The CARE guidelines were followed in the presentation of this case. [bmcmedgenet.biomedcentral.com]

Clinical presentations included; 6/6 developmental delay, 5/6 epileptic encephalopathy, 6/6 hypotonia, 4/6 growth failure, 3/6 dysmorphism, 5/6 neuroimaging abnormalities, 5/6 skeletal abnormalities. [adc.bmj.com]

Affected individuals may also present with eye, skin, and cardiac disease, as well as facial dysmorphisms. [atm.amegroups.com]

Discussion We presented four new patients with typical features of SLC35A2-CDG carrying de novo and deleterious mutations in SLC35A2 gene. [frontiersin.org]

The important thing to remember is that if a child presents with symptoms such as developmental delay, organ failure and failure to thrive, then to suspect CDG. [cdg-uk.org]

• Developmental Delay

  Affected infants may have seizures (such as hypsarrhythmia), low muscle tone, global developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). [fcdgc.rarediseasesnetwork.org]

  Mendelian Rare Diseases CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIm; CDG2M Slc35a2-cdg Description SLC35A2-CDG is a congenital disorder of glycosylation characterized by severe or profound global developmental delay, early epileptic encephalopathy, [mendelian.co]

  Discussion Our data support previous reports on SLC35A2-CDG, confirming that the main features are developmental delay, intractable seizures, abnormal neuroimaging and hypotonia. [adc.bmj.com]

  delay, early epileptic encephalopathy, muscular hypotonia, dysmorphic features (coarse facies, thick eyebrows, broad nasal bridge, thick lips, inverted nipples), variable ocular defects and brain morphological abnormalities on brain MRI (cerebral atrophy [rarediseases.info.nih.gov]

  Symptoms of CDG in infancy and childhood may include: low muscle tone or floppiness (hypotonia) poor growth, failure to thrive developmental delays liver disease (hepatopathy) with elevated liver enzymes abnormal bleeding or blood clotting misaligned [chop.edu]

• Epilepsy

  Slc35a2-cdg Recommended genes panels Panel Name, Specifity and genes Tested/covered Epilepsy Advanced Sequencing and CNV Evaluation - Generalized, Absence, Focal,Febrile and Myoclonic Epilepsies. By Athena Diagnostics Inc (United States). [mendelian.co]

  A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: clinical features and treatment for epilepsy. [frontiersin.org]

  A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy. Brain Dev. 2017 Mar;39(3):256-260. doi: 10.1016/j.braindev.2016.09.009. Epub 2016 Oct 12. [medlineplus.gov]

  […] thickening liquid foods or the use of a nasogastric (NG) tube or G-tube early intervention with occupational, speech and physical therapy for developmental delays, and ongoing therapy through childhood and adolescence as needed antiepileptic medication or epilepsy [chop.edu]

  PIGN mutations cause congenital anomalies, developmental delay, hypotonia, epilepsy, and progressive cerebellar atrophy. Neurogenetics. 2014;15:85-92. http://www.ncbi.nlm.nih.gov/pubmed/24253414 Maydan G, Noyman I, Har-Zahav A, et al. [rarediseases.org]

• Feeding Difficulties

  difficulties Wide nasal bridge Hypoplasia of the corpus callosum And another 20 symptoms. [mendelian.co]

  Affected children may have feeding difficulties and fail to grow or gain weight at the expected rate. Some have vision or hearing problems. [encyclopedia.pub]

  At birth, resuscitation was required, followed by neonatal jaundice and feeding difficulties. During the first year of life, the patient had central hypotonia, gross motor delay, and failure to thrive. [bmcmedgenet.biomedcentral.com]

• Weakness

  Individuals with SLC35A2-CDG often have abnormal brain function (encephalopathy), unusual facial features, skeletal abnormalities, and weak muscle tone (hypotonia) with poor head control. [encyclopedia.pub]

  Depending on the specific type of CDG, common signs and symptoms include: Developmental delays Imbalance Muscle weakness Nerve damage Vision issues Gastrointestinal problems Poor growth Liver disease Bone disease Heart disease Hormone problems Low blood [mayoclinic.org]

  More mild forms of alpha dystroglycanopathies may only affect the muscles, resulting in weakness that is not apparent until adulthood. GPI-anchor synthesis defects. [cdgcare.org]

• Anemia

  Laboratory abnormalities may include elevated liver enzymes, abnormal coagulation factor activities, thrombocytopenia, and anemia. There are more than 60 SLC35A2-CDG patients published in the medical literature. [fcdgc.rarediseasesnetwork.org]

  Subject will not be eligible if they have aldolase-B deficiency, galactosemia, hemolytic uremic syndrome, or severe anemia; or if they have experienced severe AEs (severe diarrhea, vomiting, constipation, galactosuria, or increased liver glycogen storage [clinicaltrials.gov]

  However, one patient (P1) in our cohort had anemia and hypertriglyceridemia, while another patient (P2) had hypertonia. All of which have never been reported in previous reports and could be novel phenotypes of SLC35A2-CDG. [frontiersin.org]

  BOTH monoallelic and biallelic, autosomal or pseudoautosomal Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Dyserythropoietic anemia [panelapp.genomicsengland.co.uk]

• Constipation

  Subject will not be eligible if they have aldolase-B deficiency, galactosemia, hemolytic uremic syndrome, or severe anemia; or if they have experienced severe AEs (severe diarrhea, vomiting, constipation, galactosuria, or increased liver glycogen storage [clinicaltrials.gov]

• Hearing Problem

  Some have vision or hearing problems. In SLC35A2-CDG, medical imaging shows loss of tissue (atrophy) in parts of the brain called the cerebrum and cerebellum. [encyclopedia.pub]

• Muscle Weakness

  Depending on the specific type of CDG, common signs and symptoms include: Developmental delays Imbalance Muscle weakness Nerve damage Vision issues Gastrointestinal problems Poor growth Liver disease Bone disease Heart disease Hormone problems Low blood [mayoclinic.org]

• Muscle Cramp

  cramps, and signs suggesting rhabdomyolysis). [clinicaltrials.gov]

• Suggestibility

  […] be closely monitored for clinical signs and symptoms related to or suspected to be related to withdrawal of D-galactose therapy (e.g., fasting blood glucose <50 mg/dl, hypoglycemic episode, bleeding, persistent or recurrent muscle cramps, and signs suggesting [clinicaltrials.gov]

  These findings suggest that complicated patterns of X-chromosome inactivation may play a role in phenotypic severity in SLC35A2-CDG. [bmcmedgenet.biomedcentral.com]

  Doctors with experience in diagnosing the various forms of CDG suggest that CDG be considered as a possible diagnosis whenever a person has unexplained symptoms affecting multiple body systems or when a single health problem cannot be otherwise explained [chop.edu]

  She developed seizures at the age of 10 months, EEG results were suggestive of infantile spasm (intermittent hypsarrhythmia with focal sharp waves on temporal-occipital lobe). [frontiersin.org]

  Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med 2018;20:435-43. [Crossref] [PubMed] Dragojlovic N, Elliott AM, Adam S, et al. [atm.amegroups.com]

• Thick Lips

  […] eyebrows, broad nasal bridge, thick lips, inverted nipples), variable ocular defects and brain morphological abnormalities on brain MRI (cerebral atrophy, thin corpus callosum). [mendelian.co]

  […] ears, mid-face hypoplasia, full cheek, depressed/broad nasal bridge, short nose, upturned nares, hypoplastic alae nasi, long, or short philtrum, thick lips, prominent cupid’s bow, protruding tongue, fused tooth, enamel hypoplasia, high-arched palate, [frontiersin.org]

• Coarse Face

  Previously reported facial dysmorphisms included brachycephaly, coarse face, hypertelorism, high-set/broad/thick eyebrows, large blue irises, long narrow palpebral fissures, eversion of the lower lids, long eyelashes, epicanthal folds, low-set/posteriorly-rotated [frontiersin.org]

• Seizure

  Affected infants may have seizures (such as hypsarrhythmia), low muscle tone, global developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). [fcdgc.rarediseasesnetwork.org]

  SCN2A, ST3GAL3, SLC35A2, SPTAN1, CDKL5, STXBP1, CACNA2D1, ARX, SLC25A22, ADSL, TBL1XR1, FOXG1, GABRB3, GRIN2A, MEF2C, NR2F1 Specificity 7 % Genes 100 % NGS Epilepsy/Seizure Panel. [mendelian.co]

  She presented with seizure at the age of 3 months, hypsarrhythmia in electroencephalogram (EEG) indicated infantile spasms. Seizures significantly improved after treatment with topiramate and vigabatrin. [frontiersin.org]

  In some individuals, the seizures do not improve with anti-epileptic medications. [encyclopedia.pub]

• Encephalopathy

  View the complete list with 214 more genes Specificity 1 % Genes 100 % Epilepsy Advanced Sequencing and CNV Evaluation-Epileptic Encephalopathy. By Athena Diagnostics Inc (United States). [mendelian.co]

  EARLY INFANTILE, 22; EIEE22CDG syndrome type IIm; CDG-IIm; CDG2M; Congenital disorder of glycosylation type 2m; Congenital disorder of glycosylation type IIm; Congenital disorder of glycosylation, type IIm; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, [rarediseases.info.nih.gov]

  Individuals with SLC35A2-CDG often have abnormal brain function (encephalopathy), unusual facial features, skeletal abnormalities, and weak muscle tone (hypotonia) with poor head control. [medlineplus.gov]

• Hypsarrhythmia

  Affected infants may have seizures (such as hypsarrhythmia), low muscle tone, global developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). [fcdgc.rarediseasesnetwork.org]

  She developed seizures at the age of 10 months, EEG results were suggestive of infantile spasm (intermittent hypsarrhythmia with focal sharp waves on temporal-occipital lobe). [frontiersin.org]

  All reported patients, including the current one, had brain MRI abnormalities (Table 1) and had neurological symptoms ranging from developmental delay and hypotonia to early onset infantile encephalopathy with severe seizures and hypsarrhythmia. [bmcmedgenet.biomedcentral.com]

  The best-characterized GPI biosynthesis defect, X-linked PIGA deficiency, presents with infantile spasms with hypsarrhythmia, hypotonia, multiple brain abnormalities, and facial dysmorphisms. [atm.amegroups.com]

• Hypoglycemia

  Subjects will be instructed to measure fasting blood glucose level by glucometer daily and whenever they have symptoms of hypoglycemia during the washout period. [clinicaltrials.gov]

  D-galactose at 1.0–2.5 g/kg/day (max 50 grams) has been demonstrated to improve the hypoglycemia, coagulopathy, and endocrinopathy in PGM1-CDG (85,86). [atm.amegroups.com]

  For instance, patients with PGM1-CDG (a type 1 disorder of N-glycosylation) frequently have hypoglycemia, hormonal dysregulations, growth delay, seizures, cleft lip and/or palate, a uvula that is split in two (bifid uvula), myopathy and bleeding. [rarediseases.org]

Treatment and Prognosis There is a potential nutritional intervention treatment for SLC35A2-CDG, by oral D-galactose supplementation (D-galactose 1.5 g/kg/day, maximum dose 50 g/day). This treatment is still being tested on a research basis. [fcdgc.rarediseasesnetwork.org]

This is a multicenter, open-label, withdrawal and treatment study assessing the efficacy, safety, and tolerability of CERC-801 in subjects with SLC35A2-CDG. [clinicaltrials.gov]

Most will need a team of medical specialists to monitor their health over time and adjust needed treatments. [chop.edu]

Treatments may make the body healthy but you cannot, unfortunately, fix the brain if impaired development or damage is already evident. [cdg-uk.org]

Most CDG types do not have specific treatment or cures available. However, many of the health concerns in CDG are treatable. Current treatment for CDG patients involves screening for and treatment of health concerns. [cdgcare.org]

Treatment and Prognosis There is a potential nutritional intervention treatment for SLC35A2-CDG, by oral D-galactose supplementation (D-galactose 1.5 g/kg/day, maximum dose 50 g/day). This treatment is still being tested on a research basis. [fcdgc.rarediseasesnetwork.org]

What is the prognosis for a person with Congenital Disorder of Glycosylation Type Ia? Twenty percent of people with CDG-Ia die within the first year of life, often due to infection, liver problems, or heart disease. [myriad.com]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

Prognosis for Congenital Disorders of Glycosylation PMM2-CDG (CDG-Ia) Glycomine, a research lab in the USA, is researching how to transport the PMM2 enzyme through the cell membrane and into the cell as a therapeutic treatment. [cdg-uk.org]

Details about these treatments are under the “Targeted Therapies and Prognosis” section below. [atm.amegroups.com]

Clinical features and genetic etiology of more common CDG by pathway is summarized in Table S1. [atm.amegroups.com]

Epidemiology The incidence and prevalence of all types of CDG in aggregate have not been well established, although patients have been reported worldwide from almost every ethnic background and both sexes are equally affected. [atm.amegroups.com]

Although the pathophysiology of multitude symptoms remains to be elucidated, the relationship between certain glycosylation pathways and specific clinical symptoms has been clarified. [atm.amegroups.com]

All of the symptoms do not fully recover on this therapy, therefore the rest of the treatment focuses on identifying treatable medical conditions and preventing complications, (including supportive heart treatment, physical therapy, occupational therapy [fcdgc.rarediseasesnetwork.org]

Health concerns can be decreased through preventative medicine with appropriate nutrition and scheduled immunizations. Doctors and scientists are working to find and create more specific treatments for CDG. CDG CARE supports these research efforts. [cdgcare.org]

In gene therapy, the defective gene present in a patient is replaced with a normal gene to enable the production of the active enzyme and prevent the development and progression of the disease. [rarediseases.org]

For example, N-acetylgalactosaminyltransferase 3 (GALNT3) O-glycosylates the phosphaturic hormone, FGF23, preventing proteolytic cleavage and allowing its intact secretion. [atm.amegroups.com]