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Disease Profile

Neonatal severe hyperparathyroidism

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

Neonatal

ICD-10

E21.0

Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Categories

Congenital and Genetic Diseases; Endocrine Diseases; Musculoskeletal Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 417

Definition
Neonatal severe primary hyperparathyroidism (NSHPT) is characterized by severe hypercalcemia (> 3.5 mM) from birth and associated with major hyperparathyroidism.

Epidemiology
The prevalence is unknown.

Clinical description
The clinical manifestations are early (with onset occurring during the first days of life) and severe, including respiratory distress due to hypotonia and rib cage deformities, bone under mineralization, and multiple fractures, all of which influence the immediate vital prognosis.

Etiology
NSHPT is associated in most cases with homozygous inactivating mutations in the CASR gene, localized to 3q21.1. This gene encodes the calcium-sensing receptor (CaSR), a member of the subfamily of G protein-coupled transmembrane receptors. CaSR plays a key role in the regulation of phosphocalcic metabolism by controlling parathyroid hormone (PTH) secretion and calcium urinary excretion in response to variations in serum calcium levels.

Diagnostic methods
Biologically, children present with extremely high serum calcium and serum PTH levels and a relative hypocalciuria, but in some cases they present with a markedly elevated calciuria.

Differential diagnosis
'Familial hypocalciuric hypercalcemia (FHH; see this term) is a differential diagnosis. Hypercalcemia is usually milder and PTH levels are lower in FHH than in NSHPT and FHH is asymptomatic in most cases.'

Antenatal diagnosis
Prenatal diagnosis might be proposed to parents if they are both suffering from FHH.

Genetic counseling
NSHPT represents the homozygous form of FHH and is transmitted as an autosomal recessive trait. However, sporadic forms of NSHPT occur and are associated with a heterozygous de novo mutation in the CASR gene. To date, there have been no reports of severe neonatal hyperparathyroidism with homozygous mutations in those with FHH type 2 or 3 (see these terms) but their molecular identification is still too recent to make any definite conclusions.

Management and treatment
The control of hypercalcemia is often obtained through progressive therapeutic intervention involving the use of bisphosphonates, dialysis or even calcimimetics. If this is unsuccessful, a total parathyroidectomy is required. After parathyroidectomy, life-long treatment with 1-alpha hydoxylated vitamin D is required.

Prognosis
Patients can die from complications of hypercalcemia during the neonatal period from respiratory distress and dramatic hypercalcemia.

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
Abnormal calcium-phosphate regulating hormone level
0100530
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Abnormality of the thyroid gland
Thyroid abnormality
0000820
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Hepatomegaly
Enlarged liver
0002240
Muscular hypotonia
Low or weak muscle tone
0001252
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Short stature
Decreased body height
Small stature

[ more ]

0004322
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Anemia
Low number of red blood cells or hemoglobin
0001903
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Calcinosis
Calcium buildup in soft tissues of body
0003761
Constipation
0002019
Dyspnea
Trouble breathing
0002094
Elevated circulating parathyroid hormone level
0003165
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties in infancy
0008872
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypercalcemia
High blood calcium levels
Increased calcium in blood

[ more ]

0003072
Hypercalciuria
Elevated urine calcium levels
0002150
Hyperphosphaturia
High urine phosphate levels
0003109
Hypophosphatemia
Low blood phosphate level
0002148
Metaphyseal irregularity
Irregular wide portion of a long bone
0003025
Polydipsia
Extreme thirst
0001959
Polyuria
Increased urine output
0000103
Primary hyperparathyroidism
0008200
Tachypnea
Increased respiratory rate or depth of breathing
0002789

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.

Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

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 Neonatal severe hyperparathyroidism. 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.
  • Online Mendelian Inheritance in Man (OMIM) 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.