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Disease Profile
Hypocalcemia, autosomal dominant
Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Unknown
Age of onset
All ages
ICD-10
E20.8
Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.
X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Not applicable
Categories
Congenital and Genetic Diseases; Endocrine Diseases; Nervous System Diseases
Summary
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 428
Definition
A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.
Epidemiology
Prevalence is unknown, but the disease is likely to be underdiagnosed as the hypocalcemia may remain asymptomatic.
Clinical expression and age of onset are extremely variable (depending on the degree of hypocalcemia), ranging from completely asymptomatic patients (in whom the diagnosis is made by chance during a routine exam) to patients with limited symptoms (cramps, asthenia, paresthesias) and patients with severe symptoms (i.e. recurrent seizures ). In addition to hypocalcemia, hypercalciuria or relative hypercalciuria (hypercalciuria within the normal range, but relatively high in the presence of hypocalcemia) is present. Hyperphosphatemia, hypomagnesemia and hypermagnesuria are also common. Nephrocalcinosis and impaired renal function have been reported and cases of AD hypocalcemia with classical features of Bartter syndrome (BS; see this term) have been described (referred to as BS with hypocalcemia; see this term). Serum levels of PTH are normal or low. In addition to regulation by PTH, environmental factors also influence calcium homeostasis and may explain why an initially well-controlled hypocalcemia may become symptomatic at various stages of life.
AD hypocalcemia is caused by activating mutations of the gene CASR (3q21.1), encoding the calcium-sensing receptor (CaSR). CaSR plays a key role in the regulation of calcium-phosphate metabolism by controlling PTH secretion and urinary calcium excretion in response to variations in serum calcium levels. Gain-of-function CASR mutations result in increased sensitivity of parathyroid and renal cells to calcium levels, leading to hypocalcemia being perceived as normal. Activating mutations in GNA11 (19p13.3) have also been described.
Diagnosis is made through analysis of calcium levels in the serum and urine and PTH levels, Molecular analysis of CaSR followed by GNA11 confirms diagnosis.
Differential diagnosis includes all other causes of hypoparathyroidism as well as BS in patients with renal salt wasting.
Antenatal diagnosis is possible.
Genetic counseling may be proposed but patients should be informed about the wide variability in clinical presentation.
Management and treatment
Treatment to normalize calcemia levels should be considered with caution, as any increase in calcium levels (even within the normal range) will be perceived by renal cells as hypercalcemia and lead to increased urinary calcium excretion, and possibly to nephrocalcinosis and renal failure. Treatment should aim towards finding a balance between the clinical signs of hypocalcemia and maintenance of calcium homeostasis, without being iatrogenic. Urine calcium levels should be monitored in order to avoid hypercalciuria rather than adapting treatment towards hypocalcemia. In asymptomatic and mildly symptomatic patients, treatment may not be necessary. Special care must be given to children as chronic hypocalcemia has deleterious effects on intellectual development. Treatment is based on administration of 1-alpha hydroxylated vitamin D (doses ranging from 0.5 to 1.5 micrograms/day in adults; higher doses are sometimes required in children). Careful monitoring of calciuria and regular kidney ultrasound are required. In cases where calcium homeostasis is difficult to achieve, exogenous PTH administered by infusion pump can be proposed.
The prognosis is variable, depending on the severity of the hypocalcemia and the possible consequences of inadequate treatment.
Visit the Orphanet disease page for more resources.
Symptoms
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
| Medical Terms | Other Names |
Learn More:
HPO ID
|
|---|---|---|
| 80%-99% of people have these symptoms | ||
| Anxiety |
Excessive, persistent worry and fear
|
0000739 |
| Cortical myoclonus | 0040148 | |
| Depressivity |
Depression
|
0000716 |
| EMG abnormality | 0003457 | |
| Emotional lability |
Emotional instability
|
0000712 |
| Fatigable weakness | 0003473 | |
| Hypercalciuria |
Elevated urine calcium levels
|
0002150 |
| Hypocalcemia |
Low blood calcium levels
|
0002901 |
| Paresthesia |
Pins and needles feeling
Tingling
[ more ] |
0003401 |
| Writer's cramp | 0002356 | |
| 30%-79% of people have these symptoms | ||
| Abdominal pain |
Pain in stomach
Stomach pain
[ more ] |
0002027 |
| Abnormal fingernail morphology |
Abnormal fingernails
Abnormality of the fingernails
[ more ] |
0001231 |
| Abnormal pattern of respiration |
Abnormal respiratory patterns
Unusual breathing patterns
[ more ] |
0002793 |
| Alopecia |
Hair loss
|
0001596 |
| Arrhythmia |
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] |
0011675 |
| Dry skin | 0000958 | |
| Hypermagnesiuria | 0012608 | |
| Hyperphosphatemia |
High blood phosphate levels
|
0002905 |
| Hypomagnesemia |
Low blood magnesium levels
|
0002917 |
| Hypotension |
Low blood pressure
|
0002615 |
| Nephrocalcinosis |
Too much calcium deposited in kidneys
|
0000121 |
| 5%-29% of people have these symptoms | ||
| Congestive heart failure |
Cardiac failure
Cardiac failures
Heart failure
[ more ] |
0001635 |
| Eczema | 0000964 | |
| Increased intracranial pressure |
Rise in pressure inside skull
|
0002516 |
| Irregular hyperpigmentation | 0007400 | |
| Optic atrophy | 0000648 | |
| Reduced bone mineral density |
Low solidness and mass of the bones
|
0004349 |
| Reduced consciousness/confusion |
Disturbances of consciousness
Lowered consciousness
[ more ] |
0004372 |
Diagnosis
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.
Testing Resources
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Learn more
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
Where to Start
- Genetics Home Reference (GHR) contains information on Hypocalcemia, autosomal dominant. This website is maintained by the National Library of Medicine.
In-Depth Information
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.