What are the other Names for this Condition? (Also known as/Synonyms)

• Hypomagnesemia caused by Selective Magnesium Malabsorption
• Hypomagnesemic Tetany
• Intestinal Hypomagnesemia with Secondary Hypocalcemia

What is Primary Hypomagnesemia with Secondary Hypocalcemia? (Definition/Background Information)

• Primary Hypomagnesemia with Secondary Hypocalcemia (PHSH) is a disease characterized by very low magnesium levels in the blood
• The disease begins during the first months of life with generalized and recurrent seizures which do not improve with usual treatment
• Additional features include tetany (spasms of the hands and feet, cramps, spasm of the voice box (larynx), and overactive neurological reflexes), failure to thrive, restlessness, tremors, muscle spasms, and bluish skin around the mouth (perioral cyanosis)
• Abnormal heart rhythm (cardiac arrhythmia) may be observed. The low levels of magnesium result in low levels of parathyroid hormone (PTH) and in low levels of calcium in the bloods (hypocalcemia)
• Primary Hypomagnesemia with Secondary Hypocalcemia is caused by mutations in the TRPM6 gene. Inheritance is autosomal recessive
• Untreated, the disease may be fatal or lead to severe neurologic damage. The treatment of Primary Hypomagnesemia with Secondary Hypocalcemia involves giving magnesium, usually in the vein (intravenously), followed by life-long high-dose oral magnesium

(Source: Primary Hypomagnesemia with Secondary Hypocalcemia; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Primary Hypomagnesemia with Secondary Hypocalcemia? (Age and Sex Distribution)

• Primary Hypomagnesemia with Secondary Hypocalcemia is a rare congenital condition, with just about 100 cases reported in the literature
• The onset of symptoms may occur at birth
• Both genders are equally affected by this disorder
• Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for Primary Hypomagnesemia with Secondary Hypocalcemia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Primary Hypomagnesemia with Secondary Hypocalcemia can be inherited
• Additionally, being a child of consanguineous parents is a risk factor for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Primary Hypomagnesemia with Secondary Hypocalcemia? (Etiology)

• Primary Hypomagnesemia with Secondary Hypocalcemia is caused by mutation(s) in the TRPM6 gene
• This gene codes for the protein known as “transient receptor potential cation channel subfamily M, member 6”. This protein acts as a ion channel, allowing magnesium, and possibly calcium, to gain entry into cells
• This protein is present in the epithelial cells of the large intestine, and plays a crucial role in the absorption of magnesium in the intestines
• When this gene is mutated, a deficiency of TRPM6 protein prevents magnesium absorption in the intestines, leading to the characteristic signs and symptoms of this disorder

What are the Signs and Symptoms of Primary Hypomagnesemia with Secondary Hypocalcemia?

The signs and symptoms of Primary Hypomagnesemia with Secondary Hypocalcemia may include:

• Failure to thrive
• Restlessness
• Hypocalcemia
• Hypomagnesemia
• Seizures
• Tetany (intermittent muscle spasms)
• Tremors
• Bluish skin around the mouth

(Source: Primary Hypomagnesemia with Secondary Hypocalcemia; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Primary Hypomagnesemia with Secondary Hypocalcemia Diagnosed?

Primary Hypomagnesemia with Secondary Hypocalcemia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests to check for levels if magnesium and calcium in the blood and urine. Renal magnesium levels may be tested following an intravenous magnesium load
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Primary Hypomagnesemia with Secondary Hypocalcemia?

The complications of Primary Hypomagnesemia with Secondary Hypocalcemia may include:

• Chronic convulsive disorder
• Seizures that are unresponsive to anti-seizure medications
• Mental retardation
• Abnormal heart rhythms

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Primary Hypomagnesemia with Secondary Hypocalcemia Treated?

There is no cure for Primary Hypomagnesemia with Secondary Hypocalcemia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. Treatment methods may include:

• Intravenous or intramuscular magnesium administration when symptoms are present
• Lifelong oral administration of high doses of magnesium
• Parenteral magnesium, if required

How can Primary Hypomagnesemia with Secondary Hypocalcemia be Prevented?

Primary Hypomagnesemia with Secondary Hypocalcemia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Primary Hypomagnesemia with Secondary Hypocalcemia? (Outcomes/Resolutions)

• The prognosis of Primary Hypomagnesemia with Secondary Hypocalcemia is dependent upon an early diagnosis and prompt treatment 
• A delayed diagnosis and consequently delayed treatment can result in chronic convulsive disorder and life-threatening and irreversible neurological complications
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Primary Hypomagnesemia with Secondary Hypocalcemia:

Primary Hypomagnesemia with Secondary Hypocalcemia may also be known by the following synonyms:

• HOMG1
• HSH
• Hypomagnesemia Intestinal Type 1
• PHSH (Primary Hypomagnesemia with Secondary Hypocalcemia)

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/