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1/Last week we had a case of 
ALP.
We also encountered a pt with
ALP.
Rather than dismiss this as a @UnremarkableLab,
in clinical practice little attention is paid to low ALP activities
#MedStudentTwitter #MedTwitter #FOAMed
ALP.We also encountered a pt with
ALP.Rather than dismiss this as a @UnremarkableLab,
in clinical practice little attention is paid to low ALP activities
#MedStudentTwitter #MedTwitter #FOAMed
2/ALP enzyme was discovered in 1923 and Hypophosphatasia in 1948 by Dr. Rathbun who foundlevels of alkaline phosphatase (ALP) activity in blood and in several tissues from an infant who died with rickets and epilepsy, which seemed to reflect “a new developmental anomaly.”
levels of alkaline phosphatase (ALP) activity in blood and in several tissues from an infant who died with rickets and epilepsy, which seemed to reflect “a new developmental anomaly.”
3/The adult form is characterized by muscle pain, muscle weakness, recurring stress fractures, osteomalacia, a history of dental abnormalities and calcium pyrophosphate dihydrate crystal deposition in the cartilage (CPPD). https://consultqd.clevelandclinic.org/multiple-fractures-low-alp-and-high-b6-in-an-elderly-patient/
4/
Low alkaline phosphatase—and the resulting elevated substrate levels—can lead to morbidities and premature mortality in patients with hypophosphatasia.
In hypophosphatasia, low alkaline phosphatase ruins bones, bodies, and lives
Low alkaline phosphatase—and the resulting elevated substrate levels—can lead to morbidities and premature mortality in patients with hypophosphatasia.
In hypophosphatasia, low alkaline phosphatase ruins bones, bodies, and lives
5/In low APL states, PPI accumulation blocks normal bone formation causing osteomalacia,muscle pain & weakness, recurring stress fractures, dental abnormalities and CPPD. https://hypophosphatasia.com/hcp/about-hpp/understanding-hpp
6/Hypophophatasia in infants can result in PLP deficiency in the CNS which can cause fatal vitamin B6–responsive seizures.
ALP dephosphorylates PLP
PL, allowing it to cross into the CNS.
ALP dephosphorylates PLP
PL, allowing it to cross into the CNS.
7/Within the CNS, PL is rephosphorylated into PLP. Intracellular PLP is involved in neurotransmitter synthesis (eg, gamma aminobutyric acid [GABA], dopamine, serotonin).
HPP canPLP in CNS and contribute to Vitamin B6 responsive seizures.
https://hypophosphatasia.com/hcp/comprehensive-assessment
![7/Within the CNS, PL is rephosphorylated into PLP. Intracellular PLP is involved in neurotransmitter synthesis (eg, gamma aminobutyric acid [GABA], dopamine, serotonin). HPP can PLP in CNS and contribute to Vitamin B6 responsive seizures. https://hypophosphatasia.com/hcp/comprehensive-assessment](https://pbs.twimg.com/media/EssPZj1XMAYMY-A.jpg "7/Within the CNS, PL is rephosphorylated into PLP. Intracellular PLP is involved in neurotransmitter synthesis (eg, gamma aminobutyric acid [GABA], dopamine, serotonin). HPP can PLP in CNS and contribute to Vitamin B6 responsive seizures. https://hypophosphatasia.com/hcp/comprehensive-assessment")
HPP can
PLP in CNS and contribute to Vitamin B6 responsive seizures.https://hypophosphatasia.com/hcp/comprehensive-assessment
8/Other causes of low ALP in adults need to be evaluated prior to pursuing furhter testing for this condition.
9/Interestingly, Micronutrients like Zinc (Zn), Cobolot (Co) and Magnesium (Mg) are important causes of low ALP activity
https://www.foodandnutritionjournal.org/volume5number3/low-alkaline-phosphatase-alp-in-adult-population-an-indicator-of-zinc-zn-and-magnesium-mg-deficiency/
https://www.foodandnutritionjournal.org/volume5number3/low-alkaline-phosphatase-alp-in-adult-population-an-indicator-of-zinc-zn-and-magnesium-mg-deficiency/
10/The Diagnosis can be made by :
- finding low‐serum ALP on routine laboratory testing
- low‐serum ALP is repeated and other causes of low ALP are eliminated
- Checkserum pyridoxal‐5’‐phosphate (vitamin B6) and/or
- urinary of phosphoethanolamine (PEA) support the Dx
- finding low‐serum ALP on routine laboratory testing
- low‐serum ALP is repeated and other causes of low ALP are eliminated
- Check
serum pyridoxal‐5’‐phosphate (vitamin B6) and/or -
urinary of phosphoethanolamine (PEA) support the Dx
11/Clinicians should take notice of persistent hypophosphatasemia, consider the diagnosis of HPP and be cautious when considering potent antiremodeling therapy in these adults since the underlying disorder is a defect in mineralization (osteomalacia), not osteoporosis.
