OBJECTIVE: To explore the clinical features and mutations of the TRPM6 gene in an infant featuring hypomagnesemia and secondary hypocalcemia. METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Targeted exome sequencing was carried out to screen the potential mutations. Suspected mutations were verified by Sanger sequencing. RESULTS: A novel homozygous c.5538delA (p.Q1846Qfs*2) mutation in the TRPM6 gene was identified in the proband, for which both of her parents were heterozygous carriers. CONCLUSION The homozygous frameshift mutation of TRPM6 gene (c.5538delA) probably underlies the disease in the proband. The finding has expanded the mutation spectrum of TRPM6 gene.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; Humans ; Hypocalcemia ; genetics ; Infant ; Magnesium Deficiency ; congenital ; genetics ; TRPM Cation Channels ; genetics

OBJECTIVE: To explore the molecular pathogenesis for a pedigree affected with hypocalcemia secondary to hypomagnesemia. METHODS: Sanger sequencing was used to detect potential variant of the TRPM6 gene in the patient and their parents. RESULTS: The results showed that the patient has carried novel homozygous c.3311C>T (p.Pro1104Leu) variant of the TRMP6 gene, for which both of his parents were heterozygous carriers. Analysis of protein functions using software predicted high risk of pathogenicity. CONCLUSION The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies the disease in this patient.
Heterozygote ; Humans ; Hypocalcemia ; genetics ; Magnesium ; Magnesium Deficiency ; genetics ; Male ; Pedigree ; TRPM Cation Channels ; genetics

BACKGROUND/AIMS: Magnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats. METHODS: Fifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks. RESULTS: Systolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats. CONCLUSIONS: Concurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.
Aldosterone/blood ; Angiotensin II/blood ; Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Animals ; Antihypertensive Agents/*pharmacology ; Biological Markers/blood ; Blood Pressure/*drug effects ; *Dietary Supplements ; Disease Models, Animal ; Hypertension/blood/*drug therapy/pathology/physiopathology ; Kidney/drug effects/pathology ; Magnesium/blood/*pharmacology ; Magnesium Deficiency/blood/*drug therapy/pathology/physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Systole ; Time Factors

OBJECTIVETo study the level of brain-derived neurotrophic factor (BDNF) in the microenvironment of the neuron-astrocyte co-culture system by Mg2+-free-induced seizure-like discharge and analyze the source of BDNF.

METHODSHippocampal neurons (N) of fetal rats and astrocytes (AST) of neonatal rats were purified and divided into four groups, included control N (Con N) group, Mg2+-free treated N (Mg2+-free N) group, control N+AST co-culture (Con N+AST) group and Mg2+-free treated N+AST co-culture (Mg2+-free N+AST) group. The Mg2+-free treated groups were exposed to Mg2+-free media for 3 hrs to induce a repeated spontaneous seizure-like discharge. The level of BDNF in each group at different time points was measured using ELISA.

RESULTSThe cellular morphous of AST changed in the Mg2+-free N+AST group at 48 hrs. Neuronal epileptiform activity was observed in the Mg2+-free media at 3 hrs, and continued to exist until the microenvironment returned to normal for 72 hrs. The BDNF level increased at 24 hrs and 48 hrs in the Con N+AST group compared with the control N group (P<0.05). Compared with Con N+AST group, BDNF level increased at 12, 24 and 48 hrs in the Mg2+-free N+AST group, especially at 12 and 24 hrs (P<0.01). There were no significant differences in the level of BDNF between the Con and Mg2+-free N groups. Compared with Mg2+-free N group, BDNF level increased at 24 hrs in the Mg2+-free N+AST group (P<0.05).

CONCLUSIONSThe results of the experiment suggest that BDNF in the Con N+AST group might be excreted from both N and AST, but chiefly from N. Activated AST may be the main source for increasing BDNF in the Mg2+-free N+AST group.

Animals ; Astrocytes ; chemistry ; Brain-Derived Neurotrophic Factor ; analysis ; Cellular Microenvironment ; Coculture Techniques ; Female ; Hippocampus ; chemistry ; Magnesium Deficiency ; metabolism ; Male ; Neurons ; chemistry ; Rats ; Rats, Wistar ; Seizures ; metabolism

Wilson's disease is an autosomal recessive disorder marked by disruptions in copper metabolism which leads to accumulation of copper in the liver, brain, cornea, and other tissues. Manifestations of this disease are more likely to be hepatic during early childhood and neurologic in adolescent. In addition, abnormalities that develop during disease progression may result in other manifestations such as hematologic, endocrine, or renal findings. Here we report a 13-year-old girl who presented with hypocalcemic tetany shortly after being diagnosed with Wilson's disease. Despite aggressive calcium, magnesium, and vitamin D replacement therapy, the hypocalcemia and hypomagnesemia did not promptly respond. Mineral levels in the blood took longer than 3 weeks to normalize. We speculate that a parathyroid insufficiency and disrupted vitamin D metabolism caused by copper accumulation and hepatic dysfunction resulted in hypocalcemic tetany.
Adolescent ; Brain ; Calcium ; Copper ; Cornea ; Disease Progression ; Hepatolenticular Degeneration ; Humans ; Hypocalcemia ; Hypoparathyroidism ; Liver ; Magnesium ; Tetany ; Vitamin D ; Vitamin D Deficiency

The link between diabetes mellitus and magnesium deficiency is well known. A growing body of evidence suggests that magnesium plays a pivotal role in reducing cardiovascular risks and may be involved in the pathogenesis of diabetes itself. While the benefits of oral magnesium supplementation on glycemic control have yet to be demonstrated in patients, magnesium supplementation has been shown to improve insulin sensitivity. Effects of Magnesium (Mg) supplementation on the glycemic control of 63 mild gestational diabetic patients were investigated. The use of an ionic, liquid minerals containing concentrated amounts of magnesium and chloride (CMD) was used for supplementation during the two week period and showed good glycemic control in the study group without additional need foe insulin injections.

Human ; Female ; Magnesium Deficiency ; Magnesium ; Insulin Resistance ; Ionic Liquids ; Cardiovascular Diseases ; Diabetes Mellitus ; Blood Glucose ; Pregnancy In Diabetics ; Insulin ; Minerals

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.
Vitamin K 2/chemistry/metabolism/*pharmacology ; Tomography, X-Ray Computed ; Tibia/pathology ; Rats ; Osteoporosis/*drug therapy/*prevention & control ; Male ; Magnesium Deficiency/diagnosis ; Magnesium/metabolism ; Homeostasis ; Female ; *Disease Models, Animal ; Diphosphonates ; Calcium/metabolism ; Bone and Bones/*drug effects/metabolism ; Bone Resorption ; Bone Diseases, Metabolic/*metabolism ; Animals

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.
Antihypertensive Agents ; Blood Pressure ; Calcium* ; Cations, Divalent ; Electrolytes ; Humans ; Hypertension ; Magnesium Deficiency ; Magnesium* ; Plasma* ; Potassium ; Renin* ; Sodium ; Urinalysis

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.
Antihypertensive Agents ; Blood Pressure ; Calcium* ; Cations, Divalent ; Electrolytes ; Humans ; Hypertension ; Magnesium Deficiency ; Magnesium* ; Plasma* ; Potassium ; Renin* ; Sodium ; Urinalysis

Primary hypomagnesemia is a rare inherited disorder and it is considered to be due to either a defect in the intestinal transport of magnesium or a defect in renal tubular transport. It is important to measure the urinary excretion of magnesium to differentiate the causes of magnesium deficiency. We report here an one-month-old female infant of primary hypomagnesemia who presented generalized tonic-clonic seizures. She had hypomagnesemia(<1.5mg/dL) and several seizure attacks but normal magnesium creatinine ratio in random urine and normal magnesium excretion in 24-hour urine. Continuous oral magnesium supplementation was necessary to avoid the recurrence of symptoms and maintain serum rnagnesium levels.
Creatinine ; Female ; Humans ; Infant ; Magnesium ; Magnesium Deficiency ; Recurrence ; Seizures