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Neonatal severe primary hyperparathyroidism(NSHPT; NHPT)

MedGen UID:
331326
Concept ID:
C1832615
Disease or Syndrome
Synonym: Neonatal severe hyperparathyroidism
SNOMED CT: Neonatal severe primary hyperparathyroidism (715218009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): CASR (3q13.33-21.1)
 
Monarch Initiative: MONDO:0009397
OMIM®: 239200
Orphanet: ORPHA417

Definition

Neonatal severe hyperparathyroidism usually manifests in the first 6 months of life with severe hypercalcemia, bone demineralization, and failure to thrive. Early diagnosis is critical because untreated NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy. Some infants have milder hyperparathyroidism and a substantially milder clinical presentation and natural history (summary by Egbuna and Brown, 2008). [from OMIM]

Clinical features

From HPO
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Hyperphosphaturia
MedGen UID:
78638
Concept ID:
C0268079
Disease or Syndrome
An increased excretion of phosphates in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Calcinosis
MedGen UID:
709
Concept ID:
C0006663
Finding
Formation of calcium deposits in any soft tissue.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hypercalcemia
MedGen UID:
5686
Concept ID:
C0020437
Disease or Syndrome
An abnormally increased calcium concentration in the blood.
Hypophosphatemia
MedGen UID:
39327
Concept ID:
C0085682
Disease or Syndrome
An abnormally decreased phosphate concentration in the blood.
Elevated circulating parathyroid hormone level
MedGen UID:
167805
Concept ID:
C0857973
Finding
An abnormal increased concentration of parathyroid hormone.
Primary hyperparathyroidism
MedGen UID:
66354
Concept ID:
C0221002
Disease or Syndrome
A type of hyperparathyroidism caused by a primary abnormality of the parathyroid glands (e.g., adenoma, carcinoma, hyperplasia). Primary hyperparathyroidism is associated with hyercalcemia.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeonatal severe primary hyperparathyroidism

Professional guidelines

PubMed

Eremkina A, Bibik E, Mirnaya S, Krupinova J, Gorbacheva A, Dobreva E, Mokrysheva N
Endocrine 2022 Sep;77(3):556-560. Epub 2022 Jul 12 doi: 10.1007/s12020-022-03127-3. PMID: 35821184
Cristina EV, Alberto F
Best Pract Res Clin Endocrinol Metab 2018 Dec;32(6):861-875. Epub 2018 Sep 28 doi: 10.1016/j.beem.2018.09.010. PMID: 30665551
Borg SA, Bishop NJ
Early Hum Dev 2018 Nov;126:32-37. Epub 2018 Sep 3 doi: 10.1016/j.earlhumdev.2018.08.014. PMID: 30190174

Recent clinical studies

Etiology

Marx SJ
Endocr Relat Cancer 2016 Jan;23(1):R1-14. Epub 2015 Sep 25 doi: 10.1530/ERC-15-0171. PMID: 26407873Free PMC Article
Wilhelm-Bals A, Parvex P, Magdelaine C, Girardin E
Pediatrics 2012 Mar;129(3):e812-6. Epub 2012 Feb 13 doi: 10.1542/peds.2011-0128. PMID: 22331334

Diagnosis

Cetani F, Dinoi E, Pierotti L, Pardi E
J Endocrinol Invest 2024 Sep;47(9):2157-2176. Epub 2024 Apr 18 doi: 10.1007/s40618-024-02366-7. PMID: 38635114
Marx SJ, Lourenço DM Jr
Horm Metab Res 2017 Nov;49(11):805-815. Epub 2017 Nov 14 doi: 10.1055/s-0043-120670. PMID: 29136674
Stokes VJ, Nielsen MF, Hannan FM, Thakker RV
J Bone Miner Res 2017 Nov;32(11):2157-2170. Epub 2017 Nov 2 doi: 10.1002/jbmr.3296. PMID: 28914984Free PMC Article
Varghese J, Rich T, Jimenez C
Endocr Pract 2011 Mar-Apr;17 Suppl 1:13-7. doi: 10.4158/EP10308.RA. PMID: 21478088
Toke J, Patócs A, Balogh K, Gergics P, Stenczer B, Rácz K, Tóth M
Wien Klin Wochenschr 2009;121(7-8):236-45. doi: 10.1007/s00508-009-1149-z. PMID: 19562279

Therapy

Koca SB
Turk J Pediatr 2023;65(5):853-861. doi: 10.24953/turkjped.2022.1040. PMID: 37853976
Capozza M, Chinellato I, Guarnieri V, Di Lorgi N, Accadia M, Traggiai C, Mattioli G, Di Mauro A, Laforgia N
BMC Pediatr 2018 Oct 30;18(1):340. doi: 10.1186/s12887-018-1319-0. PMID: 30376845Free PMC Article
Wilhelm-Bals A, Parvex P, Magdelaine C, Girardin E
Pediatrics 2012 Mar;129(3):e812-6. Epub 2012 Feb 13 doi: 10.1542/peds.2011-0128. PMID: 22331334

Prognosis

Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, Tollefsen S, Brown EM, Yang JJ, Thakker RV
Hum Mol Genet 2012 Jun 15;21(12):2768-78. Epub 2012 Mar 14 doi: 10.1093/hmg/dds105. PMID: 22422767
Wilhelm-Bals A, Parvex P, Magdelaine C, Girardin E
Pediatrics 2012 Mar;129(3):e812-6. Epub 2012 Feb 13 doi: 10.1542/peds.2011-0128. PMID: 22331334
Toke J, Patócs A, Balogh K, Gergics P, Stenczer B, Rácz K, Tóth M
Wien Klin Wochenschr 2009;121(7-8):236-45. doi: 10.1007/s00508-009-1149-z. PMID: 19562279
Steinmann B, Gnehm HE, Rao VH, Kind HP, Prader A
Helv Paediatr Acta 1984 May;39(2):171-86. PMID: 6543841

Clinical prediction guides

Koca SB
Turk J Pediatr 2023;65(5):853-861. doi: 10.24953/turkjped.2022.1040. PMID: 37853976
Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, Tollefsen S, Brown EM, Yang JJ, Thakker RV
Hum Mol Genet 2012 Jun 15;21(12):2768-78. Epub 2012 Mar 14 doi: 10.1093/hmg/dds105. PMID: 22422767
Thakker RV
Biochim Biophys Acta 1998 Dec 10;1448(2):166-70. doi: 10.1016/s0167-4889(98)00140-2. PMID: 9920407

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