What is Neonatal Severe Hyperparathyroidism (NSHPT)?
At a Glance
Neonatal Severe Hyperparathyroidism (NSHPT) is a rare, life-threatening condition that happens if a baby inherits two mutated CASR genes—one from each parent with FHH1. Parents with FHH1 should have their partners genetically tested before pregnancy to assess the risk of NSHPT.
In this answer
4 sections
If you and your partner both carry the gene mutation that causes Familial Hypocalciuric Hypercalcemia Type 1 (FHH1), your child is at risk of being born with a rare, life-threatening condition called Neonatal Severe Hyperparathyroidism (NSHPT) [1][2]. While FHH1 itself is generally mild and asymptomatic because it involves a single mutated gene, NSHPT occurs when a baby inherits two mutated genes — one from each parent [3][4].
Because FHH1 is a rare condition, the chances of an unrelated partner also having the mutation are exceptionally low. However, because of the severe risks associated with NSHPT, it is highly recommended that your partner undergo genetic testing before you try to conceive [5][2].
How the Genetics Work
FHH1 is caused by a mutation in the CASR gene, which provides instructions for making the calcium-sensing receptor [6][7]. This receptor acts like a thermostat for calcium in your blood.
- One Mutated Gene (FHH1): When a person has one normal CASR gene and one mutated CASR gene, their “thermostat” is set a bit too high. This results in FHH1, meaning they have slightly elevated calcium levels but usually no symptoms [8][9].
- Two Mutated Genes (NSHPT): If both you and your partner have FHH1, each of you has a 50% chance of passing the mutated gene to your child. This means there is a 25% chance with each pregnancy that the baby will inherit two mutated genes [1]. With two severely mutated copies of the CASR gene that do not function properly, the baby’s calcium “thermostat” is essentially broken [8].
Symptoms and Risks of NSHPT
In a baby born with NSHPT, the body struggles to sense calcium in the blood [9]. As a result, the parathyroid glands (tiny glands in the neck that control calcium) go into overdrive, producing massive amounts of parathyroid hormone (PTH) [3].
This floods the infant’s bloodstream with dangerously high levels of calcium, a state known as a hypercalcemic crisis [3][10]. NSHPT typically presents in the first few weeks of life and can cause:
- Failure to thrive and poor feeding [3][11]
- Severe bone weakness and demineralization (which can lead to rib fractures) [12][13]
- Severe respiratory distress (trouble breathing) [11]
- Neurological issues, including developmental delays or seizures [11][3]
Without immediate medical intervention, NSHPT is life-threatening [3].
How is NSHPT Treated?
If a baby is born with NSHPT, immediate and aggressive treatment is required in the Neonatal Intensive Care Unit (NICU).
- Medication: Doctors will often first use calcimimetics, such as cinacalcet, which are drugs that help “trick” the mutated receptors into sensing calcium and lowering PTH levels [14][15]. This can stabilize the baby and act as a bridge to surgery [4].
- Surgery: In most cases, medications are not enough, and the baby will require a total parathyroidectomy [16][17]. This is a life-saving surgery to completely remove the overactive parathyroid glands [18][19]. After this surgery, the child will need lifelong calcium and vitamin D supplementation, typically given as daily liquid drops in infancy.
Next Steps for Family Planning
The risk of passing on NSHPT can be managed and mitigated through careful family planning [5][2].
- Partner Testing: Your partner should have genetic testing to see if they carry a CASR mutation [20]. Because FHH1 often has no symptoms, a genetic test is the only definitive way to know their carrier status. If they are not a carrier, the risk of NSHPT is virtually zero (though your child still has a 50% chance of inheriting your FHH1).
- Genetic Counseling: Meet with a genetic counselor who specializes in endocrine disorders. They can review your family history and help you understand your specific risks [20][12]. They can also help you navigate the financial and logistical realities of genetic testing and reproductive options.
- Explore Reproductive Options: If both you and your partner are carriers, you might consider natural conception combined with close fetal monitoring, or using In Vitro Fertilization (IVF) with Preimplantation Genetic Testing (PGT-M) to ensure only embryos without the double mutation are implanted.
What if you are already pregnant?
If you are already pregnant and haven’t had partner testing, there is no need to panic. The chances of an unrelated partner having FHH1 remain very low. Contact your healthcare team so they can arrange genetic testing for your partner if needed. If both of you are confirmed carriers, a specialized multidisciplinary team (including maternal-fetal medicine specialists and neonatologists) will closely monitor your pregnancy and be prepared to test and care for your baby immediately at birth [20].
Common questions in this guide
How does a baby get Neonatal Severe Hyperparathyroidism (NSHPT)?
What are the symptoms of NSHPT in a newborn?
How is NSHPT treated in infants?
Should my partner get genetic testing if I have FHH?
Questions to Ask Your Doctor
Curated prompts to bring to your next appointment.
- 1.Because I have an FHH1 diagnosis, how can we facilitate genetic testing for my partner to definitively check their carrier status?
- 2.If my partner does carry an FHH-causing mutation, can you refer us to a specialized reproductive endocrinologist or genetic counselor who has experience with this specific condition?
- 3.What does maternal and fetal monitoring look like during pregnancy if there is a known risk for NSHPT?
- 4.Will insurance typically cover genetic counseling, and potentially IVF with PGT-M, given the severe medical risks of NSHPT?
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References
References (20)
- 1
Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy: A case report and literature review.
Sun X, Huang L, Wu J, et al.
Medicine 2018; (97(45)):e13128 doi:10.1097/MD.0000000000013128.
PMID: 30407334 - 2
Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia.
Murphy H, Patrick J, Báez-Irizarry E, et al.
European journal of medical genetics 2016; (59(4)):227-31.
PMID: 26855056 - 3
A Case of Neonatal Severe Hyperparathyroidism: Challenges in Management.
Gupta P, Tak SA, S AV, et al.
Indian journal of pediatrics 2022; (89(10)):1025-1027 doi:10.1007/s12098-022-04169-1.
PMID: 35380381 - 4
A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug.
Leunbach TL, Hansen AT, Madsen M, et al.
Bone reports 2021; (14()):100761 doi:10.1016/j.bonr.2021.100761.
PMID: 33748353 - 5
Case Report: Familial hypocalciuric hypercalcemia type 1 with a novel mutation combined with Gitelman syndrome and a review of the literature.
He T, Li X, Li G, et al.
Frontiers in endocrinology 2025; (16()):1503128 doi:10.3389/fendo.2025.1503128.
PMID: 40070587 - 6
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 - 7
Rare diseases caused by abnormal calcium sensing and signalling.
Tőke J, Czirják G, Enyedi P, Tóth M
Endocrine 2021; (71(3)):611-617 doi:10.1007/s12020-021-02620-5.
PMID: 33528764 - 8
Reduced affinity of calcium sensing-receptor heterodimers and reduced mutant homodimer trafficking combine to impair function in a model of familial hypocalciuric hypercalcemia type 1.
Wang X, Lundblad J, Smith SM
PloS one 2022; (17(7)):e0266993 doi:10.1371/journal.pone.0266993.
PMID: 35857775 - 9
Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca2+ Sensing but Not G Protein Interaction.
Goolam MA, Brown AP, Edwards KT, et al.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2022; (37(9)):1787-1807 doi:10.1002/jbmr.4651.
PMID: 35848051 - 10
Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.
Capozza M, Chinellato I, Guarnieri V, et al.
BMC pediatrics 2018; (18(1)):340 doi:10.1186/s12887-018-1319-0.
PMID: 30376845 - 11
Ten-year follow-up report and neurologic sequelae in a case of neonatal severe primary hyperparathyroidism.
Khosroshahi N, Haghshenas Z, Afrooghe A, et al.
Clinical case reports 2023; (11(7)):e7626 doi:10.1002/ccr3.7626.
PMID: 37492070 - 12
[Clinical characteristics and genetic analysis of two children with neonatal severe hyperparathyroidism].
Xun Z, Wang Z, Du Y, Liu C
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2023; (40(8)):979-985 doi:10.3760/cma.j.cn511374-20220726-00492.
PMID: 37532498 - 13
Severe Hyperparathyroidism in a 3-year-old girl Due to Homozygous Inactivating Variant of the Calcium Sensing Receptor Gene.
Boddu SK, Mehrotra RN, Chakravarthy S
JCEM case reports 2025; (3(5)):luaf057 doi:10.1210/jcemcr/luaf057.
PMID: 40162299 - 14
Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature.
Forman TE, Niemi AK, Prahalad P, et al.
Journal of pediatric endocrinology & metabolism : JPEM 2019; (32(3)):305-310 doi:10.1515/jpem-2018-0307.
PMID: 30730839 - 15
Cinacalcet as a First-Line Treatment in Neonatal Severe Hyperparathyroidism Secondary to Calcium Sensing Receptor (CaSR) Mutation.
Gulcan-Kersin S, Kirkgoz T, Eltan M, et al.
Hormone research in paediatrics 2020; (93(5)):313-321 doi:10.1159/000510623.
PMID: 33147586 - 16
Neonatal Severe Hyperparathyroidism: Anaesthetic Considerations for Removal of Pea-size Glands in Children.
Parmar U, Dias R, P G, Bamnote M
Turkish journal of anaesthesiology and reanimation 2025; (53(3)):132-135 doi:10.4274/TJAR.2025.241409.
PMID: 40150828 - 17
Management of Neonatal Severe Hyperparathyroidism due to Homozygous CASR Mutation: Challenges and Literature Insights.
Karakaş H, Aksakal N, Tarçın G, et al.
Molecular syndromology 2025; (16(6)):606-614 doi:10.1159/000543911.
PMID: 41378239 - 18
Successful parathyroidectomy with intra-operative parathyroid hormone monitoring in a neonate with severe primary hyperparathyroidism caused by homozygous mutation in CASR gene.
Sorapipatcharoen K, Mahachoklertwattana P, Tim-Aroon T, et al.
Journal of paediatrics and child health 2020; (56(7)):1144-1146 doi:10.1111/jpc.14757.
PMID: 31883284 - 19
Neonatal severe hyperparathyroidism: A case report.
Shaukat M, Ahmad HM, Shafiq MU
JPMA. The Journal of the Pakistan Medical Association 2022; (72(12)):2538-2541 doi:10.47391/JPMA.4195.
PMID: 37246686 - 20
Prenatal features and neonatal management of severe hyperparathyroidism caused by the heterozygous inactivating calcium-sensing receptor variant, Arg185Gln: A case report and review of the literature.
Aubert-Mucca M, Dubucs C, Groussolles M, et al.
Bone reports 2021; (15()):101097 doi:10.1016/j.bonr.2021.101097.
PMID: 34169121
This page provides educational information about NSHPT and FHH genetics. It does not replace professional medical advice. Always consult a genetic counselor or maternal-fetal medicine specialist regarding your family planning risks.
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