[Molecular analysis of peroxisomal disorders]
Department of Pediatrics, Gifu University School of Medicine.
Peroxisome biogenesis disorders (PBD) include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). They are classified into ten complementation groups. Five pathogenic genes have been identified using different model systems of peroxisome deficient mutants. PAF-1 and 2 were identified from CHO mutants and were responsible genes for PBD group F and C. Human PEX 5, 12 and 1, responsible genes for group 2, 3 and 1, respectively, were cloned by homology search between yeast PEX genes and human genes on the cDNA data base. Adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder, shows phenotypic heterogeneity. Its responsible gene was cloned by positional cloning. It encodes a 75 kDa peroxisomal membrane protein (ALDP) that is a member of the ATP-binding cassette transporter family. There are about 120 different mutations including missense, nonsense and splice mutations, as well as insertions and deletions of a few base pairs. There is no correlation between the clinical phenotype and the ALDP gene mutation. Recently, animal models have been produced by targeted mutation of the PBD and ALD genes. The mouse model should facilitate researches on PBD and ALD, especially those on regulatory factors of their phenotypic heterogeneity and on new therapeutic approaches.
[Improvement of QOL by advance in the management of respiratory disorders, dysphagia and upper gastrointestinal disorders in children with severe cerebral palsy]
Department of Pediatrics, National Rehabilitation Center for Disabled Children, Tokyo.
In children with severe cerebral palsy, the daily use of naso-pharyngeal airway, daily chest physiotherapy and adequate posture control markedly improve respiratory disorders and their consequent complications. Non-invasive ventiratory support methods such as nasal IPPV and nasal CPAP can be also effective. Enteral feeding through a naso-jejunal catheter can successfully manage feeding difficulty due to gastroesophageal reflux when surgical treatment is difficult. Exact assessment of aspiration by adequately performed video-fluoroscopic swallowing examination leads to national management of dysphagia. Tube feeding by intermittent oro-gastric catheterization combined with oral feeding is useful way in many dysphagic children. Surgical treatment for prevention of aspiration markedly improves the general condition. These treatments and managements have markedly improved the QOL, of children with severe cerebral palsy in many aspects. Cooperation of pediatricians, parents, school teachers and other community staffs is necessary for appropriate daily management of medical problems of these children.