Utility of genetic testing for prenatal presentations of hypophosphatasia

Sperelakis-Beedham, Brian; Taillandier, A.; Domingues, Christelle; Guberto, Mihelaiti; Colin, Estelle; Porquet-Bordes, Valérie; Rothenbühler, Anya; Salles, Jean‐Pierre; Wenkert, Deborah; Zankl, Andreas; Muti, Christine; Bacrot, Séverine; Simon‐Bouy, Brigitte; Mornet, Étienne

doi:10.1016/j.ymgme.2021.01.009

Cited by 2 publications

(1 citation statement)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotypic spectrum of HPP is widely variable and depends on the age of onset, the mode of inheritance or the type of gene deletion or duplication. The alleles composing the so far described genotypes are classified according to functional tests; however, not all variants have been tested [ 112 ] and, therefore, the use of genetic testing to predict the phenotype is not always accurate.…”

Section: Managementmentioning

confidence: 99%

Hypophosphatasia

Tournis

Yavropoulou

Polyzos

et al. 2021

JCM

View full text Add to dashboard Cite

Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5΄-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa.

show abstract

Section: Managementmentioning

confidence: 99%

Hypophosphatasia

Tournis

Yavropoulou

Polyzos

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion

Baroncelli,

Carlucci,

Freri

et al. 2023

J Endocrinol Invest

View full text Add to dashboard Cite

Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awareness among health professionals and the lack of official guidelines are responsible for delayed diagnosis in children with HPP. The purpose of the current document is to provide an expert opinion directed at optimizing the diagnostic pathway of pediatric HPP. From April to December 2022, a multidisciplinary working group of 6 experts including two pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist, and a molecular biologist gathered in a series of periodic meetings to discuss the main issues related to the diagnosis of HPP in children and formalize an Expert Opinion statement. The experts agreed on a diagnostic trail that begins with the recognition of specific clinical signs, leading to biochemical analyses of TNSALP activity and vitamin B6 serum concentration. Very important are the neurological and dental manifestation of the disease that should be thoroughly investigated. The evaluation of TNSALP activity must consider sex and age variability and low activity must be persistent. Repeated blood measurements are thus necessary. The molecular analysis is then mandatory to confirm the diagnosis and for genetic counseling.

show abstract

Utility of genetic testing for prenatal presentations of hypophosphatasia

Cited by 2 publications

References 24 publications

Hypophosphatasia

Hypophosphatasia

The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion

Contact Info

Product

Resources

About