Primary hypomagnesemia with secondary hypocalcemia

Paunier, L; Radde, Ingeborg C.; Kooh, Sang Whay; Fraser, Donald R.

doi:10.1016/s0022-3476(65)81859-5

Cited by 87 publications

(79 citation statements)

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“…Children with this disease have seizures and tetany, secondary to extremely low Mg 2ϩ levels. 15,16 Their hypomagnesemia is due to a failure in the active transcellular (re)absorption of Mg 2ϩ from both the gut and the kidney. [17][18][19][20] A mutation in the transient receptor potential (TRP) channel transient receptor potential melastatin 6 (TRPM6) was found to be responsible for this disease.…”

Section: Intestinal Uptakementioning

confidence: 99%

Molecular Determinants of Magnesium Homeostasis

Alexander¹,

Hoenderop²,

Bindels³

2008

Journal of the American Society of Nephrology

135

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Section: Intestinal Uptakementioning

confidence: 99%

Molecular Determinants of Magnesium Homeostasis

Alexander¹,

Hoenderop²,

Bindels³

2008

Journal of the American Society of Nephrology

135

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“…P rimary hypomagnesemia with secondary hypocalcemia (HSH) was first described by Paunier et al (1). Patients usually present in early infancy with generalized convulsions or signs of increased neuromuscular excitability.…”

mentioning

confidence: 99%

Novel TRPM6 Mutations in 21 Families with Primary Hypomagnesemia and Secondary Hypocalcemia

Schlingmann

Sassen

Weber

et al. 2005

Journal of the American Society of Nephrology

159

173

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Primary hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder characterized by profound hypomagnesemia associated with hypocalcemia. Pathophysiology is related to impaired intestinal absorption of magnesium accompanied by renal magnesium wasting as a result of a reabsorption defect in the distal convoluted tubule. Recently, mutations in the TRPM6 gene coding for TRPM6, a member of the transient receptor potential (TRP) family of cation channels, were identified as the underlying genetic defect. Here, the results of a TRPM6 mutational analysis of 21 families with 28 affected individuals are presented. In this large patient cohort, a retrospective clinical evaluation based on a standardized questionnaire was also performed. Genotype analysis revealed TRPM6 mutations in 37 of 42 expected mutant alleles. Sixteen new TRPM6 mutations were identified, including stop mutations, frame-shift mutations, splice-site mutations, and deletions of exons. Electrophysiologic analysis of mutated ion channels after heterologous expression in Xenopus oocytes proved complete loss of function of TRPM6. Clinical evaluation revealed a homogeneous clinical picture at manifestation with onset in early infancy with generalized cerebral convulsions. Initial laboratory evaluation yielded extremely low serum magnesium levels, low serum calcium levels, and inadequately low parathyroid hormone levels. Treatment usually consisted of acute intravenous magnesium supplementation leading to relief of clinical symptoms and normocalcemia, followed by lifelong oral magnesium supplementation. Serum magnesium levels remained in the subnormal range despite adequate therapy. This is best explained by a disturbed magnesium conservation in the distal convoluted tubule, which emerged in all patients upon magnesium supplementation. Delay of diagnosis resulted in permanent neurologic damage in three patients.

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“…5-wk old male Sprague-Dawley rats weighing approximately 120 g were parathyroidectomized by electrocautery and fed chow containing 0.6%o calcium. 4 days later all animals with serum calcium less than 7.0 mg/100 ml were divided randomly into two groups and maintained on 1 Abbreviations used in this paper: 3',5'-AMP, adenosine 3',5'-monophosphate; 3',5'-GPM, guanosine 3',5'-monophosphate.…”

Section: Methodsmentioning

confidence: 99%

“…In magnesiumdepleted normal volunteers and individuals with familial hypomagnesemia, the hypocalcemia is often associated with mild elevations in serum phosphate. In all instances, serum calcium and phosphorus return to normal after treatment with magnesium supplements (1,2,7,8). Recently, it has been reported that individuals with severe hypomagnesemia secondary to chronic alcoholism (4) or steatorrhea (6) are resistant to the effects of parathyroid hormone.…”

Section: -676-05)mentioning

confidence: 98%