Hereditary progressive dystonia with marked diurnal fluctuation (Segawa syndrome) in Taiwan.

Since 1988, we have diagnosed 6 cases of hereditary progressive dystonia with marked diurnal fluctuation (HPD) in Taiwan. All cases presented with clinical features similar to those described by Segawa. They consisted of four sporadic and two familial cases. The age at onset ranged from 18 months to 8 years. There is a female predominance of 4:2. All of them showed mild postural tremor and postural dystonia manifested initially by flexion-inversion of a foot. However, unlike Segawa's description, side preference to the right (4:2) was noticed. Neck and axial muscles were not or were minimally involved, except a case presenting with retrocollis and tilting of the neck. These symptoms showed remarkable diurnal fluctuation which became aggravated towards the evening and alleviated in the morning or after rest. Response to L-dopa was dramatic, independent of the duration of illness, and no adverse effect of L-dopa has been observed. Our experience suggested that 10 mg/kg/day of L-dopa may be an optimally effective dose for treatment of patients with HPD. Neurophysiological, neuroradiological and biochemical studies were all normal except in one case who showed prolonged somatosensory potential latencies and white matter changes on MRI. Change of dopamine and its metabolites in CSF, plasma and urine had been investigated in one case.

Galatosialidosis (beta-galactosidase-neuraminidase deficiency): clinical and biochemical studies on 13 patients.

Thirteen patients with galactosialidosis (beta-galactosidase-neuraminidase deficiency) from 9 families including two autopsy cases were studied from clinical, genetic, cytological and biochemical standpoints. Coarse facies, myoclonus, cerebellar ataxia, angiokeratoma, loss of vision, corneal opacity and cherry-red spots were the main signs and symptoms although these clinical manifestations were widely variable in individual cases. It is not yet known whether these clinical variations represent genetic heterogeneity or not. Deficiency of beta-galactosidase and neuraminidase was the most prominent biochemical abnormality in this disease. Beta-Galactosidase activity was restored in fibroblasts when serine-thiol protease inhibitors were added to the culture medium. Cathepsin B activity was significantly high in fibroblasts, liver and brain from the patients. It was demonstrated that neuraminidase was susceptible to the procedures for disrupting cells and tissues, such as sonication and freezing. The stability of this enzyme may be dependent on the molecular state in relation to cell membranes.

[CHARGE association: report of a case with literature review].

The CHARGE association was described as a cluster of multiple congenital defects by Pagon et al in 1981. The underlining cause of this association is not yet clear. These defects include coloboma of the eye tissues (C), heart disease (H), atresia choanae (A), retarded growth and development and/or CNS anomalies (R), genital anomalies (G), ear anomalies and/or hearing loss (E). Here we report a case of CHARGE association in a 15-year-old female patient. She presented with unilateral ptosis and coloboma of the iris, choroid and retina, patent ductus arteriosus, growth and mental retardation, unilateral ear deformity and a hearing loss. A total of 124 cases have been reported up to now in the literature. We also discuss the frequency of the respective clinical symptoms and signs, and the leading causes of misdiagnosis. We emphasize the importance of ophthalmology and ENT consultations whenever a patient is noted to have multiple congenital anomalies, especially when a cardiac defect is present. Early diagnosis and treatment are essential for this rare association.

Type C Niemann-Pick disease: report of a Chinese case.

We report on a 12-year-old Chinese child with type C Niemann-Pick disease, who presented primarily with neurologic symptoms. He started to develop ataxia and dysarthria at the age of six years. Dementia, dysphagia, dystonia and seizures, in that sequence, followed within a couple of years. He was anarthric and bedridden five years after onset. Supranuclear vertical gaze palsy was found at the beginning of the illness. However, no hepatosplenomegaly or other physical abnormality was noted. Bone marrow aspirates revealed foamy storage cells and sea-blue histiocytes. However, sphingomyelinase activity in the cultured skin fibroblast was normal. The characteristic clinical presentations and typical pathologic and histochemical findings meet the diagnostic criteria of type C Niemann-Pick disease. We report the first Chinese case of type C Niemann-Pick disease and review 73 cases reported previously.

[Clinical and cellular biologic diagnosis of Cockayne syndrome: a case report].

We report a case of Cockayne syndrome. A 6-year-old boy presented with a progeroid face, dwarfism, psychomotor retardation, skin photosensitivity and retinal pigmented degeneration. Neurological study disclosed slowed nerve conduction velocities and a brain CT showed calcification in the basal ganglia. Auditory brain stem evoked potential showed prolonged interpeak latency of wave I to wave V. Laboratory evaluation revealed mild liver dysfunction and peripheral eosinophilia. Fibroblast cultures from the patient and his family were exposed to ultraviolet (UV) light of 254 nm, ranging from 1 to 10 J/m2. Under 1 J/m2 irradiation, the surviving fraction of the fibroblasts from the patient, his mother, and a control subject were 40%, 50%, 90% respectively. If the fibroblasts of these subjects were exposed to 2 J/m2 and 3 J/m2 irradiation, the surviving fraction changed to 10%, 22%, 80% and 1.5%, 9%, 68%, respectively. However, fibroblasts from his sister and father showed the same surviving fraction as the control. The study showed that fibroblasts from the patient and his mother were extremely sensitive to UV light irradiation. We also study the concentration of the pyrimidine dimer of DNA in the patient and the control subject. Pyrimidine dimer showed no difference between the patient and the normal subject before and after 24-hour UV irradiation. These results suggest that the sensitivity to UV of Cockayne fibroblasts may be due to a ligase deficiency or to a replicon initiation disturbance in Cockayne cells.

Chronic progressive external ophthalmoplegia with NADH-CoQ reductase deficiency: report of a case.

A thirty-two year old female had chronic progressive external ophthalmoplegia (CPEO), exertional fatigue, dysarthria, dysphagia, and bilateral hearing impairment. Histochemical stains, obtained from the right vastus lateralis, showed ragged-red fibers and wide-spread abnormalities in the number, size, and the structure of mitochondria under electronomicroscopic examination. A biochemical analysis showed a low activity of NADH-cytochrome C reductase, NADH dehydrogenase and a normal activity of succinate cytochrome C reductase and cytochrome C oxidase. This data suggests a specific defect in the NADH dehydrogenase of complex I (NADH CoQ reductase). We believe that this is the first biochemically defined mitochondrial myopathy reported in Taiwan and provides additional evidence for the existence of biochemical heterogeneity in mitochondrial disorders of CPEO.

Effects of thiol protease inhibitors on intracellular degradation of exogenous beta-galactosidase in cultured human skin fibroblasts.

The effects of low molecular weight (LMW) protease inhibitors of microbial origin were evaluated on the intracellular degradation of beta-galactosidase purified from Aspergillus oryzae and taken up by cultured human skin fibroblasts with beta-galactosidase deficiency. Only thiol protease inhibitors showed an effect to increase the enzyme activity. E-64, a specific inhibitor of thiol proteases, prolonged 3-fold a half life of the exogenous beta-galactosidase and when the enzyme was supplied as liposomes, the half life was prolonged 9-fold in these cells. The role of thiol proteases in the degradation of enzyme molecules was discussed.

[Osteogenesis imperfecta: report of two cases].

Osteogenesis imperfecta (OI) is a heterogenous group of inherited conditions arising from a variety of biochemical and morphological collagen defects. We report 2 cases with a clinical diagnosis of OI. The first case was classified as Silence type IIA. He was delivered at 38 weeks' gestation with severe bowing of long bones, blue sclera and craniotabes at birth. Radiographs showed severe generalized osteoporosis, broad and crumpled long bones, beading ribs and poorly mineralized skull. Histological examination of the long bones revealed the trabecula of the calcified cartilage with an abnormally thin layer of osteoid & the bony trabeculae were thin and basophilic. The second case was classified as Sillence type III. She was delivered at 39 weeks' gestation. Short, bowed lower extremities but normal color of sclerae were noted after birth. Radiographs revealed L't femoral fracture and callus formation of R't 8th rib. She survives till now with gradual deformity of long bone and growth retardation. Because of the poor prognosis of Sillence type II and type III, there is no doubt that accurate genetic counseling and prenatal diagnosis will become important in the management of the disease.

Modern aspects of hygienic standardization of ship noise.

The basic aims of hygienic standardization of the long-term round-the-clock action of ship noise on the sailors include protection of health, prolonged professional activity, prevention of interference and provision of comfort conditions of rest. Neuro-emotional stress in the work of sailors aboard a ship has been another reason for starting the ship noise standardization. As a result of long-term hygienic, clinical, physiological, experimental and natural studies, there were established the hygienic significance of noise and vibration parameters, a combined increased effect of noise and work strain, as well as that of pitching and rolling, and also the potent combined effect of vibration and noise. During a 3-month voyage the cumulative effect of noise was identified and the physiological significance of acoustic comfort of post-watch rest was ascertained. The relation of sailors' health to ship acoustic conditions was determined. The obtained results served as a scientific motivation for a number of Soviet legislative documents. Unification of physiological and hygienic criteria and methods of assessment of noise and vibration effects meets the interests of protection of seamen's health in CMEA countries.