Hyperphosphatasia with mental retardation syndrome type 4 In two siblings-expanding the phenotypic and mutational spectrum

Doğan, Özlem Akgün; Demir, Gizem Ürel; Koşukçu, Can; Taşkıran, Ekim Z.; Şimşek‐Kiper, Pelin Özlem; Ütine, Gülen Eda; Alikaşifoğlu, Mehmet; Boduroğlu, Koray

doi:10.1016/j.ejmg.2018.09.002

Cited by 6 publications

(2 citation statements)

References 13 publications

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“…Three of which were nonsense, 13 were missense, two were small insertion, two were deletion, one mutation was splicing, and one was regulatory. The most commonly reported clinical features of HPMRS are hypertelorism, upslanted palpebral fissures, broad nasal bridge, short nose, seizure disorder, long philtrum, and cleft-palate [3][4][5][6][7][8][9][10][11][15][16]. There are certain uncommon features that were reported in HPMRS4 such as gum hypertrophy, ear pits, and large anterior fontanelle [9].…”

Section: Discussionmentioning

confidence: 99%

“…The most commonly reported clinical features of HPMRS are hypertelorism, upslanted palpebral fissures, broad nasal bridge, short nose, seizure disorder, long philtrum, and cleft-palate [3][4][5][6][7][8][9][10][11][15][16]. There are certain uncommon features that were reported in HPMRS4 such as gum hypertrophy, ear pits, and large anterior fontanelle [9]. Our patient had the same common clinical features, and she had ventricular system dilation in brain MRI, as this finding was reported in previous cases as well.…”

Section: Discussionmentioning

confidence: 99%

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

Alhaidari¹,

AlBakri²,

Alhumaidi³

2022

Cureus

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Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive disorder caused by glycosylphosphatidylinositol (GPI) deficiency. GPI deficiency results from a mutation in one of six known genes. Mutation in post-GPI attachment to protein phospholipase 3 gene (PGAP3) is linked to HPMRS4. Patients usually present with dysmorphic features, developmental delay, central hypotonia, and seizure. However, in our case, we report a novel homozygous missense mutation of PGAP3 gene in a female child who presented with megalocornea, which is an unusual clinical presentation for HPMRS4. Megalocornea, in her first days of life, led to a misdiagnosis of primary congenital glaucoma. Later, other common clinical features of HPMRS4 became apparent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Alhaidari¹,

AlBakri²,

Alhumaidi³

2022

Cureus

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

et al. 2022

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Glycosylphosphatidylinositol anchored proteins (GPI‐APs) represent a class of molecules attached to the external leaflet of the plasma membrane by the GPI anchor where they play important roles in numerous cellular processes including neurogenesis, cell adhesion, immune response and signalling. Within the group of GPI anchor defects, six present with the clinical phenotype of Hyperphosphatasia with Mental Retardation Syndrome (HPMRS, Mabry Syndrome) characterized by moderate to severe intellectual disability, dysmorphic features, hypotonia, seizures and persistent hyperphosphatasia. We report the case of a 5‐year‐old female with global developmental delay associated with precocious puberty and persistently raised plasma alkaline phosphatase. Targeted next generation sequencing analysis of the HPMRS genes identified novel compound heterozygous variants in the PGAP2 gene (c.103del p.(Leu35Serfs*90)and c.134A > Gp.(His45Arg)) consistent with the diagnosis of HPMRS type 3. Cerebrospinal fluid (CSF) neurotransmitter analysis showed low levels of pyridoxal phosphate and 5‐methyltetrahydrofolate and raised homovanillic acid. Supplementation with pyridoxine and folinic acid led to normalization of biochemical abnormalities. The patient continues to make developmental progress with significant improvement in speech and fine motor skills. Our reported case expands the clinical spectrum of HPMRS3 in which multisystem involvement is being increasingly recognized. Furthermore, it shows that miss‐targeting GPI‐APs and the effect on normal cellular function could provide a physiopathologic explanation for the CSF biochemical abnormalities with management implications for a group of disorders that currently has no treatment that can lead possibly to improved clinical outcomes.

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Diseases Associated With GPI Anchors

Murakami

2021

Comprehensive Glycoscience

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Hyperphosphatasia with mental retardation syndrome type 4 In two siblings-expanding the phenotypic and mutational spectrum

Cited by 6 publications

References 13 publications

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

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

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

Diseases Associated With GPI Anchors

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