Hypophosphatasia: Canadian update on diagnosis and management

Khan, Aliya; Josse, R G; Kannu, Peter; Villeneuve, J; Paul, Terri; Uum, Stan Van; Greenberg, Cheryl R.

doi:10.1007/s00198-019-04921-y

Cited by 32 publications

(35 citation statements)

References 79 publications

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“…Differential diagnoses of low TNSALP activity including osteogenesis imperfecta, multiple myeloma, renal dystrophy, zinc or magnesium deficiency, hypothyroidism, antiresorptive treatment or steroid therapy [1,4] were excluded by further laboratory tests and clinical examination. Vitamin B6 supplementation as a potential confounder of the serum PLP levels was excluded.…”

Section: Patientsmentioning

confidence: 99%

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Genotype–Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia

et al. 2020

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Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a decreased activity of tissue nonspecific alkaline phosphatase (TNSALP). As the onset and severity of HPP are heterogenous, it can be challenging to determine the pathogenicity of detected rare ALPL variants in symptomatic patients. We aimed to characterize patients with rare ALPL variants to propose which patients can be diagnosed with adult HPP. We included 72 patients with (1) clinical symptoms of adult HPP or positive family history and (2) low TNSALP activity and/or high pyridoxal 5′-phosphate (PLP) levels, who underwent ALPL gene sequencing. The patients were analyzed and divided into three groups depending on ALPL variant pathogenicity according to the classification of the American College of Medical Genetics and Genomics (ACMG). Reported pathogenic (n = 34 patients), rare (n = 17) and common (n = 21) ALPL variants only were found. Muscular complaints were the most frequent symptoms (> 80%), followed by bone affection (> 50%). Tooth involvement was significantly more common in patients with pathogenic or rare ALPL variants. Seven rare variants could be classified as likely pathogenic (ACMG class 4) of which five have not yet been described. Inconclusive genetic findings and less specific symptoms make diagnosis difficult in cases where adult HPP is not obvious. As not every pathogenic or rare ALPL variant leads to a manifestation of HPP, only patients with bone complications and at least one additional complication concerning teeth, muscle, central nervous and mental system, repeated low TNSALP activity and high PLP levels should be diagnosed as adult HPP if rare ALPL gene variants of ACMG class 4 or higher support the diagnosis.

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Section: Patientsmentioning

confidence: 99%

“…A total of six clinical subtypes can be differentiated (perinatal, benign prenatal, infantile, childhood, adult, odonto HPP) with continuous overlap [3,4]. Severe forms of HPP have a reported prevalence between 1/100,000 and 1/300,000, whereas milder forms of HPP are more frequent [5].…”

Section: Introductionmentioning

confidence: 99%

Genotype–Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia

et al. 2020

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“…HPP treatment varies depending on its stage and classification and focus on supportive therapy to minimize disease-related systemic manifestations [72,75,77], including: i) Vitamin B6 for seizures in affected patients; ii) Surgery to relieve intracranial pressure or repair fractures, experts recommend managing pseudofractures secondary to hypophosphatasia by internal fixation with a load-bearing device without removal; iii) Pain management, such as NSAIDs. High-dose vitamin D, calcium supplements, and bisphosphonates should not be given when HPP is suspected, as they have been shown to exacerbate symptoms of HPP; iv) Dental care to preserve primary dentition.…”

Section: Treatmentmentioning

confidence: 99%

“…A causal enzyme therapy replacement with asfotase-alfa was approved by FDA in 2015. Asfotase-alfa improves respiratory insufficiency, bone mineralization, and long-term survival, and has a very good safety profile [75,78].…”

Section: Figure 19mentioning

confidence: 99%

Periodontal Disease Associated with Genetic Disorders

Wu¹,

Leung²,

Sun³

2022

Dentistry

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The object of this chapter was to provide an overview including relevant research progress of some genetic disorders with periodontal manifestations. A number of genetic disorders increase patient susceptibility to periodontal disease, with the latter exhibit rather rapid and aggressive presentations. Periodontal disease, perhaps could be the first detectable sign of an undiagnosed genetic disorder. It is therefore important for dental practitioners to be familiar with genetic disorders and their impact on the periodontal tissues. This chapter reviews several genetic disorders that exhibit periodontal manifestations, including hereditary gingival fibromatosis, Papillon-Lefèvre syndrome, cyclic neutropenia, Ehlers-Danlos syndrome and hypophosphatasia.

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“…The etiology of the disease consists of loss-of-function mutations of the ALPL gene on chromosome one, which encodes for tissue nonspecific isoenzyme of alkaline phosphatase (TNAP) [ 7 ]. Earlier onset subtypes are more likely to have an autosomal recessive inheritance pattern, while later-onset subtypes may be inherited in either an autosomal recessive or autosomal dominant pattern [ 8 ].…”

Section: Reviewmentioning

confidence: 99%