalian species, such as mouse, dog, and monkey. Recently, deficiency of one of the sphingolipid activator proteins, saposin A, was demonstrated to cause a late-onset, slowly progressive globoid cell leukodystrophy at least in the mouse, with all of the phenotypic consequences of impaired degradation of galactosylceramidase substrates. Human globoid cell leukodystrophy owing to saposin A deficiency might be anticipated and should be suspected in human patients with a late-onset leukodystrophy with normal galactosylceramidase activity when other possibilities are also excluded. The only serious attempt at treating human patients is bone marrow transplantation, which can provide significant alleviation of symptoms, particularly in those patients with later-onset, more slowly progressive globoid cell leukodystrophy.