P-Alp viitearvoista ja kliinisestä merkityksestä , Neuronaali TNAP

Lakartidningen. 2017 Oct 16;114. pii: ETTH.

Tillförlitliga referensintervall krävs för värdering av P-ALP - Nya pediatriska referensintervall för alkaliskt fosfatas har klinisk betydelse för att hitta rätt till diagnosen.

[Article in Swedish]

Magnusson P¹.

Author information

Abstract

Age- and gender-specific reference intervals are pivotal to ensure appropriate interpretation of plasma alkaline phosphatase activities in the lower range Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations of the ALPL gene that mainly express alkaline phosphatase (ALP) in bone and liver. The clinical expression of HPP is highly variable and is classified into six different forms mainly affecting bone and tooth mineralization. The prognosis for each of these HPP forms depends upon the severity of the skeletal disease which reflects the age at presentation. The biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia); however, HPP is often misdiagnosed because of low awareness and sometimes absence of age- and gender-specific ALP reference intervals. Children and adolescents have higher ALP levels in comparison with adults. Reliable reference intervals are pivotal for any clinical laboratory test. Harmonized age- and gender-specific plasma ALP reference intervals ought to be used to ensure appropriate interpretation of plasma ALP activities in the lower range.

http://www.lakartidningen.se/Klinik-och-vetenskap/Kommentar/2017/10/Tillforlitliga-referensintervall-kravs-for-vardering-av-P-ALP/


http://www.socialstyrelsen.se/ovanligadiagnoser/hypofosfatasi#anchor_5



Tästä huomaa että kriittinen kohta fosfaattiaineenvaihdunnassa on sekin että P-ALP käyttää substraattina pyrofosfaatin lisäksi aktiivia B6 vitamiinia jolla on varsin suuri tarve esim myeliinisynteesin aloituksessa. Myeliinin huonosta muodostuksesta tietysti tulee sitä epilepsiaa, johon sitten tehoaa B6- anto jolloin myeliinisynteesi saa alkuainetta aktiivi B6 ja aktiivi seriini kondensoituvat ketosfinganiiniksi jne myeliinitielle se vaatii energiaa tämä synteesitie käsittääkseni. Ilmeisesti  tässä on pahin metabolinen kuoppa koska kyse on samlla keskushermoston kehittymisestä luuston muun fyysisen kehittymisen ohella. Ei tarvitsisi odottaa epileptista kohtausta B6 annon aloitukseen, jos tämä tauti on diagnosoitu.
Siis yksinkertaisesti myeliinia ei muodostu de novo ilman aktiivia B6 vitamiinia.

https://www.ncbi.nlm.nih.gov/pubmed/28072448

https://www.ncbi.nlm.nih.gov/pubmed/22696173

https://www.ncbi.nlm.nih.gov/pubmed/26219720

Subcell Biochem. 2015;76:363-74. doi: 10.1007/978-94-017-7197-9_17.

The Role of Tissue Non-specific Alkaline Phosphatase (TNAP) in Neurodegenerative Diseases: Alzheimer's Disease in the Focus.

Kellett KA¹, Hooper NM.

Abstract

Tissue non-specific alkaline phosphatase (TNAP) is present on neuronal membranes and induces neuronal toxicity via tau dephosphorylation; a mechanism which could play a role in the neuronal loss seen in Alzheimer's disease (AD). TNAP increases in the plasma following brain injury and cerebrovascular disease. In this chapter we summarise our previous work which looked at changes in TNAP activity in the brain and plasma of AD individuals and discuss whether these changes may be reflective of neuronal loss. Our data demonstrate that TNAP activity is significantly increased in the brain in both the sporadic and familial forms of AD and that TNAP activity is significantly increased in the plasma in AD patients. In addition, we describe a significant inverse correlation between plasma TNAP activity and cognitive function in AD. Using these data we propose a model for TNAP-induced neurodegeneration in AD resulting from tau dephosphorylation following secretion of tau from neuronal cells.

PMID:

26219720

DOI:

10.1007/978-94-017-7197-9_17

[Indexed for MEDLINE]