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Isolated autosomal dominant hypomagnesemia, Glaudemans type
Isolated autosomal dominant hypomagnesemia, Glaudemans type (IADHG) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by low serum magnesium (Mg) values but normal urinary Mg values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal.
ORPHA:199326Classification level: Disorder
- Synonym(s): -
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal dominant
- Age of onset: Infancy, Neonatal
- ICD-10: E83.4
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
IADHG has only been described in one large Brazilian kindred with 46 family members, of whom 21 were affected.
Onset of IADHG is typically in infancy. Clinical manifestations consist of recurrent and severe muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. Additional features include facial myokymia, arythmias, severe muscle spasms and muscular pain.
IADHG is caused by a N255D mutation in the KCNA1 gene (12p13), which encodes the voltage-gated potassium channel Kv1.1 (expressed in the kidney, where it colocalized with TRPM6 in apical membrane of distal convoluted tubule). Mutations in KCNA1 result in a nonfunctional channel protein, with a dominant negative effect on wild-type Kv1.1 channel function, which is involved in the maintenance of membrane voltage and optimal function of the TRPM6 channel.
Diagnosis relies on laboratory findings showing low serum Mg levels, while serum potassium (K) and calcium (Ca) levels and urinary Ca excretion are not affected. Diagnosis is confirmed by genetic screening of KCNA1.
Differential diagnosis includes the other forms of FPH and episodic ataxia type 1 (see these terms).
Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.
Management and treatment
Management is mainly symptomatic and involves a daily dose of magnesium chloride. During manifestations, intravenous or intramuscular administration of magnesium sulfate is preferred.
Prognosis highly depends on rapidity of diagnosis and treatment, as the disease can be fatal following tetany attacks.
- Summary information
- Polski (2014, pdf)