scholarly journals Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia

2001 ◽  
Vol 18 (1) ◽  
pp. 83-84 ◽  
Author(s):  
A. Taillandier ◽  
A.S. Lia-Baldini ◽  
M. Mouchard ◽  
B. Robin ◽  
F. Muller ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Novel Mutations ◽  
Tissue Nonspecific Alkaline Phosphatase

scholarly journals FrancisellaDnaK Inhibits Tissue-nonspecific Alkaline Phosphatase

2012 ◽  
Vol 287 (44) ◽  
pp. 37185-37194 ◽  
Author(s):  
Bernard P. Arulanandam ◽  
Senthilnath Lakshmana Chetty ◽  
Jieh-Juen Yu ◽  
Sean Leonard ◽  
Karl Klose ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Tissue Nonspecific Alkaline Phosphatase

scholarly journals Case of Juvenile Onset Hypophosphatasia Diagnosed in an Adult Patient

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A187-A188
Author(s):  
Nirmal Nair
Keyword(s):  
Alkaline Phosphatase ◽  
Dental Caries ◽  
Ankle Fracture ◽  
Vitamin B6 ◽  
Serum Alkaline Phosphatase ◽  
Bone Mineralization ◽  
Multiple Fractures ◽  
History Of ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Low Serum

Abstract Background: Hypophosphatasia is a rare multisystem disease caused by mutations in genes encoding tissue nonspecific alkaline phosphatase, a key player in promoting bone mineralization1. Here we present a case of hypophosphatasia in a patient with history of recurrent fractures and dental caries since childhood. Case Report: Patient is a 52-year-old woman with history of multiple fractures who initially presented for follow up of osteoporosis following an atraumatic ankle fracture. Further questioning revealed a history of 16 atraumatic fractures since the age of 4, involving ankles, toes, and fingers. Several adult teeth had never developed requiring braces to fill in gaps at age 13, dental caries and tooth fractures involving the majority of her adult teeth. DEXA scan in 2019 revealed T score of -2.4 in the left femoral neck. Suspicion for hypophosphatasia in February 2019 following an ankle fracture and patient’s prior history prompted further workup, revealing low serum alkaline phosphatase levels of 29 and 32 (bone fraction 62 percent, liver fraction 38 percent), and Vitamin B6 levels elevated to 66.2. Remainder of workup, with Vitamin D, PTH, Magnesium, and Calcium was normal. A childhood history of multiple atraumatic fractures, various dental issues, with elevated Vitamin B6 and low serum alkaline phosphatase suggested Hypophosphatasia. As bisphosphonates are contraindicated in these patients due to their potential to reduce ALP, teriparatide was initiated. Discussion: Hypophosphatasia involves mutations in tissue nonspecific alkaline phosphatase, a key player in bone mineralization. In normal individuals, this enzyme dephosphorylates inorganic pyrophosphate (PPi), which otherwise inhibits bone mineralization. The mutated TNSALP leads to accumulation of PPi, and thereby unmineralized osteoid.1 Although individual presentations can vary, developmental abnormalities, such as delayed growth, early loss of primary or secondary teeth, or history of multiple fractures are characteristic. Due to the rarity of the disease, and its potential to be confused for more common bone and rheumatologic diseases, diagnosis is often delayed1. Patients in whom suspicion for hypophosphatasia is present, should undergo further testing with bone specific Alkaline phosphatase and Vitamin B6 which would be low and elevated, respectively and may be candidates for enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase1. Traditional treatments such as bisphosphonates potentially decrease ALP and worsen disease, making accurate diagnosis all the more crucial. References1 Bishop N. Clinical management of hypophosphatasia. Clin Cases Miner Bone Metab. 2015;12(2):170–173.

scholarly journals Tissue-Nonspecific Alkaline Phosphatase Is Required for MC3T3 Osteoblast–Mediated Protection of Acute Myeloid Leukemia Cells from Apoptosis

2018 ◽  
Vol 201 (3) ◽  
pp. 1086-1096 ◽  
Author(s):  
Rosalie M. Sterner ◽  
Kimberly N. Kremer ◽  
Amel Dudakovic ◽  
Jennifer J. Westendorf ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Acute Myeloid Leukemia Cells ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Acute Myeloid

Abstract 426: Overexpression of Tissue-nonspecific Alkaline Phosphatase (TNAP) Accelerates Coronary Artery Disease in the Setting of Hypercholesterolemia in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Filippo Romanelli ◽  
AnthonyMarco Corbo ◽  
Maryam Salehi ◽  
Manisha C Yadav ◽  
Soha Salman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Alkaline Phosphatase ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Vascular Calcification ◽  
Coronary Atherosclerosis ◽  
Atherogenic Diet ◽  
Arterial Calcification ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Artery Disease

Objective: Vascular calcification in asymptomatic individuals is an independent predictor of coronary heart disease (CHD). It is therefore plausible that vascular calcification plays a direct pathophysiological role in atherosclerosis, an underlying cause of CHD. The purpose of this study was to examine the contribution that vascular calcification has on the development of coronary atherosclerosis in a mouse model of familial hypercholesterolemia. Approach and Results: Calcification was induced by overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells of mice harboring a point mutation in the low density lipoprotein receptor ( ldlr, wicked high cholesterol, WHC). Mice were fed an atherogenic diet; echocardiographic and biochemical data were collected longitudinally. Atherosclerosis and vascular calcification were analyzed histologically in the aorta, aortic sinus and coronary arteries. TNAP mice were also treated with a combination of an atherogenic diet and a specific inhibitor of TNAP (SBI-425). Combined with the ldlr mutation and an atherogenic diet, TNAP-driven arterial calcification led to severe atherosclerosis with 100% morbidity characterized by occlusive coronary artery disease, pathological cardiac hypertrophy with dilated LV and reduced ejection fraction (EF). We detected an interaction between vascular calcification and atherosclerosis in mice with endothelial TNAP overexpression. This interaction was particularly prominent in coronary circulation. Targeting TNAP activity therapeutically helped improve survival and heart function of endothelial TNAP overexpressor mice, however the incomplete inhibition of TNAP by SBI-425 was a limitation of this study. Conclusions: Vascular calcification via TNAP overexpression in endothelial cells promotes coronary atherosclerosis and is pathogenic under conditions of hypercholesterolemia.

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