Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report

Background. Sphingosine phosphate lyase insufficiency syndrome (SPLIS) caused by inactivating mutations in the human SGPL1 gene results in congenital nephrotic syndrome, adrenal insufficiency, ichthyosis, immunodeficiency, and a wide range of pathological neurological features. We present a n...

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Main Authors: Gönül Büyükyılmaz, Keziban Toksoy Adıgüzel, Özlem Yüksel Aksoy, Çiğdem Seher Kasapkara, Gizem Ürel Demir, Engin Demir, Şule Berk Ergun, Fatih Gürbüz, Mehmet Boyraz
Format: Article
Language:English
Published: Hacettepe University Institute of Child Health 2023-12-01
Series:The Turkish Journal of Pediatrics
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Online Access:https://turkjpediatr.org/article/view/114
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author Gönül Büyükyılmaz
Keziban Toksoy Adıgüzel
Özlem Yüksel Aksoy
Çiğdem Seher Kasapkara
Gizem Ürel Demir
Engin Demir
Şule Berk Ergun
Fatih Gürbüz
Mehmet Boyraz
author_facet Gönül Büyükyılmaz
Keziban Toksoy Adıgüzel
Özlem Yüksel Aksoy
Çiğdem Seher Kasapkara
Gizem Ürel Demir
Engin Demir
Şule Berk Ergun
Fatih Gürbüz
Mehmet Boyraz
author_sort Gönül Büyükyılmaz
collection DOAJ
description Background. Sphingosine phosphate lyase insufficiency syndrome (SPLIS) caused by inactivating mutations in the human SGPL1 gene results in congenital nephrotic syndrome, adrenal insufficiency, ichthyosis, immunodeficiency, and a wide range of pathological neurological features. We present a novel mutation in the SGPL1 gene causing hypocalcemia, primary adrenal insufficiency (PAI), nephrotic syndrome, subclinical hypothyroidism, lymphopenia, ptosis, and pathologic neuroimaging findings. Case. A Turkish male infant presented with bruising at 2 months of age and was diagnosed with hypocalcemia, PAI, and subclinical hypothyroidism. At the age of 15 months, he was admitted to the hospital with ptosis. Other systemic manifestations included persistent lymphopenia and nephrotic syndrome. Magnetic resonance imaging (MRI) of the brain and orbit demonstrated asymmetric contrast enhancement in the left cavernosal sinus, orbital apex, and thinning at the bilateral optic nerve. Whole exome sequencing (WES) revealed a homozygous c.1432C > G (p.Gln478Glu) variant in the SGPL1 gene (NM_003901.4), which has not previously been reported in the literature. Conclusions. Novel mutations in SGPL1 are still being identified. This case reminded us that SPLIS should not be considered for patients with nephrotic syndrome alone. Still, PAI may also include patients with neurological disorders, hypocalcemia, and pathological neuroimaging findings such as thinning at the bilateral optic nerve.
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issn 0041-4301
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language English
publishDate 2023-12-01
publisher Hacettepe University Institute of Child Health
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spelling doaj-art-c665b680151e4d1c8cfdac123b35eb932025-08-20T02:00:50ZengHacettepe University Institute of Child HealthThe Turkish Journal of Pediatrics0041-43012791-64212023-12-0165610.24953/turkjped.2022.187Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case reportGönül Büyükyılmaz0Keziban Toksoy Adıgüzel1Özlem Yüksel Aksoy2Çiğdem Seher Kasapkara3Gizem Ürel Demir4Engin Demir5Şule Berk Ergun6Fatih Gürbüz7Mehmet Boyraz8Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara.Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara.Department of Pediatric Nefrology, Ankara Bilkent City Hospital, Ankara.Department of Pediatric Metabolism and Nutrition, Ankara Bilkent City Hospital, Ankara.Department of Pediatric Genetics, Mersin City Hospital, Mersin.Department of Pediatric Gastroenterology, Mersin City Hospital, Mersin.Department of Ophthalmology, Ankara Bilkent City Hospital, Ankara, Türkiye.Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara.Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara. Background. Sphingosine phosphate lyase insufficiency syndrome (SPLIS) caused by inactivating mutations in the human SGPL1 gene results in congenital nephrotic syndrome, adrenal insufficiency, ichthyosis, immunodeficiency, and a wide range of pathological neurological features. We present a novel mutation in the SGPL1 gene causing hypocalcemia, primary adrenal insufficiency (PAI), nephrotic syndrome, subclinical hypothyroidism, lymphopenia, ptosis, and pathologic neuroimaging findings. Case. A Turkish male infant presented with bruising at 2 months of age and was diagnosed with hypocalcemia, PAI, and subclinical hypothyroidism. At the age of 15 months, he was admitted to the hospital with ptosis. Other systemic manifestations included persistent lymphopenia and nephrotic syndrome. Magnetic resonance imaging (MRI) of the brain and orbit demonstrated asymmetric contrast enhancement in the left cavernosal sinus, orbital apex, and thinning at the bilateral optic nerve. Whole exome sequencing (WES) revealed a homozygous c.1432C > G (p.Gln478Glu) variant in the SGPL1 gene (NM_003901.4), which has not previously been reported in the literature. Conclusions. Novel mutations in SGPL1 are still being identified. This case reminded us that SPLIS should not be considered for patients with nephrotic syndrome alone. Still, PAI may also include patients with neurological disorders, hypocalcemia, and pathological neuroimaging findings such as thinning at the bilateral optic nerve. https://turkjpediatr.org/article/view/114Nephrotic syndromePtosisSphingosine phosphate lyase insufficiency syndromeadrenal insufficiencysphingolipids
spellingShingle Gönül Büyükyılmaz
Keziban Toksoy Adıgüzel
Özlem Yüksel Aksoy
Çiğdem Seher Kasapkara
Gizem Ürel Demir
Engin Demir
Şule Berk Ergun
Fatih Gürbüz
Mehmet Boyraz
Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
The Turkish Journal of Pediatrics
Nephrotic syndrome
Ptosis
Sphingosine phosphate lyase insufficiency syndrome
adrenal insufficiency
sphingolipids
title Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
title_full Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
title_fullStr Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
title_full_unstemmed Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
title_short Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
title_sort novel sphingosine 1 phosphate lyase mutation causes multisystemic diseases case report
topic Nephrotic syndrome
Ptosis
Sphingosine phosphate lyase insufficiency syndrome
adrenal insufficiency
sphingolipids
url https://turkjpediatr.org/article/view/114
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