Am J Hum Genet 94:161–175 CAS Article PubMed PubMed Central Google Scholar Fung CW, Matthijs G, Sturiale L et al (2012) COG5-CDG with a mild neurohepatic presentation. [link.springer.com]

Individuals who are only mildly affected may present with isolated developmental delay, intellectual disability and coagulation abnormalities. [fcdgc.rarediseasesnetwork.org]

O-linked CDGs, in contrast, typically present as muscular dystrophies with additional phenotypes such as hypotonia, brain malformations, intellectual disability, cardiac involvement, or ocular dysfunction (Martin. 2005. PubMed ID: 16584074). [preventiongenetics.com]

Case Presentation A 23-year-old third gravida lady was referred at 19-week gestation for genetic counseling for having a previous 3-year-old male child with short stature and developmental delay. [hindawi.com]

In this issue Table of Contents Jump to section Article Abstract Education Gaps Objectives Introduction Classification Nomenclature Clinical Presentation Diagnosis Management Conclusions Footnotes Suggested Reading Info & Metrics Comments Related Articles [neoreviews.aappublications.org]

• Developmental Delay

  Individuals who are only mildly affected may present with isolated developmental delay, intellectual disability and coagulation abnormalities. [fcdgc.rarediseasesnetwork.org]

  Genes related to Alg12-cdg ALG12 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Alg12-cdg Seizures Global developmental delay Generalized hypotonia Hearing impairment Microcephaly Failure to thrive [mendelian.co]

  delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. [findexpertmd.com]

  Cardiomyopathy, dilated, 1GG neonatal isolated Carnitine deficiency, systemic primary Carnitine palmitoyltransferase 1 deficiency Carnitine-acylcarnitine translocase deficiency – CACT Cerebellar ataxia and developmental delay Cerebral creatine deficiency [zerlaboratories.com]

• Feeding Difficulties

  Congenital disorder of glycosylation type 1G: A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe [findexpertmd.com]

  Orpha Number: 79324 Definition A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental [rareguru.com]

  Feeding difficulties can lead to a failure to gain weight and grow slower than normal (failure to thrive). Ocular abnormalities, sensorineural hearing loss, cardiac abnormalities and skeletal dysplasias are possible. [fcdgc.rarediseasesnetwork.org]

  difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. [mendelian.co]

  They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). [ncbi.nlm.nih.gov]

• Epilepsy

  progressive myoclonic 1B Epilepsy, progressive myoclonic 2A (Lafora) Epilepsy, pyridoxine-dependent Epileptic encephalopathy, early infantile, 18 Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE Exfoliative ichthyosis [zerlaboratories.com]

  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]

  Factor II deficiency F2 Ehlers-Danlos syndrome, type VI PLOD1 Ellis-van Creveld Syndrome EVC2 Emphysema due to Alpha1 Anti-Trypsin deficiency SERPINA1 Epidermolysis bullosa dystrophica, AR COL7A1 Epidermolysis bullosa, junctional, Herlitz type LAMB3 Epilepsy [ceifer.com]

  Pediatrics 130:e1034–e1039 Article PubMed Google Scholar Morava E, Tiemes V, Thiel C et al (2016) ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavior and limb anomalies. [link.springer.com]

  […] of glycosylation CDHS, see Craniofacial-deafness-hand syndrome CDKL5 deficiency, see CDKL5 deficiency disorder CDKL5 deficiency disorder CDKL5 disorder, see CDKL5 deficiency disorder CDKL5 encephalopathy, see CDKL5 deficiency disorder CDKL5-related epilepsy [medlineplus.gov]

• Recurrent Infection

  infection syndrome, autosomal recessive Hyperinsulinemic hypoglycemia, familial, 1 (PHHI/HHF1) Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome Hyperoxaluria, primary, type I Hyperoxaluria, primary, type II Hyperoxaluria, primary, type III [zerlaboratories.com]

  Fucose therapy can be beneficial in treating recurrent infections associated with this form of CDG and improving health. However, fucose therapy does not help with other symptoms of this disorder. [rarediseases.org]

• Failure to Thrive

  Feeding difficulties can lead to a failure to gain weight and grow slower than normal (failure to thrive). Ocular abnormalities, sensorineural hearing loss, cardiac abnormalities and skeletal dysplasias are possible. [fcdgc.rarediseasesnetwork.org]

  Failure to thrive MedGen UID: 746019 •Concept ID: C2315100 • Disease or Syndrome Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. [ncbi.nlm.nih.gov]

  Genes related to Alg12-cdg ALG12 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Alg12-cdg Seizures Global developmental delay Generalized hypotonia Hearing impairment Microcephaly Failure to thrive [mendelian.co]

  They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). [malacards.org]

  The majority of N-linked CDGs present in infancy, and symptoms may include failure to thrive, developmental delay, liver dysfunction, seizures, hypotonia, hypoglycemia, protein-losing enteropathy, eye dysfunction (such as strabismus or retinitis pigmentosa [preventiongenetics.com]

• Vomiting

  […] syndrome Cyclic hematopoesis, see Cyclic neutropenia Cyclic leucopenia, see Cyclic neutropenia Cyclic neutropenia Cyclic vomiting syndrome Cyclical vomiting, see Cyclic vomiting syndrome Cyclical vomiting syndrome, see Cyclic vomiting syndrome CYLD cutaneous [medlineplus.gov]

  Many children with a CDG develop persistent vomiting and dysfunction of oral motor skills, which involve the muscles of the face and throat. [rarediseases.org]

  Soon in infancy, cyclic episodes of vomiting and/or diarrhea with threatening dehydration were frequent and often urgent reasons for hospitalization. [nature.com]

• Small Head

  In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures.Some people with ALG12-CDG have physical abnormalities such as a small head size (microcephaly) and [ncbi.nlm.nih.gov]

• Osteoporosis

  see Juvenile primary osteoporosis CHMP2B-related frontotemporal dementia CHMRQ1, see VLDLR-associated cerebellar hypoplasia Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, see Burn-McKeown syndrome Cholangiocarcinoma [medlineplus.gov]

  TCIRG1 Osteoporosis: Relacionada con TCIRG1 AR DESCRIPCIÓN Osteoporosis: Relacionada con TCIRG1: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson ad squid. [genaden.com]

• Hearing Impairment

  Sensorineural hearing impairment Abnormal facial shape Muscular hypotonia Cognitive impairment And another 35 symptoms. [mendelian.co]

  Sensorineural hearing loss MedGen UID: 9164 •Concept ID: C0018784 • Disease or Syndrome A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. [ncbi.nlm.nih.gov]

• Seizure

  Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. ALG12-CDG is caused by loss of function mutations of the gene ALG12 (22q13.33). [mendelian.co]

  Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. The disease is caused by loss of function mutations of the gene ALG12 (22q13.33). [findexpertmd.com]

  Symptoms manifest during infancy or early childhood, including failure to thrive, decreased muscle tone, developmental delay, intellectual disability, seizures, skeletal abnormalities, unusual facial features, sensorineural hearing loss (hearing loss [fcdgc.rarediseasesnetwork.org]

  For example, anti-seizure medications (anti-convulsants) may be used to treat seizures, thyroid hormone may be used to treat hypothyroidism and surgery may be used to treat certain skeletal malformations. [rarediseases.org]

• Convulsions

  For example, anti-seizure medications (anti-convulsants) may be used to treat seizures, thyroid hormone may be used to treat hypothyroidism and surgery may be used to treat certain skeletal malformations. [rarediseases.org]

  The recurrent episodes in infancy and early childhood may be associated with convulsions, apnea, decreased consciousness or coma. Patients may have generalized edema. [nature.com]

Treatment and Prognosis To date, there are no known specific treatment options for ALG12-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. [fcdgc.rarediseasesnetwork.org]

At this time, treatment is available for MPI-CDG (oral mannose or liver transplantation) (Jaeken. 2017. PubMed ID: 28484880). [preventiongenetics.com]

Standard Therapies Treatment The treatment of most forms of CDG is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

In: Saudubray, Baumgartner, Walter (ed) Inborn metabolic diseases. diagnosis and treatment, 6th edn. [link.springer.com]

Early diagnosis is important, because treatment options are available for some subtypes. Copyright © 2017 by the American Academy of Pediatrics Individual Login Log in You will be redirected to aap.org to login or to create your account. [neoreviews.aappublications.org]

Treatment and Prognosis To date, there are no known specific treatment options for ALG12-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. [fcdgc.rarediseasesnetwork.org]

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

Presence of congenital heart defects, genitourinary anomalies such as hydronephrosis, hypospadias, cryptorchidism, hypoplastic clitoris, and labia majora, and structural brain malformations may alter the prognosis [2]. [hindawi.com]

Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. Mild cases, however, seem to have a good life expectancy. [fcdgc.rarediseasesnetwork.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]

Hence, early specific diagnosis of any one entity is crucial for genetic counseling and elective preventive measures. [nature.com]