Albright's hereditary osteodystrophy: Difference between revisions

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{{about|the subtype of pseudohypoparathyroidism known as Albright's hereditary osteodystrophy|the genetically-related condition| McCune-Albright Syndrome|}}
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{{about|the subtype of pseudohypoparathyroidism known as Albright's hereditary osteodystrophy|the genetically-related condition|McCune–Albright syndrome}}
 
{{Infobox medical condition (new)
{{Infobox medical condition (new)
| name            = Albright's hereditary osteodystrophy
| name            = Albright's hereditary osteodystrophy
| synonyms        =
| image          = Autosomal dominant - en.svg
| image          = Autosomal dominant - en.svg
| caption        = Albright's hereditary osteodystrophy has an autosomal dominant pattern of [[heredity|inheritance]]
| caption        = Albright's hereditary osteodystrophy has an [[autosomal dominant]] pattern of [[inheritance]]
| pronounce      =  
| synonyms        = Acrodysostosis with hormone resistance, AHO
| field          =  
| field          = [[Endocrinology]], [[Medical genetics]]
| symptoms        = Choroid plexus calcification, Full cheeks<ref name=nih/>
| symptoms        = [[Short stature]], [[round facies]], [[brachydactyly]], [[choroid plexus]] calcification, [[dental enamel hypoplasia]], [[intellectual disability]]
| complications  =  
| complications  = [[Hypocalcemia]], [[secondary hyperparathyroidism]], [[tetany]]
| onset          =  
| onset          = [[Childhood]]
| duration        =  
| duration        = [[Lifelong condition]]
| types          =
| causes          = Mutations in the ''[[GNAS]]'' gene
| causes          = Gs alpha subunit deficiency<ref name=or/>
| risks          = Family history of the condition
| risks          =  
| diagnosis      = [[Genetic testing]], [[blood test]]s (serum calcium, PTH), [[urine test]]s, [[MRI]]
| diagnosis      = CBC, Urine test<ref name=medl/>
| differential    = [[Pseudopseudohypoparathyroidism]], [[hypoparathyroidism]], [[McCune–Albright syndrome]]
| differential    =  
| prevention      = None
| prevention      =  
| treatment      = [[Calcium]] and [[vitamin D]] supplementation, [[phosphate binders]]
| treatment      = Phosphate binders, supplementary calcium <ref name=nel/>
| medication      = [[Cholecalciferol]], [[calcitriol]]
| medication      =  
| prognosis      = Good with treatment
| prognosis      =  
| frequency      = Rare
| frequency      =  
| deaths          = Rare due to complications from untreated hypocalcemia
| deaths          =  
}}
}}
'''Albright's hereditary osteodystrophy''' is a form of [[osteodystrophy]],<ref name="Bolognia">{{cite book |author1=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages=657 |isbn=978-1-4160-2999-1 |oclc= |doi= }}</ref> and is classified as the [[phenotype]] of [[pseudohypoparathyroidism]] type 1A; this is a condition in which the body does not respond to [[parathyroid hormone]].<ref
name="nih">{{cite web|title=Albright's hereditary osteodystrophy|publisher=Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |url=https://rarediseases.info.nih.gov/diseases/5770/albrights-hereditary-osteodystrophy |accessdate=9 February 2017 |language=en}}</ref>


==Signs and symptoms==
'''Albright's hereditary osteodystrophy''' ('''AHO''') is a rare inherited [[disorder]] that affects [[bone development]], [[endocrine function]], and certain [[metabolic pathways]]. It is most commonly associated with [[pseudohypoparathyroidism]] type 1A, a condition in which the body exhibits resistance to [[parathyroid hormone]] (PTH). The phenotype includes a constellation of physical abnormalities and hormone resistance syndromes.
The disorder is characterized by the following:<ref name=nih/>
 
*[[Hypogonadism]]
== Overview ==
*[[Brachydactyly]] syndrome
AHO is characterized by a distinct clinical presentation involving skeletal abnormalities, subcutaneous ossifications, and resistance to multiple hormones that signal via [[Gs alpha]] protein-coupled receptors, particularly parathyroid hormone. It is caused by mutations in the ''[[GNAS]]'' gene, which encodes the [[G protein alpha subunit]] (Gsα), critical for [[signal transduction]] in endocrine tissues.
*[[Choroid plexus]] calcification
 
*Hypoplasia of dental enamel
== Signs and Symptoms ==
*Full [[cheeks]]
[[File:Gray708.png|thumb|left|Choroid plexus (bottom left), a site of pathological calcification in AHO.]]
*Hypocalcemic tetany
Patients with AHO often display:
[[File:Gray708.png|thumb|left|Choroid plexus(bottom left)]]
* [[Short stature]]
Individuals with Albright hereditary osteodystrophy exhibit [[short stature]], characteristically shortened fourth and fifth [[metacarpal]]s, rounded [[Facies (medical)|facies]], and often mild intellectual deficiency.<ref name="pmid16116826">{{cite journal |author1=Garavelli L |author2=Pedori S |author3=Zanacca C |display-authors=etal |title=Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1 |journal=Acta Biomed |volume=76 |issue=1 |pages=45–8  |date= April 2005 |pmid=16116826 |doi= |url=}}</ref>
* [[Brachydactyly]] (shortening of the fourth and fifth [[metacarpals]])
* [[Rounded facies]]
* [[Dental enamel hypoplasia]]
* [[Choroid plexus]] calcifications
* [[Subcutaneous calcification]]s
* [[Intellectual disability]] (mild to moderate)
* [[Hypocalcemic tetany]]
* [[Hypogonadism]]
* [[Obesity]] (variable)
These features may overlap with other disorders, making genetic testing important for confirmation.


Albright hereditary osteodystrophy is commonly known as pseudohypoparathyroidism because the kidney responds as if parathyroid hormone were absent. Blood levels of parathyroid hormone are elevated in pseudohypoparathyroidism due to the hypocalcemia{{medical citation needed|date=February 2017}}
== Genetics ==
<br>
AHO is typically inherited in an [[autosomal dominant]] fashion and is caused by mutations in the maternal allele of the ''[[GNAS]]'' gene due to the phenomenon of [[genomic imprinting]]. The gene product, Gsα, is critical for activating [[adenylate cyclase]] and cyclic AMP (cAMP) signaling in response to several [[hormones]].
<br>


==Genetics==
In cases where the mutation is inherited from the father, individuals may display the phenotype without hormone resistance—a condition known as [[pseudopseudohypoparathyroidism]].
This condition is associated with [[genetic imprinting]]. It is thought to be inherited in an [[autosomal]] [[Dominance (genetics)|dominant]] pattern, and seems to be associated with a [[Gs alpha subunit]] deficiency.<ref name="or">{{Cite web|url=https://www.orpha.net/data/patho/GB/uk-AHO.pdf|title=Alpha hereditary Osteodystrophy|last=Kottler|first=Marie|date=2004|website=Orphanet}}</ref>


==Mechanism==
== Pathophysiology ==
The mechanism of this condition is due to Gs signaling decrease in hormones having to do with [[signal transduction]] which is when a signal from outside cell causes change within the cell (in function). [[Renal tubule]] cells only express maternal [[alleles]] (variant form of a gene).<ref>{{cite web|title=OMIM Entry - # 103580 - PSEUDOHYPOPARATHYROIDISM, TYPE IA; PHP1A|url=https://omim.org/entry/103580#phenotypeMap|website=omim.org|accessdate=12 February 2017|language=en-us}}</ref><ref>{{cite journal|last1=Cooper|first1=Geoffrey M.|title=Pathways of Intracellular Signal Transduction|date=1 January 2000|url=https://www.ncbi.nlm.nih.gov/books/NBK9870/|accessdate=12 February 2017|language=en}}</ref><ref>{{Cite web|url=https://ghr.nlm.nih.gov/primer/basics/gene|title=What is a gene?|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2017-02-12}}</ref>
The hallmark of AHO is end-organ resistance to parathyroid hormone. Although PTH levels are elevated due to low [[serum calcium]] and high [[phosphate]], the kidneys fail to respond, leading to hypocalcemia and hyperphosphatemia.


==Diagnosis==
This resistance is due to defective Gsα protein activity in tissues where the maternal allele is the only active copy—such as the [[renal tubules]] and the [[thyroid gland]]—explaining the tissue-specific hormone resistance.
[[File:Hematology Fishbone Schematic.png|thumb|Complete blood count]]
The diagnosis of Albright's hereditary osteodystrophy is based on the following exams below:<ref name="medl">{{cite web|title=Pseudohypoparathyroidism: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/000364.htm|website=medlineplus.gov|accessdate=12 February 2017|language=en}}</ref>
*[[Complete blood count|CBC]]
*[[Urine]] test
*[[MRI]]


==Treatment==
== Diagnosis ==
Treatment consists of maintaining normal levels of calcium, phosphorus, and vitamin D. Phosphate binders, supplementary calcium and vitamin D will be used as required.<ref name="nel">{{Cite book|title=Nelson Textbook of Pediatrics. 20th ed.|last=Kliegman|first=Robert|publisher=Elsevier|year=2016|isbn=978-1-4557-7566-8|location=Philadelphia, PA|pages=chap 572}}</ref>
Diagnosis is clinical and biochemical, confirmed by molecular genetic testing:
* [[Complete blood count]] (CBC)
* Serum calcium: ↓
* Serum phosphate: ↑
* Serum [[parathyroid hormone]] (PTH): ↑
* [[Genetic testing]] for ''GNAS'' mutations
* Imaging: [[MRI]] or [[CT scan]] to assess [[choroid plexus]] calcifications and skeletal anomalies


==History==
== Treatment ==
The disorder bears the name of [[Fuller Albright]], who characterized it in 1942.<ref>F. Albright, C. H. Burnett, P. H. Smith, et al. Pseudo-hypoparathyroidism-example of 'Seabright-Bantam syndrome'; report of three cases.
Management aims to normalize calcium and phosphate levels:
Endocrinology, Baltimore, 1942, 30: 922-932.</ref> He was also responsible for naming it "Sebright bantam syndrome," after the [[Sebright bantam]] chicken, which demonstrates an analogous hormone insensitivity. Much less commonly, the term Martin-Albright syndrome is used, this refers to Eric Martin.<ref>D. Martin, J. Bourdillon. Un cas de tétanie idiopathique chronique. Échec thérapeutique de la graffe d’un adénome parathyroïdien. Revue médicale de la Suisse romande, Lausanne, 1940, 60: 1166-1177.</ref>
* [[Calcium]] supplementation
* [[Vitamin D]] analogs (e.g., [[calcitriol]])
* [[Phosphate binders]]
* Monitoring for associated hormone deficiencies (e.g., [[thyroid-stimulating hormone]], [[gonadotropins]])


== See also ==
Early treatment improves outcomes and reduces the risk of tetany, seizures, and long-term skeletal complications.
* [[Pseudopseudohypoparathyroidism]]


== References ==
== Prognosis ==
{{Reflist}}
With appropriate medical management, patients with AHO can lead normal or near-normal lives. Hormone resistance, if not recognized and treated early, can lead to complications, but the structural anomalies remain lifelong.


==Further reading==
== History ==
*{{cite book|last1=Thakker|first1=Rajesh V.|last2=Whyte|first2=Michael P.|last3=Eisman|first3=John|last4=Igarashi|first4=Takashi|title=Genetics of Bone Biology and Skeletal Disease|date=2013|publisher=Academic Press|isbn=9780123878304|url=https://kiwidental.ca/?id=yz0VLW3Ci5EC&pg=PA437&dq=Albright's+hereditary+osteodystrophy+treatment#v=onepage&q=Albright's%20hereditary%20osteodystrophy%20treatment&f=false|accessdate=12 February 2017|language=en}}
The condition was first described by [[Fuller Albright]] in 1942. Albright observed a unique syndrome combining skeletal malformations with signs of parathyroid hormone resistance, laying the foundation for understanding pseudohypoparathyroidism.
*{{cite book|last1=Henderson|first1=Katherine E.|last2=Baranski|first2=Thomas J.|last3=Bickel|first3=Perry E.|last4=Clutter|first4=William E.|title=The Washington Manual Endocrinology Subspecialty Consult|date=2009|publisher=Lippincott Williams & Wilkins|isbn=9780781791540|url=https://books.google.com/?id=5ir5Zp0pl7oC&pg=PA332&dq=Albright's+hereditary+osteodystrophy+treatment#v=onepage&q=Albright's%20hereditary%20osteodystrophy%20treatment&f=false|accessdate=12 February 2017|language=en}}


== External links ==
== Related Disorders ==
{{Medical resources
* '''[[Pseudopseudohypoparathyroidism]]''': Shares the AHO phenotype but lacks hormone resistance
|  DiseasesDB    = 10835
* '''[[McCune–Albright syndrome]]''': Caused by mosaic ''GNAS'' mutations but presents with endocrine hyperfunction rather than resistance
|  ICD10          = {{ICD10|E|20|1|e|20}}
 
|  ICD9          = {{ICD9|275.49}}
== See Also ==
|  ICDO          =  
* [[Parathyroid hormone]]
|  OMIM          = 103580
* [[Pseudohypoparathyroidism]]
|  MedlinePlus    =  
* [[Endocrine system]]
|  eMedicineSubj  =
* [[Gs alpha subunit]]
|  eMedicineTopic =
* [[Signal transduction]]
|  MeshID        =
* [[Genomic imprinting]]
}}
{{Scholia|topic}}
{{Inborn errors of metal metabolism}}
{{Medicine}}


== External Links ==
* [https://rarediseases.info.nih.gov/diseases/592/albright-hereditary-osteodystrophy NIH Rare Diseases Information]
* [https://omim.org/entry/103580 OMIM Entry on AHO – 103580]
{{Osteochondrodysplasia}}
{{Medical genetics}}
{{Rare diseases}}
[[Category:Autosomal dominant disorders]]
[[Category:Autosomal dominant disorders]]
[[Category:Genodermatoses]]
[[Category:Endocrine diseases]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
{{dictionary-stub1}}
[[Category:Osteodystrophy]]
[[Category:Genetic disorders with endocrinologic manifestations]]

Latest revision as of 01:59, 31 March 2025

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC 


 This article is about the subtype of pseudohypoparathyroidism known as Albright's hereditary osteodystrophy.
   For the genetically-related condition, see McCune–Albright syndrome.



Albright's hereditary osteodystrophy
Synonyms Acrodysostosis with hormone resistance, AHO
Pronounce N/A
Field Endocrinology, Medical genetics
Symptoms Short stature, round facies, brachydactyly, choroid plexus calcification, dental enamel hypoplasia, intellectual disability
Complications Hypocalcemia, secondary hyperparathyroidism, tetany
Onset Childhood
Duration Lifelong condition
Types N/A
Causes Mutations in the GNAS gene
Risks Family history of the condition
Diagnosis Genetic testing, blood tests (serum calcium, PTH), urine tests, MRI
Differential diagnosis Pseudopseudohypoparathyroidism, hypoparathyroidism, McCune–Albright syndrome
Prevention None
Treatment Calcium and vitamin D supplementation, phosphate binders
Medication Cholecalciferol, calcitriol
Prognosis Good with treatment
Frequency Rare
Deaths Rare due to complications from untreated hypocalcemia


Albright's hereditary osteodystrophy (AHO) is a rare inherited disorder that affects bone development, endocrine function, and certain metabolic pathways. It is most commonly associated with pseudohypoparathyroidism type 1A, a condition in which the body exhibits resistance to parathyroid hormone (PTH). The phenotype includes a constellation of physical abnormalities and hormone resistance syndromes.

Overview[edit]

AHO is characterized by a distinct clinical presentation involving skeletal abnormalities, subcutaneous ossifications, and resistance to multiple hormones that signal via Gs alpha protein-coupled receptors, particularly parathyroid hormone. It is caused by mutations in the GNAS gene, which encodes the G protein alpha subunit (Gsα), critical for signal transduction in endocrine tissues.

Signs and Symptoms[edit]

Choroid plexus (bottom left), a site of pathological calcification in AHO.

Patients with AHO often display:

These features may overlap with other disorders, making genetic testing important for confirmation.

Genetics[edit]

AHO is typically inherited in an autosomal dominant fashion and is caused by mutations in the maternal allele of the GNAS gene due to the phenomenon of genomic imprinting. The gene product, Gsα, is critical for activating adenylate cyclase and cyclic AMP (cAMP) signaling in response to several hormones.

In cases where the mutation is inherited from the father, individuals may display the phenotype without hormone resistance—a condition known as pseudopseudohypoparathyroidism.

Pathophysiology[edit]

The hallmark of AHO is end-organ resistance to parathyroid hormone. Although PTH levels are elevated due to low serum calcium and high phosphate, the kidneys fail to respond, leading to hypocalcemia and hyperphosphatemia.

This resistance is due to defective Gsα protein activity in tissues where the maternal allele is the only active copy—such as the renal tubules and the thyroid gland—explaining the tissue-specific hormone resistance.

Diagnosis[edit]

Diagnosis is clinical and biochemical, confirmed by molecular genetic testing:

Treatment[edit]

Management aims to normalize calcium and phosphate levels:

Early treatment improves outcomes and reduces the risk of tetany, seizures, and long-term skeletal complications.

Prognosis[edit]

With appropriate medical management, patients with AHO can lead normal or near-normal lives. Hormone resistance, if not recognized and treated early, can lead to complications, but the structural anomalies remain lifelong.

History[edit]

The condition was first described by Fuller Albright in 1942. Albright observed a unique syndrome combining skeletal malformations with signs of parathyroid hormone resistance, laying the foundation for understanding pseudohypoparathyroidism.

Related Disorders[edit]

See Also[edit]

External Links[edit]

Osteochondrodysplasias
Osteodysplasia/
osteodystrophy
Chondrodysplasia/
chondrodystrophy
(including dwarfism)




Medical genetics
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Disorders
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Treatments
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NIH genetic and rare disease info[edit]

Albright's hereditary osteodystrophy is a rare disease.

Rare and genetic diseases

Rare diseases - Albright's hereditary osteodystrophy

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