The Turkish Journal of Pediatrics 2023 , Vol 65 , Num 6
Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report
Gönül Büyükyılmaz 1 ,Keziban Toksoy Adıgüzel 1 ,Özlem Yüksel Aksoy 2 ,Çiğdem Seher Kasapkara 3 ,Gizem Ürel Demir 4 ,Engin Demir 5 ,Şule Berk Ergun 6 ,Fatih Gürbüz 1 ,Mehmet Boyraz 1
1 Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara
2 Department of Pediatric Nefrology, Ankara Bilkent City Hospital, Ankara
3 Department of Pediatric Metabolism and Nutrition, Ankara Bilkent City Hospital, Ankara
4 Department of Pediatric Genetics, Mersin City Hospital, Mersin
5 Department of Pediatric Gastroenterology, Mersin City Hospital, Mersin
6 Department of Ophthalmology, Ankara Bilkent City Hospital, Ankara, Türkiye
DOI : 10.24953/turkjped.2022.187 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. Keywords : sphingolipids, Sphingosine phosphate lyase insufficiency syndrome, adrenal insufficiency, Nephrotic syndrome, Ptosis

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