Wilson Disease Comorbid with Hereditary Sensory Autonomic Neuropathy Type IV and Gitelman Syndrome / 대한소아소화기영양학회지

Wilson disease a rare autosomal recessive inherited disorder of copper metabolism, is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if it is not recognized early and treated when it is symptomatic. Gitelman syndrome is also an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. Hereditary sensory autonomic neuropathy type IV (HSAN-IV), a very rare condition that presents in infancy, is characterized by anhidrosis, absence of pain sensation, and self-mutilation. It is usually accompanied by developmental delay and mental retardation. We report a case of Wilson disease manifested as fulminant hepatitis, acute pancreatitis, and acute kidney injury in a 15-year-old boy comorbid with HSAN-IV and Gitelman syndrome. Such concurrence of three genetic diseases is an extremely rare case.

Biological Analysis of a New Spontaneous Mutant Mouse Showing Deafness and Circling Behavior / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Deafness is the most common sensory deficit and hereditary defect in human populations. The present study investigated the causative gene in circling mice using the complementation test. In addition, the phenotypes and histopathologic findings in circler mice, spinner mice, and compound heterozygote mice were analyzed to elucidate the mechanism of causative gene in inner ear deafness. MATERIALS AND METHOD: In order to analyze inner ear pathology in time sequence for the circler mice, spinner mice, and compound heterozygote, five groups of the homozygous mutants of different ages were used: 10, 18, 21, 35, and 90 days old. The organs of Corti and spiral ganglion neurons in the basal and middle turns were included for quantification. For the preparation of genomic DNA, tail tissues were used. RESULTS: The hair cells in the organ of Corti degenerated in a time-dependent manner. In the basal and middle turns, the volume ratio of spiral ganglion neurons significantly decreased as the mutant aged. RT-PCR analysis indicated that transmembrane inner ear (Tmie) was absent in the case of circler mice, similar to spinner mouse of which is defective Tmie gene. Therefore the variations may be a result from strain-specific allelic differences of the Chr 9 Tmie gene itself (allelic heterogeneity). CONCLUSION: The cir mutant is a suitable mouse model for neuroepithelial defects. PCR and RT-PCR analyses suggest that the Tmie transcript is absent in circler mice. This model represents another candidate for human genetic hearing loss.