Hyperphosphatasia with mental retardation syndrome
{{Infobox medical condition (new)
| name = Hyperphosphatasia with mental retardation syndrome
| image = Autosomal recessive - en.svg
| image_size = 240px| caption = This condition is inherited in an autosomal recessive manner
| synonyms = Mabry syndrome
|
| pronounce =
| field =
| symptoms =
| complications =
| onset =
| duration =
| types =
| causes =
| risks =
| diagnosis =
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
Hyperphosphatasia with mental retardation syndrome, HPMRS,{{Cite journal |vauthors=Mabry CC, Bautista A, Kirk RF, Dubilier LD, Braunstein H, Koepke JA |date=July 1970 |title=Familial hyperphosphatase with mental retardation, seizures, and neurologic deficits |journal=The Journal of Pediatrics |volume=77 |issue=1 |pages=74–85 |doi=10.1016/s0022-3476(70)80047-6 |pmid=5465362}} also known as Mabry syndrome,{{Cite journal |display-authors=6 |vauthors=Thompson MD, Nezarati MM, Gillessen-Kaesbach G, Meinecke P, Mendoza-Londono R, Mendoza R, Mornet E, Brun-Heath I, Squarcioni CP, Legeai-Mallet L, Munnich A, Cole DE |date=July 2010 |title=Hyperphosphatasia with seizures, neurologic deficit, and characteristic facial features: Five new patients with Mabry syndrome |journal=American Journal of Medical Genetics. Part A |volume=152A |issue=7 |pages=1661–1669 |doi=10.1002/ajmg.a.33438 |pmid=20578257 |s2cid=2806832 |doi-access=free}} has been described in patients recruited on four continents world-wide.{{Cite journal |vauthors=Thompson MD, Killoran A, Percy ME, Nezarati M, Cole DE, Hwang PA |year=2006 |title=Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure disorder? |journal=Pediatric Neurology |volume=34 |issue=4 |pages=303–307 |doi=10.1016/j.pediatrneurol.2005.08.020 |pmid=16638507}} Mabry syndrome was confirmed{{Cite journal |vauthors=Horn D, Schottmann G, Meinecke P |year=2010 |title=Hyperphosphatasia with mental retardation, brachytelephalangy, and a distinct facial gestalt: Delineation of a recognizable syndrome |journal=European Journal of Medical Genetics |volume=53 |issue=2 |pages=85–88 |doi=10.1016/j.ejmg.2010.01.002 |pmid=20080219}} to represent an autosomal recessive syndrome characterized by severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features that include: hypertelorism, a broad nasal bridge and a rectangular face.
Signs and symptoms
{{Empty section|date=October 2024}}
Pathogenesis
While many cases of HPMRS are caused by mutations in the PIGV gene,{{Cite journal |display-authors=6 |vauthors=Krawitz PM, Schweiger MR, Rödelsperger C, Marcelis C, Kölsch U, Meisel C, Stephani F, Kinoshita T, Murakami Y, Bauer S, Isau M, Fischer A, Dahl A, Kerick M, Hecht J, Köhler S, Jäger M, Grünhagen J, de Condor BJ, Doelken S, Brunner HG, Meinecke P, Passarge E, Thompson MD, Cole DE, Horn D, Roscioli T, Mundlos S, Robinson PN |date=October 2010 |title=Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome |journal=Nature Genetics |volume=42 |issue=10 |pages=827–829 |doi=10.1038/ng.653 |pmid=20802478 |s2cid=205356893}} there may be genetic heterogeneity in the spectrum of Mabry syndrome as a whole. PIGV is a member of the molecular pathway that synthesizes the glycosylphosphatidylinositol anchor.{{Cite journal |display-authors=6 |vauthors=Kang JY, Hong Y, Ashida H, Shishioh N, Murakami Y, Morita YS, Maeda Y, Kinoshita T |date=March 2005 |title=PIG-V involved in transferring the second mannose in glycosylphosphatidylinositol |journal=The Journal of Biological Chemistry |volume=280 |issue=10 |pages=9489–9497 |doi=10.1074/jbc.M413867200 |pmid=15623507 |doi-access=free}} The loss in PIGV activity results in a reduced anchoring of alkaline phosphatase to the surface membrane and an elevated alkaline phosphatase activity in the serum.{{cn|date=November 2020}}
Diagnosis
The clinical diagnosis can be established if the patient has repeatedly elevated levels of alkaline phosphatase activity in the blood serum and exhibits intellectual disability. Supportive for the clinical diagnosis are epilepsies, brachydactyly and a characteristic facial gestalt, which can also be assessed by means of AI.{{Cite journal |display-authors=6 |vauthors=Knaus A, Pantel JT, Pendziwiat M, Hajjir N, Zhao M, Hsieh TC, Schubach M, Gurovich Y, Fleischer N, Jäger M, Köhler S, Muhle H, Korff C, Møller RS, Bayat A, Calvas P, Chassaing N, Warren H, Skinner S, Louie R, Evers C, Bohn M, Christen HJ, van den Born M, Obersztyn E, Charzewska A, Endziniene M, Kortüm F, Brown N, Robinson PN, Schelhaas HJ, Weber Y, Helbig I, Mundlos S, Horn D, Krawitz PM |date=January 2018 |title=Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis |journal=Genome Medicine |volume=10 |issue=1 |pages=3 |doi=10.1186/s13073-017-0510-5 |pmc=5759841 |pmid=29310717 |doi-access=free}} The clinical diagnosis can be confirmed by molecular testing such as exome sequencing.{{cn|date=October 2024}}
Treatment
So far, no effective treatment is available for HPMRS. A mouse model that mirrors the human phenotype has been engineered by CRISPR technology and is available for compound screening.{{Cite journal |display-authors=6 |vauthors=Rodríguez de Los Santos M, Rivalan M, David FS, Stumpf A, Pitsch J, Tsortouktzidis D, Velasquez LM, Voigt A, Schilling K, Mattei D, Long M, Vogt G, Knaus A, Fischer-Zirnsak B, Wittler L, Timmermann B, Robinson PN, Horn D, Mundlos S, Kornak U, Becker AJ, Schmitz D, Winter Y, Krawitz PM |date=January 2021 |title=A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=118 |issue=2 |pages=e2014481118 |bibcode=2021PNAS..11814481R |doi=10.1073/pnas.2014481118 |pmc=7812744 |pmid=33402532 |doi-access=free}}
References
{{Reflist}}
External links
{{Medical resources
| OMIM = 239300
| Orphanet = 247262
}}
{{Phospholipid metabolism disorders}}