Pathological consequences of copper deficiency and cobalt deficiency

Aspects of the pathology of copper deficiency in several species, and cobalt deficiency in sheep, are summarized. An attempt is made to interpret morphological changes in copper-deficient animals in terms of biochemical defects. The common denominator may be mitochondrial lesions, with a generalized effect on energy-dependent synthetic functions of the cell. In copper deficiency, such defects can be attributed to depletion of copper-dependent enzymes, while deficiency of cobalt in ruminants is, in effect, deficiency of vitamin B12. The pathological consequences of vitamin B12 deficiency form a syndrome, notable features of which are neurological and muscular lesions, in which the metabolic consequences of hepatic damage may play a significant role.     

IGF-I deficiency due to GH receptor deficiency.

IGF-I deficiency may be primary due to defective synthesis, or secondary to GH receptor deficiency (GHRD) or defects in transduction of the GH-GHR signal. Cloning and sequencing of the GHR led to recognition that circulating GH binding protein (GHBP) was structurally identical to the extra-cellular domain of the GHR, and the identification of 33 mutations of the GHR in approximately half of the 250 patients that have been reported. This review explores the information provided about GHR function by various mutations, the population distribution of GHRD, the effects of this condition on mortality, growth, development, and metabolism, the effects of replacement therapy with recombinant human IGF-I, diagnostic issues, and the question of partial GH resistance.     

Prostaglandin deficiency

Healthy cells from virtually all tissues synthesize a variety of prostaglandins, autacoids which can significantly alter cellular functions. An absolute or relative deficiency of prostaglandins has now been demonstrated in many diseases or clinical conditions. These include 'natural' disorders such as peptic ulcer disease and diabetes mellitus. These also include 'acquired' or iatrogenic conditions such as cyclosporine nephrotoxicity and the gastropathy induced by nonsteroidal anti-inflammatory drugs. We believe that the diversity of the disorders associated with prostaglandin deficiency may be wider and of greater pathogenetic importance than is currently recognized. We propose: 1) that prostaglandin deficiency will be demonstrated in many abnormalities which are now described as of uncertain etiology; and 2) that adverse effects from many commonly prescribed drugs may also be related to an unrecognized and unfavorable alteration in prostaglandin synthesis, disposal, or activity.     

Iron deficiency

Iron deficiency and anemia affect a substantial portion of the world’s population, provoking severe health problems to the people suffering these conditions, as well as important economic losses to the regions in which this nutritional deficiency is significant. In this work, the principal causes and consequences produced by this deficiency are discussed, as well as the different strategies that can be applied in order to prevent and solve this nutritional problem.     

Placental steroid deficiency: association with arylsulfatase A deficiency

A family with an obstetric history consistent with placental sulfatase deficiency has X-linked ichthyosis. Steroid sulfatase deficiency was confirmed in placenta, leukocytes, and cultured skin fibroblasts of affected males; arylsulfatase A diminution was also observed in these tissues of both affected males and 2 generations of related females. No symptoms of metachromatic leukodystrophy are present in any family members. In this family, placental sulfatase deficiency, and arylsulfatase A pseudodeficiency are nonallelic.     

Phosphorylase kinase deficiency

Phosphorylase kinase deficiency in I strain mice and in humans both show X-chromosomal inheritance. Neither deficient adult humans nor deficient mice show any sign of disease. Thus the two conditions resemble each other. However, there are differences. The enzyme is only partially deficient in human patients in liver, muscle, and blood cells; in mice the deficiency is complete and seems to be confined to the muscles.This paper was presented at a symposium entitled Genetic Control of Mammalian Metabolism held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.Supported by grant AM 13359 of the National Institutes of Health.     

Dopamine beta-hydroxylase deficiency

Idiopathic chronic eosinophilic pneumonia (ICEP) is characterized by subacute or chronic respiratory and general symptoms, alveolar and/or blood eosinophilia, and peripheral pulmonary infiltrates on chest imaging. Eosinophilia is present in most cases, usually in excess of 1000/mm³. In absence of significant blood eosinophilia, a diagnosis of ICEP is supported by the demonstration of bronchoalveolar lavage eosinophilia. ICEP is typically associated with eosinophil counts higher than lymphocyte counts in the bronchoalveolar lavage. ICEP is a rare disorder of unknown cause. Its exact prevalence remains unknown. ICEP may affect every age group but is rare in childhood. It is twice as frequent in women as in men. One third to one half of the ICEP patients have a history of asthma. The mainstay of treatment of ICEP is systemic corticosteroids. Response to oral corticosteroid therapy is dramatic and has led to the consideration of corticosteroid challenge as a diagnostic test for ICEP. Nevertheless, relapses or development of severe asthma are frequent when tapering or withdrawing treatment. Long-term oral corticosteroid therapy is necessary in up to half of the patients.