Cardioskeletal mitochondrial myopathy associated with chronic magnesium deficiency.

A 3-year-old boy presenting with convulsions and carpopedal spasm had hypomagnesemia and hypermagnesuria due to congenital magnesium-losing nephropathy. Despite chronic oral and intermittent intravenous magnesium supplementation, he remained chronically hypomagnesemic. At age 4, he developed a progressive proximal myopathy and dilated hypertrophic cardiomyopathy that ultimately contributed to his death at age 14 years. Skeletal and cardiac muscle specimens showed a mitochondrial myopathy with increased numbers of enlarged, structurally abnormal mitochondria. Muscle magnesium content was markedly decreased. Chronic oral and intermittent intravenous magnesium supplementation may be inadequate to prevent the progressive cardioskeletal myopathy associated with the chronic magnesium deficiency of congenital magnesium-losing nephropathy.

Hirsutism. Pathophysiology, clinical evaluation, treatment.

Hirsutism is generally an androgen-mediated disorder. Tremendous progress has been made in elucidating the numerous clinical disorders that can cause it. Systematic evaluation of hirsute women must be directed at determining the cause of hyperandrogenemia, which in turn allows specific and effective therapy to be initiated.

Magnesium deficiency in human subjects--a personal historical perspective.

Over the past 30 years human magnesium (Mg) deficiency has become an accepted fact in most medical circles. Our index patient had striking neurological manifestations including generalized tremulousness, grimaces and fibrillary twitches of facial muscles, athetoid and choreiform movements of upper extremities, dysphagia, inability to speak, repeated convulsions, and confusion. She had received glucose in water and saline intravenously for several months. A patient with chronic alcoholism was noted to have almost identical symptoms and signs as the index patient. He also responded dramatically to MgSO4 injections. This resulted in a series of studies on patients with chronic alcoholism. The evidence of Mg deficiency in alcoholism includes the following: significant hypomagnesemia, strongly positive Mg balance during recovery, significant decrease in muscle Mg, a deficit of total exchangeable 28Mg quantitatively similar to deficit by balance studies, often a dramatic response of symptoms to therapy with Mg, and diuresis of Mg produced by ingestion of alcohol. Lipolysis with high levels of long-chain free fatty acids (FFA) occurs in withdrawal of alcohol in chronic alcoholism, withdrawal of certain addictive drugs, after trauma, surgery, administration of adrenergic compounds or theophylline, exposure to cold, and an adverse environment as in grass staggers. Concentrations of Mg fall when FFA increase in all of the above circumstances. This phenomenon has wide implications in health and disease. Better awareness of Mg deficiency in a wide variety of clinical conditions will result in life-saving treatment and less morbidity of other patients.

cis-Platinum-induced hypomagnesemia and peripheral neuropathy.

From January 1980 to September 1981, sixty-nine gynecologic oncology patients received cis-platinum at 4-week intervals. Serum magnesium was drawn prior to cis-platinum administration and then at regular intervals thereafter. cis-Platinum toxicity, especially peripheral neuropathy, was monitored closely. Forty-one patients developed hypomagnesemia; thirty-one of these patients developed signs and symptoms of peripheral neuropathy. None of the sixteen patients with normal serum magnesium levels demonstrated any evidence of neurotoxicity. Peripheral neuropathy was the major dose-limiting factor. Variables related to hypomagnesemia and peripheral neuropathy were analyzed in this patient population. It was concluded that cis-platinum-induced hypomagnesemia, as well as peripheral neuropathy, were dependent on the total dose received by a patient.

Magnesium deficiency. Etiology and clinical spectrum.

Magnesium deficiency may complicate many diseases. The causes include the following: inadequate intake during starvation or increased requirement during early childhood, pregnancy, or lactation; excessive losses of magnesium as a result of malabsorption from the gastrointestinal tract or from the kidneys during use of diuretics; and to a combination of the two, as in alcoholism. Most often the etiological factors have been operative for a month or more. Acute hypomagnesemia can occur without previous Mg deficiency after epinephrine, cold stress and stress of serious injury or extensive surgery. The clinical manifestations depend on the age of the patient and may begin insidiously or with dramatic suddenness, or there may be no overt symptoms or signs. The manifestations can be divided into the following categories: totally non-specific symptoms and signs ascribable to the primary disease; neuromuscular hyperactivity including tremor, myoclonic jerks, convulsions, Chvostek sign, Trousseau sign (rarely), spontaneous carpopedal spasm (rarely), ataxia, nystagmus and dysphagia; psychiatric disturbances from apathy and coma to some of all facets of delirium; cardiac arrhythmias including ventricular fibrillation and sudden death; hypocalcemia which is responsive only to Mg therapy; and hypokalemia which is not easily nor completely corrected without Mg therapy. The diversity of etiologies and the multiplicity of manifestations result in confusion and controversy. The documentation of normal renal function is absolutely necessary for maximum doses. The order of magnitude of dose is 1.0 meq Mg/kg on day 1, and 0.3 to 0.5 mEq/kg per day for 3 to 5 days. In emergencies such as convulsions or ventricular arrhythmias, a bolus injection of 1.0 gm (8.1 meq) of MgSO4 is indicated. Therapy of Mg deficiency in the presence of renal insufficiency requires smaller doses and frequent monitoring. Complete repletion occurs slowly.

Nutritional aspects of magnesium metabolism.

The absolute necessity for magnesium in plant and animal nutrition is easily appreciated when one realizes that magnesium is found in high concentration in cells. It is necessary for photosynthesis in plants and for all reactions involving adenosine triphosphate in plant and animal cells. Although it is abundant in nature in general, deficiencies occur in both plants and animals. Human beings need about 5 mg of magnesium per kg of body weight per day. Infants and young children need twice as much. Children and women during pregnancy or lactation require significantly greater amounts than normal adults. Various diseases result in a deficiency of magnesium because of interruption of food intake or intestinal or renal wasting of the mineral.