TNSALP

Tissue-nonspecific alkaline phosphatase (TNSALP) is an alkaline phosphatase isoform encoded by the ALPL gene in humans. It is broadly expressed in liver, bone, kidney, and placenta, and is produced as a single polypeptide that can be membrane-anchored or secreted.

Biochemically, TNSALP is a metalloenzyme requiring zinc and magnesium. It hydrolyzes phosphate esters at alkaline pH and promotes bone and tooth mineralization by dephosphorylating inorganic pyrophosphate (PPi), a key inhibitor of mineral deposition.

Clinical significance centers on hypophosphatasia, a rare inherited disorder caused by low TNSALP activity. It ranges from perinatal lethal to milder odontohypophosphatasia, with skeletal abnormalities, dental problems, and low serum alkaline phosphatase, along with elevated substrates such as pyridoxal-5'-phosphate (PLP) and PPi.

Genetics: ALPL mutations underlie TNSALP deficiency. Most severe forms are autosomal recessive, while some milder cases show autosomal dominant inheritance.

Diagnosis relies on persistently low serum ALP, elevated substrates (PLP, phosphoethanolamine, phosphocholine, PPi), and confirmation by sequencing the ALPL gene.

Treatment includes enzyme replacement therapy with asfotase alfa for pediatric hypophosphatasia and multidisciplinary supportive care. Early diagnosis improves outcomes and quality of life.