Rare Pulmonology News

Disease Profile

Familial hypocalciuric hypercalcemia

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.

Unknown

Age of onset

All ages

ageofonset-all.svg

ICD-10

E83.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

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

no.svg

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.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

Familial benign hypercalcemia; FBH; FBHH;

Summary

Familial hypocalciuric hypercalcemia (FHH) is an inherited disorder that causes abnormally high levels of calcium in the blood (hypercalcemia) and low to moderate levels of calcium in urine (hypocalciuric). People with FHH usually do not have any symptoms and are often diagnosed by chance during routine bloodwork. Weakness, fatigue, issues with concentration, and excessive thirst (polydipsia) have been reported by some people with FHH. Rarely, people with this disorder experience inflammation of the pancreas (pancreatitis) or a buildup of calcium in the joints (chondrocalcinosis).[1][2]

FHH is mainly classified into three different types depending on the genetic cause. FHH type 1 is the most common type of FHH and is caused by changes (also known as pathogenic variants or mutations) in the CASR gene. The protein made from the CaSR gene, the calcium-sensing receptor (CaSR protein), monitors and regulates the level of calcium in the blood. FHH type 2 is caused by changes in the GNA11 gene, and FHH type 3 is caused by changes in the AP2S1 gene. All three types of FHH are inherited in an autosomal dominant manner. In rare cases, FHH may be caused when a person's immune system mistakenly makes antibodies that attack the CaSR protein. The autoimmune form of FHH is not known to be caused by changes in a specific gene.[1][2][3]

Diagnosis of FHH is suspected by high levels of calcium in the blood, especially when there are no other symptoms present. Further blood and urine tests may be used to rule out other possible causes. Genetic testing can confirm the diagnosis of FHH, except in rare autoimmune cases.[2][4] Treatment is typically considered unnecessary because most people with FHH do not have symptoms. If pancreatitis occurs, removal of the parathyroid gland (parathyroidectomy) may be recommended.[1][2]

Symptoms

While most people with familial hypocalciuric hypercalcemia (FHH) do not have symptoms, associated symptoms may include:[1][2][3]

Rarely, adults with FHH may experience recurring inflammation of the pancreas (pancreatitis), a build-up of calcium crystals in certain joints of the body (chondrocalcinosis), and a build-up of calcium in the veins (vascular calcification).[1]

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
100% of people have these symptoms
Hypocalciuria
Low urine calcium levels
0003127
80%-99% of people have these symptoms
Parathormone-independent increased renal tubular calcium reabsorption
0003529
Reduced ratio of renal calcium clearance to creatinine clearance
Reduced ration of kidney calcium clearance to creatinine clearance
0003513
30%-79% of people have these symptoms
Infantile hypercalcemia
0008250
Osteomalacia
Softening of the bones
0002749
Renal hypophosphatemia
0008732
5%-29% of people have these symptoms
Chondrocalcinosis
Calcium deposits in joints
0000934
Episodic abdominal pain
0002574
Fatigue
Tired
Tiredness

[ more ]

0012378
Headache
Headaches
0002315
Hypermagnesemia
High blood magnesium levels
0002918
Hypomagnesiuria
Decreased urine magnesium
Low urine magnesium levels

[ more ]

0012609
Nausea and vomiting
0002017
Peptic ulcer
Sore in the lining of gastrointestinal tract
0004398
1%-4% of people have these symptoms
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Hypocalcemic seizures
Low calcium seizures
0002199
Lipoma
Fatty lump
Noncancerous fatty lump

[ more ]

0012032
Nephrolithiasis
Kidney stones
0000787
Pancreatitis
Pancreatic inflammation
0001733

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.

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.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Familial hypocalciuric hypercalcemia in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • !LINK! is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial hypocalciuric hypercalcemia. Click on the link to view a sample search on this topic.

References

  1. Lienhardt-Roussie A. Familial hypocalciuric hypercalcemia. Orphanet. May 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=405.
  2. Afzal M, Kathuria P. Familial Hypocalciuric Hypercalcemia (FHH). StatPearls [Internet]. StatPearls Publishing; January 2018; https://www.ncbi.nlm.nih.gov/books/NBK459190/.
  3. Stokes VJ, Nielsen MF, Hannan FM, Thakker RV. Hypercalcemic Disorders in Children. Journal of Bone and Mineral Research. November 2017; 32(11):2157-2170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703166/.
  4. Christensen SE1, Nissen PH, Vestergaard P, Mosekilde L. Familial hypocalciuric hypercalcaemia: a review. Curr Opin Endocrinol Diabetes Obes. December 18, 2011; 18(6):359-70. https://www.ncbi.nlm.nih.gov/pubmed/21986511.

Rare Pulmonology News