A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.

No abstract

In advanced cases of superficial siderosis of the human central nervous system, the clinical triad of hearing loss, cerebellar ataxia, and myelopathy permits the diagnosis at the bedside, and magnetic resonance imaging readily confirms the hemosiderin deposits in brainstem, cerebellum, and spinal cord. To study the pathogenesis of this condition and explain the selective vulnerability of the cerebellum, experimental siderosis was induced in rabbits by the repeated intracisternal injection of autologous red blood cells. The earliest cellular response in the cerebellar molecular layer was hyperplasia and hypertrophy of microglia as displayed by immunocytochemistry for ferritin. Microglia also contained iron, but ferritin biosynthesis appeared to proceed without commensurate iron accumulation. This early apoferritin response probably occurred due to the presence of heme, rather than iron, in the cerebrospinal fluid and subpial tissue. Ferritin biosynthesis is accelerated when the ferritin repressor protein is dissociated from ferritin messenger ribonucleic acid. A specific antiserum localized ferritin repressor protein predominantly to astrocytes including Bergmann glia. It is proposed that abundance and proximity of ferritin repressor protein--immunoreactive Bergmann glia and ferritin-containing microglia in the cerebellar molecular layer permit prompt cellular interaction in the conversion of heme to ferritin and ultimately hemosiderin.