Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients

EPGEN Study

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70% were nonambulatory. Epilepsy was present in 80% of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.
Original languageEnglish
Pages (from-to)553-564
JournalJournal of Inherited Metabolic Disease
Volume42
Issue number3
DOIs
Publication statusPublished - 2019

Cite this

@article{603ef8d944824ebea40e1392606b5dea,
title = "Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients",
abstract = "SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70{\%} were nonambulatory. Epilepsy was present in 80{\%} of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.",
author = "{EPGEN Study} and Mari-Anne Vals and Angel Ashikov and Pilvi Ilves and Dagmar Loorits and Qiang Zeng and Rita Barone and Karin Huijben and Jolanta Sykut-Cegielska and Lu{\'i}sa Diogo and Elias, {Abdallah F.} and Greenwood, {Robert S.} and Stephanie Grunewald and {van Hasselt}, {Peter M.} and {van de Kamp}, {Jiddeke M.} and Grazia Mancini and Agnieszka Okninska and Sander Pajusalu and Rudd, {Pauline M.} and Rustad, {Cecilie F.} and Ramona Salvarinova and {de Vries}, {Bert B. A.} and Wolf, {Nicole I.} and Lefeber, {Dirk J.} and Katrin {\~O}unap",
year = "2019",
doi = "10.1002/jimd.12055",
language = "English",
volume = "42",
pages = "553--564",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "3",

}

Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients. / EPGEN Study.

In: Journal of Inherited Metabolic Disease, Vol. 42, No. 3, 2019, p. 553-564.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients

AU - EPGEN Study

AU - Vals, Mari-Anne

AU - Ashikov, Angel

AU - Ilves, Pilvi

AU - Loorits, Dagmar

AU - Zeng, Qiang

AU - Barone, Rita

AU - Huijben, Karin

AU - Sykut-Cegielska, Jolanta

AU - Diogo, Luísa

AU - Elias, Abdallah F.

AU - Greenwood, Robert S.

AU - Grunewald, Stephanie

AU - van Hasselt, Peter M.

AU - van de Kamp, Jiddeke M.

AU - Mancini, Grazia

AU - Okninska, Agnieszka

AU - Pajusalu, Sander

AU - Rudd, Pauline M.

AU - Rustad, Cecilie F.

AU - Salvarinova, Ramona

AU - de Vries, Bert B. A.

AU - Wolf, Nicole I.

AU - Lefeber, Dirk J.

AU - Õunap, Katrin

PY - 2019

Y1 - 2019

N2 - SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70% were nonambulatory. Epilepsy was present in 80% of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.

AB - SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70% were nonambulatory. Epilepsy was present in 80% of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064848845&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30746764

U2 - 10.1002/jimd.12055

DO - 10.1002/jimd.12055

M3 - Article

VL - 42

SP - 553

EP - 564

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 3

ER -