Albright's hereditary osteodystrophy

Last updated
Albright's hereditary osteodystrophy
Autosomal dominant - en.svg
Albright's hereditary osteodystrophy has an autosomal dominant pattern of inheritance
Specialty Endocrinology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Choroid plexus calcification, Full cheeks [1]
CausesGs alpha subunit deficiency [2]
Diagnostic method calcium, phosphorus, PTH, Urine test for phosphorus and cyclic AMP
TreatmentPhosphate binders, supplementary calcium [3]
Named after Fuller Albright

Albright's hereditary osteodystrophy is a form of osteodystrophy, [4] and is classified as the phenotype of pseudohypoparathyroidism type 1A; this is a condition in which the body does not respond to parathyroid hormone. [1]

Contents

Signs and symptoms

Choroid plexus(bottom left) Gray708.png
Choroid plexus(bottom left)

The disorder is characterized by the following: [1]

Individuals with Albright hereditary osteodystrophy exhibit short stature, characteristically shortened fourth and fifth metacarpals, rounded facies, and often mild intellectual deficiency. [5]

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 ]

Genetics

This condition is associated with genetic imprinting. It is thought to be inherited in an autosomal dominant pattern, and seems to be associated with a Gs alpha subunit deficiency. [2]

Mechanism

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). [6] [7] [8]

Diagnosis

The diagnosis of Albright's hereditary osteodystrophy is based on the following exams below: [9]

Treatment

Treatment consists of maintaining normal levels of calcium, phosphorus, and vitamin D. Phosphate binders, supplementary calcium and vitamin D will be used as required. [3]

History

The disorder bears the name of Fuller Albright, who characterized it in 1942. [12] 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. [13]

See also

Related Research Articles

<span class="mw-page-title-main">Parathyroid gland</span> Endocrine gland

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to a low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in Homo sapiens

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Hypocalcemia</span> Low calcium levels in ones blood serum

Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L while levels less than 2.1 mmol/L are defined as hypocalcemic. Mildly low levels that develop slowly often have no symptoms. Otherwise symptoms may include numbness, muscle spasms, seizures, confusion, or cardiac arrest.

Disorders of calcium metabolism occur when the body has too little or too much calcium. The serum level of calcium is closely regulated within a fairly limited range in the human body. In a healthy physiology, extracellular calcium levels are maintained within a tight range through the actions of parathyroid hormone, vitamin D and the calcium sensing receptor. Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.

<span class="mw-page-title-main">Osteomalacia</span> Softening of bones due to impaired bone metabolism

Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bone metabolism causes inadequate bone mineralization. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. In addition to low systemic levels of circulating mineral ions that result in decreased bone and tooth mineralization, accumulation of mineralization-inhibiting proteins and peptides, and small inhibitory molecules, can occur in the extracellular matrix of bones and teeth, contributing locally to cause matrix hypomineralization (osteomalacia/odontomalacia). A relationship describing local, physiologic double-negative regulation of mineralization has been termed the Stenciling Principle of mineralization, whereby enzyme-substrate pairs imprint mineralization patterns into the extracellular matrix by degrading mineralization inhibitors. The Stenciling Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH).

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany, and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium leaving the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

Renal osteodystrophy/adynamic bone disease is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

<span class="mw-page-title-main">Osteitis fibrosa cystica</span> Medical condition

Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.

Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is inappropriately high. Its pathogenesis has been linked to dysfunctional G Proteins. Pseudohypoparathyroidism is a very rare disorder, with estimated prevalence between 0.3 and 1.1 cases per 100000 population depending on geographic location.

<span class="mw-page-title-main">Tertiary hyperparathyroidism</span> Medical condition

Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone. Anatomically, these glands are located in the neck, para-lateral to the thyroid gland, which does not have any influence in the production of parathyroid hormone. Parathyroid hormone is released by the parathyroid glands in response to low blood calcium circulation. Persistent low levels of circulating calcium are thought to be the catalyst in the progressive development of adenoma, in the parathyroid glands resulting in primary hyperparathyroidism. While primary hyperparathyroidism is the most common form of this condition, secondary and tertiary are thought to result due to chronic kidney disease (CKD). Estimates of CKD prevalence in the global community range from 11 to 13% which translate to a large portion of the global population at risk of developing tertiary hyperparathyroidism. Tertiary hyperparathyroidism was first described in the late 1960s and had been misdiagnosed as primary prior to this. Unlike primary hyperparathyroidism, the tertiary form presents as a progressive stage of resolved secondary hyperparathyroidism with biochemical hallmarks that include elevated calcium ion levels in the blood, hypercalcemia, along with autonomous production of parathyroid hormone and adenoma in all four parathyroid glands. Upon diagnosis treatment of tertiary hyperparathyroidism usually leads to a surgical intervention.

<span class="mw-page-title-main">Follicle-stimulating hormone receptor</span> Protein-coding gene in the species Homo sapiens

The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning of FSH. FSHRs are found in the ovary, testis, and uterus.

<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Protein-coding gene in the species Homo sapiens

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

Pseudopseudohypoparathyroidism (PPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. It is more properly Albright hereditary osteodystrophy although without resistance of parathyroid hormone as frequently seen in that affliction. The term Pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of Pseudohypoparathyroidism type 1a, but has normal labs including calcium and PTH.

<span class="mw-page-title-main">GNAS complex locus</span> Gene locus

GNAS complex locus is a gene locus in humans. Its main product is the heterotrimeric G-protein alpha subunit Gs-α, a key component of G protein-coupled receptor-regulated adenylyl cyclase signal transduction pathways. GNAS stands for Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide.

<span class="mw-page-title-main">Parathyroid hormone 1 receptor</span> Protein-coding gene in the species Homo sapiens

Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).

Gerald D. Aurbach was an American medical scientist noted for his studies of parathyroid diseases, bone metabolism and calcium homeostasis. Aurbach was the first researcher to produce a hormone produced by parathyroid glands.

Archibald's sign refers to a feature in the hand characterized by a shortening of the fourth or/and fifth metacarpals when the fist is clenched.

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare autosomal dominant genetic condition characterized by dwarfism, hypermetropia, microphthalmia, and skeletal abnormalities. This subtype of Kenny-Caffey syndrome is caused by a heterozygous mutation in the FAM111A gene (615292) on chromosome 11q12.

References

PD-icon.svgThis article incorporates text in the public domain from page 798 of the 20th edition of Gray's Anatomy (1918)

  1. 1 2 3 "Albright's hereditary osteodystrophy". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Archived from the original on 11 February 2017. Retrieved 9 February 2017.
  2. 1 2 Kottler, Marie (2004). "Alpha hereditary Osteodystrophy" (PDF). Orphanet.
  3. 1 2 Kliegman, Robert (2016). Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier. pp. chap 572. ISBN   978-1-4557-7566-8.
  4. ↑ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 657. ISBN   978-1-4160-2999-1.
  5. ↑ Garavelli L; Pedori S; Zanacca C; et al. (April 2005). "Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1". Acta Biomed. 76 (1): 45–8. PMID   16116826.
  6. ↑ "OMIM Entry - # 103580 - PSEUDOHYPOPARATHYROIDISM, TYPE IA; PHP1A". omim.org. Retrieved 12 February 2017.
  7. ↑ Cooper, Geoffrey M. (1 January 2000). "Pathways of Intracellular Signal Transduction" . Retrieved 12 February 2017.{{cite journal}}: Cite journal requires |journal= (help)
  8. ↑ Reference, Genetics Home. "What is a gene?". Genetics Home Reference. Retrieved 2017-02-12.
  9. ↑ "Pseudohypoparathyroidism: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 12 February 2017.
  10. ↑ "Pseudohypoparathyroidism".
  11. ↑ Tze, W. J.; Saunders, J.; Drummond, G. I. (1975). "Urinary 3'5' cyclic AMP. Diagnostic test in pseudohypoparathyroidism". Arch Dis Child. 50 (8): 656–658. doi:10.1136/adc.50.8.656. PMC   1545541 . PMID   173244.
  12. ↑ F. Albright, C. H. Burnett, P. H. Smith, et al. Pseudo-hypoparathyroidism-example of 'Seabright-Bantam syndrome'; report of three cases. Endocrinology, Baltimore, 1942, 30: 922-932.
  13. ↑ 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.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.