pseudohypoparathyroidism

Types include:

;Type 1a (OMIM {{OMIM|103580||none}})

: Has a characteristic phenotypic appearance (Albright's hereditary osteodystrophy), including short fourth and fifth metacarpals and a rounded facies. It is most likely an autosomal dominant disorder.{{OMIM|103580}} It is also associated with thyroid stimulating hormone resistance. Caused by GNAS1 mutation.{{cite journal |vauthors=de Nanclares GP, Fernández-Rebollo E, Santin I, etal |title=Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy |journal=J. Clin. Endocrinol. Metab. |volume=92 |issue=6 |pages=2370–3 |date=June 2007 |pmid=17405843 |doi=10.1210/jc.2006-2287 |doi-access=free }}{{Citation |last=Ucciferro |first=Peter |title=Pseudohypoparathyroidism |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK547709/ |access-date=2025-03-18 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31613489 |last2=Anastasopoulou |first2=Catherine}}

; Type 1b (OMIM {{OMIM|603233||none}})

: Lacks the physical appearance of type 1a, but is biochemically similar.{{OMIM|603233}} It is associated with a methylation defect in the A/B exon of GNAS1, caused by STX16 disruption.{{cite journal |vauthors=Laspa E, Bastepe M, Jüppner H, Tsatsoulis A |title=Phenotypic and molecular genetic aspects of pseudohypoparathyroidism type Ib in a Greek kindred: evidence for enhanced uric acid excretion due to parathyroid hormone resistance |journal=J. Clin. Endocrinol. Metab. |volume=89 |issue=12 |pages=5942–7 |date=December 2004 |pmid=15579741 |doi=10.1210/jc.2004-0249 |url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=15579741|doi-access=free }}{{cite journal |vauthors=Fröhlich LF, Bastepe M, Ozturk D, Abu-Zahra H, Jüppner H |title=Lack of Gnas epigenetic changes and pseudohypoparathyroidism type Ib in mice with targeted disruption of syntaxin-16 |journal=Endocrinology |volume=148 |issue=6 |pages=2925–35 |date=June 2007 |pmid=17317779 |doi=10.1210/en.2006-1298 |doi-access=free }}

; Type 2 (OMIM {{OMIM|203330||none}})

: Also lacks the physical appearance of type 1a.{{OMIM|203330}} Since the genetic defect in type 2 is further down the signalling pathway than in type 1, there is a normal cAMP response to PTH stimulation despite the inherent abnormality in calcium regulation. The specific gene is not identified.

While biochemically similar, type 1 and 2 disease may be distinguished by the differing urinary excretion of cyclic AMP in response to exogenous PTH.{{cn|date=May 2022}}

Some sources also refer to a "type 1c" (OMIM {{OMIM|612462||none}}).{{cite journal |author=Aldred MA |title=Genetics of pseudohypoparathyroidism types Ia and Ic |journal=J. Pediatr. Endocrinol. Metab. |volume=19 |issue=Suppl 2 |pages=635–40 |date=May 2006 |pmid=16789628 |doi=10.1515/jpem.2006.19.s2.635 |s2cid=26538688 }} The phenotype is the same as in type 1a, but red blood cells show normal Gs activity. As it is also caused by a GNAS mutation, it is not clear whether it should be considered an entity separate from Ia.{{cite book |last1=Bastepe |first1=M |title=Genomic Imprinting |chapter=The GNAS Locus and Pseudohypoparathyroidism |series=Advances in Experimental Medicine and Biology |date=2008 |volume=626 |pages=27–40 |pmid=18372789 |doi=10.1007/978-0-387-77576-0_3 |isbn=978-0-387-77575-3 |chapter-url=https://archive.org/details/genomicimprintin0626unse/page/27 }}

Patients may present with features of hypocalcaemia including carpo-pedal muscular spasms, cramping, tetany, and if the calcium deficit is severe, generalized seizures. IQ is typically mildly depressed or unaffected. Additional characteristics include short stature, obesity, developmental delay, and calcification of the basal ganglia in the deep white matter of the brain.{{citation needed|date=September 2020}}

Type 1a pseudohypoparathyroidism is clinically manifest by bone resorption with blunting of the fourth and fifth knuckles of the hand, most notable when the dorsum of the hand is viewed in closed fist position. This presentation is known as 'knuckle knuckle dimple dimple' sign (Archibald's sign). This is as opposed to Turner syndrome which is characterized by blunting of only the fourth knuckle, and Down syndrome, which is associated with a hypoplastic middle phalanx.{{cn|date=September 2021}}

The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal.

• hypocalcemia
• hyperphosphatemia
• elevated parathyroid hormone (hyperparathyroidism)
• Suppressed calcitriol levels{{cite web|last1=Levine|first1=Michael|title=Pseudohypoparathyroidism: A Variation on the Theme of Hypoparathyroidism|url=https://www.hypopara.org/wwwroot/userfiles/files/Pseudohypoparathyroidism0708.pdf|access-date=2014-11-10|archive-date=2016-03-04|archive-url=https://web.archive.org/web/20160304080623/https://www.hypopara.org/wwwroot/userfiles/files/Pseudohypoparathyroidism0708.pdf|url-status=dead}}

Calcium and Calcitriol supplements, the latter with a larger dose than for treatment of hypoparathyroidism.{{citation needed|date=September 2020}}

• Hypoparathyroidism
• Pseudopseudohypoparathyroidism
• Hyperparathyroidism
• Rickets
• Hypervitaminosis D

{{reflist}}

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{{Medical resources

| DiseasesDB = 10835

| ICD10 = {{ICD10|E|20|1|e|20}}

| ICD9 = {{ICD9|275.49}}

| ICDO =

| OMIM = 103580

| OMIM_mult = {{OMIM|603233||none}} {{OMIM|203330||none}}

| MedlinePlus = 000364

| eMedicineSubj = med

| eMedicineTopic = 1940

| MeshID = D011547

}}

{{Parathyroid disease}}

{{Receptor deficiencies}}

{{Genomic imprinting}}

Category:Cell surface receptor deficiencies

Category:Rare diseases