Clinical, Genetic, and Molecular Characterization of Hyperphosphatasia with Mental Retardation: a Case Report and Literature Review

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2019 Nov 6

PMID 31684969

Citations 5

Authors

Layal Abi Farraj

Wassim Daoud Khatoun

Naji Abou Chebel

Victor Wakim

Katia Dawali

Michella Ghassibe-Sabbagh

Affiliations

Soon will be listed here.

Abstract

Background: Hyperphosphatasia with mental retardation syndrome (HPMRS) is a recessive disorder characterized by high blood levels of alkaline phosphatase together with typical dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and developmental delay. Genes involved in the glycosylphosphatidylinositol pathway and known to be mutated in HPMRS have never been characterized in the Lebanese population.

Case Presentation: Herein, we describe a pair of monozygotic twins presenting with severe intellectual disability, distinct facial dysmorphism, developmental delay, and increased alkaline phosphatase level. Two individuals underwent whole exome sequencing followed by Sanger sequencing to confirm the co-segregation of the mutation in the consanguineous family. A biallelic loss of function mutation in PGAP3 was detected. Both patients were homozygous for the c.203delC (p.C68LfsX88) mutation and the parents were carriers confirming the founder effect of the mutation. High ALP serum levels confirmed the molecular diagnosis.

Conclusion: Our findings have illustrated the genomic profile of PGAP3-related HPMRS which is essential for targeted molecular and genetic testing. Moreover, we found previously unreported clinical findings such as hypodontia and skin hyperpigmentation. These features, together with the novel mutation expand the phenotypic and genotypic spectrum of this rare recessive disorder.

Citing Articles

Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases.

Altassan R, Allers M, De Graef D, Shah R, de Vries M, Larson A Mol Genet Metab. 2023; 140(3):107688.

PMID: 37647829 PMC: 10872732. DOI: 10.1016/j.ymgme.2023.107688.

Alkaline phosphatase in clinical practice in childhood: Focus on rickets.

Cannalire G, Pilloni S, Esposito S, Biasucci G, Di Franco A, Street M Front Endocrinol (Lausanne). 2023; 14:1111445.

PMID: 36817604 PMC: 9931734. DOI: 10.3389/fendo.2023.1111445.

Hyperphosphatasia with mental retardation syndrome 3: Cerebrospinal fluid abnormalities and correction with pyridoxine and Folinic acid.

Messina M, Manea E, Cullup T, Tuschl K, Batzios S JIMD Rep. 2023; 64(1):42-52.

PMID: 36636587 PMC: 9830023. DOI: 10.1002/jmd2.12347.

A Novel PGAP3 Gene Mutation-Related Megalocornea Can Be Misdiagnosed as Primary Congenital Glaucoma.

Alhaidari A, Albakri A, Alhumaidi S Cureus. 2022; 14(9):e29387.

PMID: 36304370 PMC: 9585391. DOI: 10.7759/cureus.29387.

Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development.

Daas S, Aamer W, Hasan W, Al-Maraghi A, Al-Kurbi A, Kilani H Cells. 2020; 9(8).

PMID: 32726939 PMC: 7569840. DOI: 10.3390/cells9081782.

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