No abstract

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains 95% of the copper found in the plasma of vertebrate species. We report here on the identification of a genetic defect in the ceruloplasmin gene in a patient previously noted to have a total absence of circulating serum ceruloplasmin in association with late-onset retinal and basal ganglia degeneration. In this patient T2 (transverse relaxation time)-weighted magnetic resonance imaging of the brain revealed basal ganglia densities consistent with iron deposition, and liver biopsy confirmed the presence of excess iron. Although Southern blot analysis of the patient's DNA was normal, PCR amplification of 18 of the 19 exons composing the human ceruloplasmin gene revealed a distinct size difference in exon 7. DNA sequence analysis of this exon revealed a 5-bp insertion at amino acid 410, resulting in a frame-shift mutation and a truncated open reading frame. The validity of this mutation was confirmed by analysis of DNA from the patient's daughter, which revealed heterozygosity for this same 5-bp insertion. The presence of this mutation in conjunction with the clinical and pathologic findings demonstrates an essential role for ceruloplasmin in human biology and identifies aceruloplasminemia as an autosomal recessive disorder of iron metabolism. These findings support previous studies that identified ceruloplasmin as a ferroxidase and are remarkably consistent with recent studies on the essential role of a homologous copper oxidase in iron metabolism in yeast. The clinical and laboratory findings suggest that additional patients with movement disorders and nonclassical Wilson disease should be examined for ceruloplasmin gene mutations.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism resulting in neurodegeneration of the retina and basal ganglia. We report here on the treatment of a patient who developed progressive extrapyramidal symptoms that included blepharospasm, grimacing, and rigidity associated with increased iron deposition in the brain and visceral organs. Treatment for 10 months with the iron chelator desferrioxamine decreased brain iron stores, prevented progression of the neurological symptoms, and reduced plasma lipid peroxidation. These data suggest that early treatment with this chelator may be useful in such patients to diminish central nervous system iron accumulation and to prevent or ameliorate neurological symptoms associated with neurodegeneration.

Karojisatsu in Japan: Characteristics of 22 Cases of Work-Related Suicide: Takashi AMAGASA, et al. Mental Clinic Misato-With the rapidly increasing number of work-related suicides in Japan (Karojisatsu, in Japanese), both applications for worker's compensation insurance and civil suits are proliferating. The phenomenon of work-related suicide is examined along with the process and related factors. With informed consent from bereaved families, two certified psychiatrists independently reviewed and summarized 22 insurance and legal reports filed by psychiatrists on employee suicides that were related to heavy workloads. A clinical epidemiologist participated in discussions with psychiatrists to reach a consensus concerning the cause of the suicides. Only one case involved a female. Seventeen had experienced personnel changes, such as a promotion or transfer. Low social support was recognized in 18, high psychological demand in 18, low decision latitude in 17, and long working hours in 19 cases (more than 11 hours per day for 3 months or more, and without a day off in 9). The subjects had depressive episodes by the ICD-10 criteria and showed suicidal signs. Ten of them saw a general practitioner because of unspecified somatic complaints, but no effective measures were taken. None of them had a history of psychiatric consultation or had received mental health education dealing with job stress management. Although causality cannot be made from this case series report, we hypothesize that long working hours, heavy workloads, and low social support may cause depression, which can lead to suicide. Appropriate countermeasures are urgently needed and the present findings suggest some of them are possible. (J Occup Health 2005; 47: 157-164)

The present results reveal a significant difference in the mean phase duration of binocular rivalry between subjects with BD-I and those with BD-II, suggesting the presence of some neurobiological difference between these two subtypes of bipolar disorder.

Although individuals aged 65 and over accounted for 12% of the total population of Japan in 1990, suicides in this age group consisted of 29% of all suicides. The elderly population of Japan is expected to grow rapidly to 24% of the total population by the year 2020, and suicide prevention for the elderly is an urgent mental health problem. Among a total of 1,216 elderly patients who were admitted to the Department of Psychiatry at Tokyo Metropolitan Geriatric Hospital between April 1980 and March 1990, 50 were hospitalized immediately after suicide attempts in order to study their psychosociomedical problems. Because early diagnosis of depression and initiation of proper treatment are indispensable—even if patients do not show obvious depressive symptoms—those who develop persistent somatization and/or delirium should be considered highly suicidal and given special attention. With the cooperation of mental health professionals, it is necessary to educate general practitioners, the public, and the elderly themselves about characteristics of psychiatric disorders and various problems associated with aging. Further research on other elderly Japanese populations, as well as research that examines suicide completion, is needed to confirm the findings of the present study.

No abstract

We report here on the characterization of a mutation in the ceruloplasmin gene in a 45 year old woman with insulin-dependent diabetes mellitus who presented with the recent onset of gait disturbance and dysarthria. Physical examination revealed an ataxic gait, scanning speech and retinal degeneration. Magnetic resonance imaging of the brain was consistent with increased basal ganglia iron content and laboratory studies revealed a low serum iron concentration and no detectable serum ceruloplasmin. Nucleotide sequence analysis of the ceruloplasmin gene from this patient revealed a G to A substitution in exon 15 resulting in a nonsense mutation at amino acid 858 (Trp858ter). The patient's younger, neurologically asymptomatic brother was also found to be homozygous for this mutation. Taken together the clinical and genetic data support the concept of an essential and unique role for ceruloplasmin in human iron metabolism. Identification of this kindred extends the spectrum of ceruloplasmin gene mutations resulting in this autosomal recessive, late-onset neurodegenerative disease and highlights the importance of recognizing aceruloplasminemia as a genetic cause of diabetes and neurologic disease.