Hearing Loss Is Part of the Clinical Picture of ENPP1 Loss of Function Mutation

  title={Hearing Loss Is Part of the Clinical Picture of ENPP1 Loss of Function Mutation},
  author={C{\'e}cile Brachet and Anne Laure Mansbach and A. Clerckx and Pierre Deltenre and Claudine Heinrichs},
  journal={Hormone Research in Paediatrics},
  pages={63 - 66}
Background: Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of-function mutations have been described in patients with autosomal recessive hypophosphatemic rickets (HR), in patients with generalized arterial calcification of infancy (GACI) and in several patients with both conditions. Out of more than 50 cases of homozygous or compound heterozygous ENPP1 loss-of-function mutations published so far, 1 case with labyrinthine deafness probably due to occlusion of inner ear… 

Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1

It is confirmed that mild to moderate hearing loss is frequently associated with ARHR2 and early onset conductive hearing loss may further distinguish the autosomal recessive ENPP1 related type from other types of hypophosphatemia.

Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI)

Clinically, this study highlights the importance of early audiologic and otologic evaluation in persons with GACI, and in cases of unclear HL etiology, dedicated temporal bone imaging should be considered.

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While the pathogenic variants are widely distributed in the ENPP1 gene of patientsgen without apparent genotype–phenotype correlation, eight out of nine variants associated with Cole disease are confined to the somatomedin‐B‐like domains critical for homo‐dimerization of the EN PP1 protein.

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The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

Prospective phenotyping of long-term survivors of Generalized Arterial Calcification of Infancy (GACI)

Generalized Arterial Calcification of Infancy appears to be more common than previously thought, with an expanding spectrum of overlapping phenotypes, and the relationships among decreased ENPP1, increased iFGF23, and rickets could inform future therapies.

Embryology, Malformations, and Rare Diseases of the Cochlea

The aim of this work was to provide a clear overview of rare cochlear diseases, taking into account the embryonic development of the cochlea and the systematic presentation of the different disorders.

Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management

Purpose of Review This review summarizes current understanding of generalized arterial calcification of infancy (GACI), emphasizing pathophysiology, clinical presentation, and approaches and

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

There are rare genetic disorders from the group of vitamin D‐resistant rickets where the clinical picture is very similar to the classic forms and diagnosis of genetically conditioned rickets is often delayed.

Generalized Arterial Calcification of Infancy

GACI is inherited in an autosomal recessive manner and patients undergoing treatment of rickets are at risk for nephrocalcinosis and calcifications in other tissues (e.g., liver, pancreas) it is appropriate to maintain urinary excretion of calcium below 4 mg/kg/d.

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.



The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI)

The role of ENPP1 mutations as the main cause of GACI is confirmed and 11 novel homozygous or compound heterozygous mutations are identified, which adds considerably to the mutational spectrum of EN PP1.

Hearing impairment in familial X-linked hypophosphatemic rickets

The hearing status was evaluated in a relatively large group of XLH children in a wide range of ages with that of their afflicted parents and it was found that the only child with hearing impairment was the one with a Mondini inner ear malformation which is believed to result from a developmental arrest of the membranous labyrinth during the first trimester of pregnancy.

Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family.

The results indicate that ANK influences articular soft tissues commonly involved in degenerative joint disorders and provides the first direct evidence for a role of ANK in the central nervous system.

Generalized Arterial Calcification of Infancy: Fatal Clinical Course Associated with a Novel Mutation in ENPP1.

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Efficacy and safety of 2-year etidronate treatment in a child with generalized arterial calcification of infancy

High-dose bisphosphonate therapy may not be necessary for an extended period of time in children with GACI, as the progressive resolution of arterial calcifications seen by 3 months of age was maintained until 2 years of age.

Impaired hearing in X-linked hypophosphataemic (vitamin-D-resistant) osteomalacia.

Sensorineural hearing loss, a previously unrecognised complication of familial hypophosphataemic osteomalacia, occurs frequently and is discussed in the light of pathologic characteristics of familial hyperphosphataemia and its extraosseous manifestations.

Generalized arterial calcification of infancy: Different clinical courses in two affected siblings

Despite the same genotype and similar sonographic and radiographic features in early infancy, the phenotype of GACI can vary to a great extent within one family.

Recessive hypophosphataemic rickets, and possible aetiology of the 'vitamin D-resistant' syndrome.

It is proposed that both syndromes may result from multiple target organ unresponsiveness to 1,25-dihydroxycholecalciferol in intestine, kidney, bone, and parathyroid gland.