Hypophosphatasia

Fenn, Jonathan; Lorde, Nathan; Ward, John Martin; Borovickova, Ingrid

doi:10.1136/jclinpath-2021-207426

Cited by 18 publications

(17 citation statements)

References 58 publications

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“…The manifestations of HPP in children cover a broad spectrum of severity but are also classified as discrete clinical subtypes (21). In the most severe forms of the perinatal lethal subtype, children who survive childbirth are born with skeletal hypomineralization and typically succumb to respiratory failure (19).…”

Section: Primary Metabolic Bone Disorders 21 Hypophosphatasiamentioning

confidence: 99%

Transition of young adults with metabolic bone diseases to adult care

Ross

Bowden

et al. 2023

Front. Endocrinol.

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As more accurate diagnostic tools and targeted therapies become increasingly available for pediatric metabolic bone diseases, affected children have a better prognosis and significantly longer lifespan. With this potential for fulfilling lives as adults comes the need for dedicated transition and intentional care of these patients as adults. Much work has gone into improving the transitions of medically fragile children into adulthood, encompassing endocrinologic conditions like type 1 diabetes mellitus and congenital adrenal hyperplasia. However, there are gaps in the literature regarding similar guidance concerning metabolic bone conditions. This article intends to provide a brief review of research and guidelines for transitions of care more generally, followed by a more detailed treatment of bone disorders specifically. Considerations for such transitions include final adult height, fertility, fetal risk, heritability, and access to appropriately identified specialists. A nutrient-dense diet, optimal mobility, and adequate vitamin D stores are protective factors for these conditions. Primary bone disorders include hypophosphatasia, X-linked hypophosphatemic rickets, and osteogenesis imperfecta. Metabolic bone disease can also develop secondarily as a sequela of such diverse exposures as hypogonadism, a history of eating disorder, and cancer treatment. This article synthesizes research by experts of these specific disorders to describe what is known in this field of transition medicine for metabolic bone diseases as well as unanswered questions. The long-term objective is to develop and implement strategies for successful transitions for all patients affected by these various conditions.

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Section: Primary Metabolic Bone Disorders 21 Hypophosphatasiamentioning

confidence: 99%

Transition of young adults with metabolic bone diseases to adult care

Ross

Bowden

et al. 2023

Front. Endocrinol.

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“…There is high allelic heterogeneity and can be inherited in an autosomal dominant or recessive pattern. 17,29 -31…”

Section: Inherited Dental Conditionsmentioning

confidence: 99%

A Review of Selected Dental Anomalies With Histologic Features in the Pediatric Patient

Schultz,

Penner

2023

Pediatr Dev Pathol

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Unique dental conditions in children include odontogenic cysts and tumors, hereditary dental diseases, developmental anomalies, and lesions associated with the eruption of the primary or permanent teeth. Many of these conditions have long lasting effects on the adult dentition in terms of affecting esthetics, function, and overall quality of life. Inherited dental syndromes affect the dental hard tissues specifically the enamel, dentin, and/or cementum in a generalized manner, involving both primary and permanent teeth. These conditions manifest in altered quality or quantity of the hard tissues, leading to fragility, tooth loss and dental diseases such as caries, periapical pathology, and periodontal disease. This category includes amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasia, hypophosphatasia, and hypophosphatemia. Developmental defects such as regional odontodysplasia are defined by involvement of the primary and permanent dentition in a localized manner, identified in early childhood. This review will elaborate on the histologic findings in these selected dental conditions with a discussion on clinical and radiographic findings, as well as molecular features wherever appropriate.

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“…showed that, the estimated prevalence of mild HPP could be double that of previously reported estimation for Spanish population (1/3,100 vs. 1/6,370), and there could be more than 15,000 potential patients affected with mild forms of HPP underdiagnosed due to a lack of recognition in clinical practice ( 3 ). The clinical manifestations and prevalence of HPP has changed significantly between 1997 and 2019 from a rare and mostly recessive bone disease to a multisystemic, mostly dominant and frequent disease in its moderate and mild form ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…In humans, the ALPI, ALPP, ALPPL2 and ALPL genes encode intestinal (IALP), placental (PALP), tissue-specific germ cell (GCALP) and non-tissue-specific (TNSALP) ALP isoenzymes, respectively ( 4 ). The role of ALP is to hydrolyze phosphomonoesters with the release of inorganic phosphate ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia

et al. 2022

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Hypophosphatasia (HPP) a rare disease caused by mutations in the ALPL gene encoding for the tissue-nonspecific alkaline phosphatase protein (TNSALP), has been identified as a potentially under-diagnosed condition worldwide which may have higher prevalence than currently established. This is largely due to the overlapping of its symptomatology with that of other more frequent pathologies. Although HPP is usually associated with deficient bone mineralization, the high genetic variability of ALPL results in high clinical heterogeneity, which makes it difficult to establish a specific HPP symptomatology. In the present study, three variants of ALPL gene with uncertain significance and no previously described (p.Del Glu23_Lys24, p.Pro292Leu and p.His379Asn) were identified in heterozygosis in patients diagnosed with HPP. These variants were characterized at phenotypic, functional and structural levels. All genetic variants showed significantly lower in vitro ALP activity than the wild-type (WT) genotype (p-value <0.001). Structurally, p.His379Asn variant resulted in the loss of two Zn2+ binding sites in the protein dimer which may greatly affect ALP activity. In summary, we identified three novel ALPL gene mutations associated with adult HPP. The correct identification and characterization of new variants and the subsequent study of their phenotype will allow the establishment of genotype-phenotype relationships that facilitate the management of the disease as well as making it possible to individualize treatment for each specific patient. This would allow the therapeutic approach to HPP to be personalized according to the unique genetic characteristics and clinical manifestations of each patient.

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Hypophosphatasia

Cited by 18 publications

References 58 publications

Transition of young adults with metabolic bone diseases to adult care

Transition of young adults with metabolic bone diseases to adult care

A Review of Selected Dental Anomalies With Histologic Features in the Pediatric Patient

Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia

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