Pseudohypophosphatasia

Sarkar, Amiya Kumar; Ghosh, Suparna; Mitra, Papia; Mandal, Subinoy; Mukhopadhyay, Samudra; Mathew, Johan

doi:10.1007/bf02752460

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…The nomenclature of pseudo-HPP has sometimes been used to describe apparent cases of HPP wherein clinical presentation overlaps with manifestations of HPP, but where ALP levels are within the normal range (23,24,26,27,(48)(49)(50). Many studies also report cases where clinical signs of HPP are present and ALP is low or normal, and no genetic variant in ALPL can be identified (51)(52)(53)(54)(55).…”

Section: Predicting Dental Manifestations In Patients With Pseudo-hpp...mentioning

confidence: 99%

“…Alpl knockout (Alpl −/− ) mice phenocopy infantile HPP extremely well, including their failure to thrive, high-pitched cries, rickets and extensive hypomineralization of their skeleton, and severe seizures that precede death within a few weeks after birth (though a pyridoxal-enforced diet can reduce seizures and slightly extend lifespan) (20)(21)(22). The term pseudo-HPP has been used to describe apparent cases of HPP where ALP levels are within normal range and may also apply when no genetic variant in ALPL can be identified (23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?

et al. 2022

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Mineralization of the skeleton occurs by several physicochemical and biochemical processes and mechanisms that facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Two key phosphatases, phosphatase, orphan 1 (PHOSPHO1) and tissue-non-specific alkaline phosphatase (TNAP), play complementary roles in the mineralization process. The actions of PHOSPHO1 on phosphocholine and phosphoethanolamine in matrix vesicles (MVs) produce inorganic phosphate (Pi) for the initiation of HA mineral formation within MVs. TNAP hydrolyzes adenosine triphosphate (ATP) and the mineralization inhibitor, inorganic pyrophosphate (PPi), to generate Pi that is incorporated into MVs. Genetic mutations in the ALPL gene-encoding TNAP lead to hypophosphatasia (HPP), characterized by low circulating TNAP levels (ALP), rickets in children and/or osteomalacia in adults, and a spectrum of dentoalveolar defects, the most prevalent being lack of acellular cementum leading to premature tooth loss. Given that the skeletal manifestations of genetic ablation of the Phospho1 gene in mice resemble many of the manifestations of HPP, we propose that Phospho1 gene mutations may underlie some cases of “pseudo-HPP” where ALP may be normal to subnormal, but ALPL mutation(s) have not been identified. The goal of this perspective article is to compare and contrast the loss-of-function effects of TNAP and PHOSPHO1 on the dentoalveolar complex to predict the likely dental phenotype in humans that may result from PHOSPHO1 mutations. Potential cases of pseudo-HPP associated with PHOSPHO1 mutations may resist diagnosis, and the dental manifestations could be a key criterion for consideration.

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Section: Predicting Dental Manifestations In Patients With Pseudo-hpp...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?

et al. 2022

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“…A possible explanation for these normal levels of ALP is the transient correction of hypophosphatasemia as a result of fractures or intercurrent diseases, or slight elevations in the levels of substrates of the enzyme that causes an overexpression of TNSALP [ 93 , 94 ].…”

Section: Diagnosis Of Hppmentioning

confidence: 99%

Hypophosphatasia: A Unique Disorder of Bone Mineralization

Villa-Suárez

García-Fontana

Andújar-Vera

et al. 2021

IJMS

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Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.

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