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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Endocrinology · Familial Hypocalciuric Hypercalcemia

What's the Difference Between FHH Type 1, 2, and 3?

At a Glance

FHH Type 1, 2, and 3 are genetic conditions that cause high blood calcium. Types 1 and 2 are usually mild and symptom-free, while Type 3 is more pronounced and can cause higher calcium levels and lower bone density. All types are typically managed with careful observation rather than surgery.

In this answer

3 sections

01

The Genetics: What Causes the Different Types?

02

Differences in Symptoms and Severity

03

How Are the Types Managed?

If your test results say you have Familial Hypocalciuric Hypercalcemia Type 1 (FHH1), you might naturally wonder if there are other types—and whether “Type 1” means you have the most severe form. The short answer is that Type 1 is not the worst kind of FHH; it is simply the most common [1].

There are three known types of FHH: Type 1, Type 2, and Type 3 [1]. The primary difference between them comes down to which specific gene is causing the condition [2]. While they all affect how your body senses and manages calcium, they have slightly different traits. Importantly, all three types are generally managed with observation rather than surgery [3][4].

The Genetics: What Causes the Different Types?

Your body relies on a delicate system to monitor calcium levels in your blood. In FHH, a genetic change (mutation) acts like a faulty thermostat, causing your body to maintain calcium at a slightly higher “normal” baseline [3].

Because FHH is an inherited condition (“familial”), these gene mutations are passed down through families. It follows an autosomal dominant inheritance pattern, meaning that if you have FHH, each of your children has a 50% chance of inheriting the gene [5]. The type of FHH you have depends on which part of the “thermostat” is affected:

  • FHH Type 1 (FHH1): This is caused by a mutation in the CASR gene [1][2]. The CASR gene directly creates the calcium-sensing receptor, which is the sensor that detects calcium in your blood. FHH1 is the most common form of the condition [6].
  • FHH Type 2 (FHH2): This type is caused by a mutation in the GNA11 gene [1][2]. This gene produces a protein that helps the calcium-sensing receptor send its signals.
  • FHH Type 3 (FHH3): This is caused by a mutation in the AP2S1 gene [1][2]. This gene helps regulate how the calcium-sensing receptor functions and is recycled by the cell [6].

Differences in Symptoms and Severity

For the vast majority of people, FHH1 and FHH2 are asymptomatic, meaning they do not cause noticeable symptoms or health problems [7]. Patients usually discover they have FHH by accident during routine blood work.

However, FHH3 is generally considered to be the most pronounced or “severe” of the three types [8][9]. While FHH1 and FHH2 are typically mild, FHH3 can sometimes feature:

  • Higher calcium levels: People with FHH3 tend to have higher levels of calcium in their blood compared to those with FHH1 or FHH2 [8][9].
  • Lower bone density: FHH3 is more frequently associated with lowered bone mineral density [8].
  • Cognitive and learning differences: Unlike Types 1 and 2, FHH3 is sometimes linked to neurodevelopmental traits. This can include mild learning difficulties, hyperactivity, speech delays, or traits associated with autism spectrum disorder [10][11][7]. This occurs because the AP2S1 gene is also involved in the early development of the nervous system [12].

How Are the Types Managed?

The management approach for all three types is fundamentally similar: careful observation [3]. Because FHH is usually a benign (harmless) condition, distinguishing it from other calcium disorders—specifically primary hyperparathyroidism (PHPT)—is critical. Accurate diagnosis ensures that FHH patients avoid unnecessary parathyroid surgeries, which do not cure FHH and provide no long-term benefits [3][4][13].

In standard cases of FHH1 and FHH2, no medication or treatment is needed [7]. “Observation” usually just means periodic routine blood tests to ensure your calcium levels remain stable, at a frequency guided by your doctor [14].

Because FHH3 can sometimes result in much higher calcium levels or problematic symptoms, these patients are occasionally treated with a medication called a calcimimetic (like cinacalcet) [7][15][16]. Calcimimetics help trick the calcium-sensing receptor into thinking there is more calcium in the blood, prompting the body to lower its calcium levels [11][17].

Regardless of which type of FHH you have, continuing to monitor your calcium levels and working with an endocrinologist is the best step forward. Knowing your specific genetic type helps your doctor personalize your long-term monitoring plan.

Common questions in this guide

What causes the different types of FHH?
The three types of FHH are caused by mutations in different genes that help regulate your body's calcium levels. Type 1 involves the CASR gene, Type 2 involves the GNA11 gene, and Type 3 involves the AP2S1 gene.
Is FHH Type 1 the most severe kind?
No, FHH Type 1 is the most common form and typically causes no symptoms. FHH Type 3 is generally considered the most pronounced or severe form of the condition, often featuring higher blood calcium levels.
Can FHH be treated with parathyroid surgery?
No, parathyroid surgery does not cure familial hypocalciuric hypercalcemia and provides no long-term benefits. Accurately diagnosing FHH is crucial to help patients avoid unnecessary surgical procedures.
How is FHH managed?
For most people with FHH Type 1 and Type 2, the condition is managed with simple observation and routine blood tests. In some cases of FHH Type 3 where calcium levels are very high, medications called calcimimetics may be prescribed.
How is FHH inherited?
FHH is passed down through families in an autosomal dominant pattern. This means that if you have the genetic mutation for FHH, each of your children has a 50% chance of inheriting it.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How often should I have my blood calcium levels and bone mineral density checked?
  2. 2.Should my immediate family members, like siblings or children, get genetic testing for my specific FHH mutation?
  3. 3.Are my current calcium levels typical for my specific type of FHH, or are they higher than expected?
  4. 4.Would any specific dietary changes regarding calcium or vitamin D intake be beneficial or harmful for me?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

Can Water Pills or Lithium Affect FHH Urine Tests?High Calcium: How Do Doctors Tell FHH1 From Cancer?How Does Vitamin D Deficiency Affect FHH1 Testing?Does My Baby Need Calcium Monitoring if I Have FHH1?High Calcium After Parathyroid Surgery: Could It Be FHH1?What Are the Long-Term Complications of FHH1?What is Neonatal Severe Hyperparathyroidism (NSHPT)?What Medications Are Used to Treat High Calcium in FHH1?

References

References (17)
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    Congenital primary hyperparathyroidism.

    Marini F, Giusti F, Brandi ML

    Best practice & research. Clinical endocrinology & metabolism 2025; (39(2)):101982 doi:10.1016/j.beem.2025.101982.

    PMID: 39939267
  2. 2

    AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia.

    Hovden S, Rejnmark L, Ladefoged SA, Nissen PH

    European journal of endocrinology 2017; (176(2)):177-185 doi:10.1530/EJE-16-0842.

    PMID: 27913609
  3. 3

    A novel homozygous mutation of the calcium-sensing receptor gene associated with apparent autosomal recessive inheritance of familial hypocalciuric hypercalcemia.

    Li N, Li X, Ni XL, et al.

    Chinese medical journal 2021; (134(15)):1869-1871 doi:10.1097/CM9.0000000000001568.

    PMID: 34397587
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    Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports.

    Courtney A, Hill A, Smith D, Agha A

    BMC endocrine disorders 2022; (22(1)):324 doi:10.1186/s12902-022-01231-z.

    PMID: 36536367
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    A novel homozygous c.301T > C, p.Y101H variant in the GNA11 gene is implicated in familial hypocalciuric hypercalcemia type 2 in a proband with the heterozygous variant present in mother and father - A case report.

    Koca SB, Balta B

    Scandinavian journal of clinical and laboratory investigation 2025; (85(8)):670-674 doi:10.1080/00365513.2025.2588772.

    PMID: 41240382
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    [Disorders Caused by Mutations in Calcium-Sensing Receptor and Related Diseases.]

    Michigami T

    Clinical calcium 2017; (27(4)):521-527.

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    Familial hypocalciuric hypercalcemia in an infant: diagnosis and management quandaries.

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    Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis.

    Hannan FM, Babinsky VN, Thakker RV

    Journal of molecular endocrinology 2016; (57(3)):R127-42 doi:10.1530/JME-16-0124.

    PMID: 27647839
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    Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.

    Vargas-Poussou R, Mansour-Hendili L, Baron S, et al.

    The Journal of clinical endocrinology and metabolism 2016; (101(5)):2185-95 doi:10.1210/jc.2015-3442.

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    Neurodevelopmental Abnormalities in Patients with Familial Hypocalciuric Hypercalcemia Type 3.

    Chinoy A, Nicholson J, Skae M, et al.

    The Journal of pediatrics 2023; (257()):113367 doi:10.1016/j.jpeds.2023.02.013.

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    Cinacalcet therapy in symptomatic 11-year-old girl with familial hypocalciuric hypercalcemia type 3.

    Kołbuc M, Beck BB, Bukowska-Olech E, et al.

    Pediatric nephrology (Berlin, Germany) 2026; (41(6)):1637-1640 doi:10.1007/s00467-025-07135-z.

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    N-ethyl-N-nitrosourea-Induced Adaptor Protein 2 Sigma Subunit 1 (Ap2s1) Mutations Establish Ap2s1 Loss-of-Function Mice.

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    Novel mutations of the calcium-sensing receptor impede differential diagnosis of primary hyperparathyroidism and familial hypocalciuric hypercalcemia.

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This page explains the genetic differences between FHH types for educational purposes only. Always consult your endocrinologist or genetic counselor to interpret your specific genetic test results and determine your optimal monitoring plan.

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