A rare, inherited, and sometimes fatal metabolic bone disease characterized by poor bone mineralization and profound skeletal defects.Hypophosphatasia (HPP) is caused by mutations within the ALPL gene. This gene provides instructions for making tissue non-specific alkaline phosphatase (TNSALP), an A molecule that catalyzes or triggers biochemical reactions.enzyme that plays a key role in skeletal mineralization that is deficient in individuals with HPP.
About Gene Mutations and TNSALP
Gene mutations that completely eliminate TNSALP activity result in the more severe forms of HPP seen in infants. Milder mutations, those that reduce but do not eliminate the enzyme’s activity, are typically responsible for milder forms of the disease. Approximately 204 distinct mutations have been identified in the ALPL gene.
In HPP, substances that are normally processed by TNSALP, such as Regulates certain intracellular functions and extracellular crystal formation.inorganic pyrophosphate (PPi) and The active form of vitamin B6.pyridoxal 5’-phosphate (PLP; the active form of vitamin B6), accumulate in the body, producing clinical symptoms associated with the disease.
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Inheritance of HPP
The most severe forms of HPP, those that appear before birth and in early infancy, are inherited in an A mode of genetic inheritance in which the phenotypic expression of a gene of interest requires its presence on both paired autosomal (non-sex determining) chromosomes.autosomal recessive pattern, meaning that affected individuals have inherited two copies of the altered gene. Males and females are affected equally.
| Autosomal Recessive Inheritance In autosomal recessive inheritance, each parent carries one copy of the altered gene but do not have symptoms themselves. They are referred to as carriers. In most instances, each sibling of an individual with HPP has a 25% chance of having HPP, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. |
 Autosomal recessive inheritance |
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| Autosomal Dominant Inheritance The milder forms of HPP (childhood, adult, odonto, benign in utero HPP) are inherited in either an autosomal recessive or dominant pattern depending on the effect that the ALPL mutation has on TNSALP activity. A mode of genetic inheritance in which the presence of only one copy of a gene that resides on an autosomal (non-sex determining) chromosome will result in phenotypic expression of that gene.Autosomal dominant inheritance means that just one copy of the altered gene is sufficient to cause disease. |
 Autosomal dominant inheritance |