Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih

Stölting, Torsten; Omran, Heymut; Erlekotte, Anne; Denecke, Jonas; Marquardt, Thorsten

doi:10.1016/j.ymgme.2009.06.010

Cited by 20 publications

(15 citation statements)

References 10 publications

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“…PMM2‐CDG is the most frequent CDG. Other forms of CDG found in our review include ALG8‐CDG (OMIM#608104), caused by the deficiency of glucosyltransferase II, ALG1‐CDG (OMIM #608540) caused by the deficiency of mannosyltransferase I, ALG9‐CDG (OMIM #608776) caused by deficiency of an α‐1,2‐mannosyltransferase, MGAT2‐CDG caused by N‐acetylglucosaminyltransferase II deficiency, and COG6‐CDG (OMIM #606977), caused by a deficiency in the conserved oligomeric Golgi (COG) complex subunit 6, which plays a key role in protein transport between endoplasmic reticulum and Golgi and within the Golgi …”

Section: Discussionmentioning

confidence: 89%

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

Makhamreh

Cottingham

Ferreira

et al. 2019

J of Inher Metab Disea

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Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This study reviews prenatal and neonatal characteristics of CDG presenting with NIHF. A systematic literature search was performed. Thirteen articles met the inclusion criteria. Twenty‐one cases with NIHF associated with a CDG were reported. There were 17 live births, three pregnancy terminations, and one fetal demise. Timing of CDG diagnosis was reported mostly postnatally (90%; 10/11). Postnatal genetic testing was reported in 18 patients; three patients were diagnosed by isoelectric focusing of serum transferrin that showed a type 1 pattern. The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15). In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11), and 38% (8/21) reported cardiovascular abnormalities, most commonly hypertrophic cardiomyopathy (63%; 5/8). Among live births, 71% (12/17) infants died at a median age of 34 days (range 1‐185). Thrombocytopenia was reported in 53% (9/17) patients. Of those who survived past the neonatal period, 80% (4/5) had significant reported developmental delays. CDG should be on the differential diagnosis of NIHF in the presence of cerebellar atrophy, hypertrophic cardiomyopathy, or thrombocytopenia. Our review highlights the poor prognosis in infants with NIHF due to CDG and demonstrates the importance of identifying these disorders prenatally to guide providers in their counseling with families regarding pregnancy management. Synopsis Poor prognosis in fetuses and infants with nonimmune hydrops fetalis due to congenital disorders of glycosylation highlights the importance of prenatal diagnosis of this disorder.

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Section: Discussionmentioning

confidence: 89%

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

Makhamreh

Cottingham

Ferreira

et al. 2019

J of Inher Metab Disea

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“…ALG12‐CDG (CDG‐Ig) is unique because affected individuals have immunodeficiency [Eklund , Kranz et al, ]. A number of other multi‐system findings are also described in a few patients in various CDG (Tables and ), with findings including sensorineural deafness, microcephaly, inverted nipples, coagulopathy, kyphoscoliosis, liver disease and protein‐wasting enteropathy , significant visual impairment , hyperinsulinemic hypoglycemia and multi‐organ system involvement [Rind, ; Frank, ; Schollen, ; Kranz et al, ; Stölting, ; Clayton and Grunewald, ; Jaeken, ].…”

Section: Introductionmentioning

confidence: 99%

Congenital disorders of glycosylation and intellectual disability

Wolfe

Krasnewich

2013

Dev Disabil Res Revs

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The congenital disorders of glycosylation (CDG) are a rapidly growing group of inborn errors of metabolism that result from defects in the synthesis of glycans. Glycosylation is a major post-translational protein modification and an estimated 2% of the human genome encodes proteins for glycosylation. The molecular bases for the current 60 disorders, affecting approximately 800 individuals, have been identified, many in the last 5 years. CDG should be considered in any multi-system syndrome or single tissue disorder not explained by the identification of another disorder. The initial clinical presentation varies significantly among individuals, even between affected siblings. However, two thirds of the known CDGs are associated with intellectual disabilities and most affected individuals need support services throughout their lives. Additional disorders of glycosylation are likely to be characterized over time.

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“…Neurological manifestations are variable but usually include severe psychomotor disability, seizures and hypotonia . Unsteady ataxic gait with normal brain and cerebellar imaging was described in two siblings with a mild ALG8‐CDG phenotype . About half of 15 ALG8‐CDG patients reported so far died precociously .…”

Section: Discussionmentioning

confidence: 99%

Hyperkinetic movement disorders in congenital disorders of glycosylation

Mostile

Barone

Rizzo

et al. 2019

Euro J of Neurology

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Background and purpose Congenital disorders of glycosylation (CDG) represent an increasing number of rare inherited metabolic diseases associated with abnormal glycan metabolism and disease onset in infancy or early childhood. Most CDG are multisystemic diseases mainly affecting the central nervous system. The aim of the current study was to investigate hyperkinetic movement disorders in patients affected by CDG and to characterize phenomenology based on CDG subtypes. Methods Subjects were identified from a cohort of patients with CDG who were referred to the University Hospital of Catania, Italy. Patients were evaluated by neurologists with expertise in movement disorders and videotaped using a standardized protocol. Results A variety of hyperkinetic movement disorders was detected in eight unrelated CDG patients. Involuntary movements were generally observed early in childhood, maintaining a clinical stability over time. Distribution ranged from a generalized, especially in younger subjects, to a segmental/multifocal involvement. In patients with phosphomannomutase 2 CDG, the principal movement disorders included dystonia and choreo‐athetosis. In patients affected by other CDG types, the movement disorders ranged from pure generalized chorea to mixed movement disorders including dystonia and complex stereotypies. Conclusions Hyperkinetic movement disorder is a key clinical feature in patients with CDG. CDG should be considered in the differential diagnosis of childhood‐onset dyskinesia, especially when associated with ataxia, developmental delay, intellectual disability, autism or seizure disorder.

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Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih

Cited by 20 publications

References 10 publications

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

Congenital disorders of glycosylation and intellectual disability

Hyperkinetic movement disorders in congenital disorders of glycosylation

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