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Hyperphosphatasia-intellectual disability syndrome

MedGen UID:
383800
Concept ID:
C1855923
Disease or Syndrome
Synonym: Hyperphosphatasia with mental retardation syndrome
SNOMED CT: Hyperphosphatasia with seizures and neurologic deficit (33982008); Mabry syndrome (33982008); Hyperphosphatasemia with intellectual disability (33982008); Hyperphosphatasemia with mental retardation (33982008)
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).
 
Related genes: PIGW, PGAP3, PIGY, PIGO, PIGV, PGAP2
 
Monarch Initiative: MONDO:0016596
OMIM® Phenotypic series: PS239300
Orphanet: ORPHA247262

Definition

Mabry syndrome is a condition characterized by intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms.

People with Mabry syndrome have intellectual disability that is often moderate to severe. They typically have little to no speech development and are delayed in the development of motor skills (such as sitting, crawling, and walking). Many affected individuals have low muscle tone (hypotonia) and develop recurrent seizures (epilepsy) in early childhood. Seizures are usually the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness.

Individuals with Mabry syndrome have distinctive facial features that include wide-set eyes (hypertelorism), long openings of the eyelids (long palpebral fissures), a nose with a broad bridge and a rounded tip, downturned corners of the mouth, and a thin upper lip. These facial features usually become less pronounced over time.

Another common feature of Mabry syndrome is shortened bones at the ends of fingers (brachytelephalangy), which can be seen on x-ray imaging. Underdeveloped fingernails (nail hypoplasia) may also occur. Sometimes, individuals with Mabry syndrome have abnormalities of the digestive system, including narrowing or blockage of the anus (anal stenosis or anal atresia) or Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Rarely, affected individuals experience hearing loss.

Hyperphosphatasia begins within the first year of life in people with Mabry syndrome. There are many different types of alkaline phosphatase found in tissues; the type that is increased in Mabry syndrome is called the tissue non-specific type and is found throughout the body. In affected individuals, alkaline phosphatase levels in the blood are usually increased by one to two times the normal amount, but can be up to 20 times higher than normal. The elevated enzyme levels remain relatively stable over a person's lifetime. Hyperphosphatasia appears to cause no negative health effects, but this finding can help health professionals diagnose Mabry syndrome.

The signs and symptoms of Mabry syndrome vary among affected individuals. Those who are least severely affected have only intellectual disability and hyperphosphatasia, without distinctive facial features or the other health problems listed above. [from MedlinePlus Genetics]

Professional guidelines

PubMed

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Recent clinical studies

Etiology

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Diagnosis

Allison R 2nd, Assadzandi S, Adelman M
Am Fam Physician 2021 Feb 15;103(4):219-226. PMID: 33587574
Woolford SJ, Sohan O, Dennison EM, Cooper C, Patel HP
Aging Clin Exp Res 2020 Sep;32(9):1629-1637. Epub 2020 Apr 30 doi: 10.1007/s40520-020-01559-3. PMID: 32356135Free PMC Article
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Therapy

Shafiee E, MacDermid J, Packham T, Walton D, Grewal R, Farzad M
Clin J Pain 2023 Feb 1;39(2):91-105. doi: 10.1097/AJP.0000000000001089. PMID: 36650605
Hon KL, Leung AKC, Torres AR
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O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL
Cochrane Database Syst Rev 2013 Apr 30;2013(4):CD009416. doi: 10.1002/14651858.CD009416.pub2. PMID: 23633371Free PMC Article

Prognosis

Christopher A, Kraft E, Olenick H, Kiesling R, Doty A
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O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL
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Clinical prediction guides

Sanchez-Jimeno C, Blanco-Kelly F, López-Grondona F, Losada-Del Pozo R, Moreno B, Rodrigo-Moreno M, Martinez-Cayuelas E, Riveiro-Alvarez R, Fenollar-Cortés M, Ayuso C, Rodríguez de Alba M, Lorda-Sanchez I, Almoguera B
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Christopher A, Kraft E, Olenick H, Kiesling R, Doty A
Disabil Rehabil 2021 Jun;43(13):1799-1813. Epub 2019 Oct 26 doi: 10.1080/09638288.2019.1682066. PMID: 31656104
Artaza-Artabe I, Sáez-López P, Sánchez-Hernández N, Fernández-Gutierrez N, Malafarina V
Maturitas 2016 Nov;93:89-99. Epub 2016 Apr 14 doi: 10.1016/j.maturitas.2016.04.009. PMID: 27125943
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J Gerontol A Biol Sci Med Sci 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146. PMID: 11253156

Recent systematic reviews

Moreno-Ligero M, Moral-Munoz JA, Salazar A, Failde I
JMIR Mhealth Uhealth 2023 Feb 2;11:e40844. doi: 10.2196/40844. PMID: 36729570Free PMC Article
Valera-Calero JA, Fernández-de-Las-Peñas C, Navarro-Santana MJ, Plaza-Manzano G
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Smart KM, Ferraro MC, Wand BM, O'Connell NE
Cochrane Database Syst Rev 2022 May 17;5(5):CD010853. doi: 10.1002/14651858.CD010853.pub3. PMID: 35579382Free PMC Article
Lew J, Kim J, Nair P
J Man Manip Ther 2021 Jun;29(3):136-146. Epub 2020 Sep 22 doi: 10.1080/10669817.2020.1822618. PMID: 32962567Free PMC Article
Ruiz-González L, Lucena-Antón D, Salazar A, Martín-Valero R, Moral-Munoz JA
J Intellect Disabil Res 2019 Aug;63(8):1041-1067. Epub 2019 Feb 20 doi: 10.1111/jir.12606. PMID: 30788876

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