Course:MEDG550/Student Activities/Familial Hypocalciuric Hypercalcemia
Familial Hypocalciuric Hypercalcemia
Overview[1]
Familial hypocalciuric hypercalcemia (FHH) is a genetic condition that causes high levels of calcium in the blood throughout a person’s life.
Clinical Features[1][2][3]
Most people with FHH do not experience any symptoms.
Those who do show symptoms may experience the following:
- Tiredness that won’t go away even after resting (Fatigue)
- Weakness
- Headaches
- Having a difficult time passing stool (Constipation)
- Urinating frequently (Polyuria)
- Constant thirst (Polydipsia)
Though very rare, in severe cases people can develop additional health problems such as:
- Bones that are fragile and easily broken (Osteoporosis)
- Joint pain and stiffness (Arthritis, Chondrocalcinosis)
- Painful, hard clusters of crystal in the kidneys (Kidney stones, Nephrolithiasis)
- Abnormal heart rhythm (Arrhythmia)
- Inflammation of the pancreas (Pancreatitis)
Babies born with two altered copies of genes involved in FHH (see Genetics and Inheritance below) are at risk of:
- Overproduction of parathyroid hormone by the parathyroid gland at birth (Neonatal hyperparathyroidism)
- Easily broken bones
- Having difficulty growing and gaining weight (Failure to thrive)
Diagnosis[1][3]
Diagnosis of FHH involves both a blood and a urine test to look at calcium levels in the body. Genetic testing can also confirm a diagnosis.
Genetics
The human body is made up of millions of cells, and within each of those cells is DNA. This DNA is broken up into genes, which provide the instructions for how our bodies develop and function. Genes act as a blueprint to determine what features we have and how each aspect of our body works, similar to how a recipe provides the instructions on how to bake a cake. Most people have two copies of each gene, one copy from each parent.
There is lots of variation between people when it comes to the specific set of instructions that we have, and this variety is what makes everyone different and each person unique. This variation comes from changes to the genetic code. The genetic code can be thought of as the steps in the recipe that determine what each gene does. Some changes don’t cause any health problems or don’t have a known effect, whereas other changes can be responsible for a disease. This can be compared to adding yogurt to your cake batter instead of sour cream, it won’t make any difference to the outcome of your cake, whereas if you added a cup of salt instead of a cup of sugar, the difference will be much more noticeable.
A disorder is considered genetic when an individual has an altered gene that increases their risk of developing a particular condition. This altered gene can be inherited from a parent, or be unique to the person who has it.
Inheritance[1]
FHH is what is called an autosomal dominant condition. This means that only one copy of the altered gene is enough to cause the signs and symptoms of FHH.
People with FHH will pass on one of their copies of a gene involved in FHH to each of their children. Each child has a 50% or 1/2 chance of inheriting the altered copy and a 50% chance of inheriting the unaltered copy. Therefore, each child of someone with FHH will have a 50% or 1/2 chance of also having FHH.
Genes Involved[2][4]
There are three genes involved in FHH.
CASR: Changes in the CASR gene (also known as the calcium-sensing receptor gene) can cause FHH type I by affecting how well the body reacts to calcium, and how it keeps those levels in a normal range. This is the most common type of FHH, as 65% of people with FHH have changes in this gene.
GNA11: Changes in the GNA11 gene can cause FHH type II.
AP2S1: Changes in the AP2S1 gene can cause FHH type III. People with disease-causing changes in this gene tend to have more symptoms of FHH than people with changes in the other two genes.
Prevalence[1]
It is estimated that between 1 in 10,000 and 1 in 100,000 people have FHH, but there are probably many more people with this condition who don’t get diagnosed because they don’t show any signs of having a disease.
Non-Genetic Causes[1]
Rarely, FHH can be caused by the body attacking itself. This happens when the defence systems in the body that are designed to protect against germs and other things that can harm us can’t tell the difference between those harmful things and the body’s own cells.
Treatment and Management[1][2][3]
Since very few people with FHH experience any symptoms, there are no recommended treatments for the condition. For most people, there are no long term health implications of having this condition.
In people who do experience symptoms or additional health problems, certain medications may be used but they are not designed for treatment of FHH and it would be up to a doctor to decide whether or not those medications are right for their patient. In rare cases, people may have their parathyroid removed.
Genetic Counselling[3][5]
Because FHH is a genetic condition, many members of the same family can have the condition. It may be helpful for families to see a genetic counsellor to confirm whether they have FHH or a different health problem that is causing high calcium levels in their blood, since these other health problems might have more severe symptoms or other impacts to a person's health. Genetic testing for FHH can help to rule out these other potential causes of high calcium levels in the blood.
Genetic counsellors are healthcare professionals specialized in genetics and counselling. They can:
- Assess the likelihood that someone has a genetic condition and the chances that they could pass it on to their children
- Offer genetic testing to diagnose a genetic conditions (often with a simple blood or cheek swab test)
- Provide information about genetic conditions and how they can be managed
While genetic counsellors provide information on the physical aspects and medical implications of genetic conditions, they also focus on the potential social and emotional impacts of genetic testing and diagnoses. Genetic information can be confusing and overwhelming to hear. Genetic counsellors are there to break down the information to make it easy to understand and are there to support each patient in making the choices that work best for them and their family by providing a space for patients to voice their concerns and ask questions.
References
- ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Suarez, Corina; Anastasopoulou, Catherine; Kathuria, Pranay (July 2, 2024). "Familial Hypocalciuric Hypercalcemia". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Retrieved January 30, 2025.
- ↑ Jump up to: 2.0 2.1 2.2 Huzmeli, Can (August 2024). "An Overview of Familial Hypocalciuric Hypercalcemia". Journal of Clinical Nephrology. 8(2): 114–117 – via HSPI.
- ↑ Jump up to: 3.0 3.1 3.2 3.3 Christensen, Signe; Nissen, Peter; Vestergaard, Peter; Mosekilde, Leif (December 2011). "Familial hypocalciuric hypercalcaemia: a review". Current Opinion in Endocrinology, Diabetes and Obesity. 18(6): 359–370 – via Lippincott.
- ↑ Vargas-Poussou, Rosa; et al. (May 2016). "Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences". The Journal of Clinical Endocrinology and Metabolism. 101(5): 2185–2195 – via Oxford Academic. Explicit use of et al. in:
|first=(help) - ↑ Lee, Janet; Shoback, Dolores (October 2018). "Familial hypocalciuric hypercalcemia and related disorders". Best Practice & Research Clinical Endocrinology & Metabolism. 32(5): 609–619 – via PMC.