IllnessHypomagnesaemia, hereditary; differential diagnosis

NGS +

[Sanger]

Magnesium is essential for the proper functioning of numerous biological processes, such as the activity of hundreds of enzymes, the regulation of ion channels and the stabilization of negatively charged molecules such as DNA, RNA and ATP, etc. Clinically, Mg2+ deficiency can lead to weakness, fatigue, neuromuscular irritability, seizures and cardiac rhythm disturbances. Chronic hypomagnesemia may be associated with basal ganglia calcification, intellectual deficits, coma and death. With normal Mg2+ uptake, homeostasis is maintained primarily by regulated Mg2+ reabsorption in the loop of Henle and the distal contorted tubule of the kidney. Inadequate reabsorption leads to renal Mg2+ loss. Approximately 20 genes are involved in Mg2+ transport and the regulation of Mg2+ levels. The genetic hypomagnesemias are often divided into hypercalciuric, Gitelman-like, mitochondrial (including Kearns-Sayre syndrome) and other Mg2+ deficiencies, including intestinal. Apart from the rarer cases of mitochondrial/maternal transmission, the inheritance patterns of genetic hypomagnesemia are either autosomal recessive or autosomal dominant. The molecular genetic diagnosis depends critically on the prior clinical characterization of the patients and their families, respectively. Even with the use of an extensive gene panel, a negative DNA test result does not exclude the clinical diagnosis.

Reference: doi 10.1007/s00467-016-3416-3

• Allelic: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in (EGFR)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2DD (ATP1A)
• Allelic: Cystinosis, ocular nonnephropathic (CTNS)
• Allelic: Diabetes mellitus, noninsulin-dependent (HNF1B)
• Allelic: Enlarged vestibular aqueduct, digenic (KCNJ10)
• Allelic: Epilepsy idiopathic generalized, susceptibility to, 8 (CASR)
• Allelic: Episodic ataxia with myokymia/ Episodic ataxia type 1 (KCNA1)
• Allelic: Gracile bone dysplasia (FAM111A)
• Allelic: Hyperparathyroidism, neonatal (CASR)
• Allelic: Hypocalcemia, AD (CASR)
• Allelic: Hypocalciuric hypercalcemia, type I (CASR)
• Allelic: Kenny-Caffey syndrome, type 2 (FAM111A)
• Allelic: Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in (EGFR)
• Allelic: Nonsmall cell lung cancer, susceptibility to (EGFR)
• Allelic: Renal cell carcinoma (HNF1B)
• Allelic: Renal cysts and diabetes syndrome (HNF1B)
• Bartter syndrome, type 1, antenatal (SLC12A1)
• Bartter syndrome, type 2, antenatal (KCNJ1)
• Bartter syndrome, type 3 (CLCNKB)
• Bartter syndrome, type 4a (BSND)
• Bartter syndrome, type 4b, digenic (CLCNKB/CLCNKA)
• Congenital disorder of glycosylation, type IIn (SLC39A8)
• Cystinosis, atypical nephropathic (CTNS)
• Cystinosis, late-onset juvenile or adolescent nephropathic (CTNS)
• Cystinosis, nephropathic (CTNS)
• Gitelman syndrome [Potasium + magnesium depletion] (SLC12A3)
• Hyperphenylalaninemia, BH4-deficient, D (PCBD1)
• Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis (SARS2)
• Hypocalcemia, AD, with Bartter syndrome (CASR)
• Hypomagnesemia 1, intestinal (TRPM6)
• Hypomagnesemia 2, renal (FXYD2)
• Hypomagnesemia 3, renal (CLDN16)
• Hypomagnesemia 4, renal (EGF)
• Hypomagnesemia 5, renal, with ocular involvement (CLDN19)
• Hypomagnesemia 6, renal (CNNM2)
• Hypomagnesemia, seizures + mental retardation 2 (ATP1A)
• Myokymia 1 with/-out hypomagnesemia (KCNA1)
• SESAME syndrome (KCNJ10)
• Sensorineural deafness with mild renal dysfunction (BSND)