Klinische FragestellungKongenitale Störungen der Glykosylierung, CDG; Differentialdiagnose

NGS +

Kongenitale Störungen der Glykosylierung (CDGs) ist ein Überbegriff für eine schnell wachsende Gruppe von >60 seltenen genetischen Stoffwechselstörungen, die auf Defekten bei der komplexen Glykosylierung beruht. Die verschiedenen Entitäten dieser Defekt-Gruppe werden je nach betroffenem Syntheseweg in Störungen der Protein-N-Glykosylierung, Störungen der Protein-O-Glykosylierung, Störungen der Mehrfach-Glykosylierung und Störungen der Glykosphingolipid- und Glykosylphosphatidylinositol-Ankerglykosylierung unterteilt. An diesen Glykosylierungsprozessen sind viele verschiedene Gene beteiligt. Ein Mangel oder das Fehlen eines dieser Enzyme kann zu einer Vielzahl von Symptomen führen, die möglicherweise mehrere Organsysteme betreffen. CDGs können jeden Körperteil betreffen, und fast immer gibt es wichtige neurologische Mitbeteiligungen. CDGs können mit einer Vielzahl von Symptomen einhergehen und in ihrem Schweregrad von leichten Beeinträchtigungen bis hin zu schweren, behindernden oder lebensbedrohlichen Fällen variieren. Symptome der CDGs zeigen sich meist schon im Kindesalter. Die Mutationsfrequenzen in den betreffenden CDG-Genen unterscheiden sich z.T. ganz erheblich zwischen verschiedenen Populationen. Die meisten CDGs werden autosomal rezessiv vererbt. Die DNA-diagnostische Ausbeute übertrifft insgesamt kaum 30-40%. Damit stellt ein negatives molekulargenetisches Ergebnis keinen Ausschluss der klinischen Diagnose dar.

Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1332/

https://www.ncbi.nlm.nih.gov/books/NBK1110/

https://www.ncbi.nlm.nih.gov/books/NBK5200/

https://www.ncbi.nlm.nih.gov/books/NBK481554/

• Allelic: Cardiomyopathy, dilated, 1X (FKTN)
• Allelic: Chondrosarcoma (EXT1)
• Allelic: Cowden syndrome 7 (SEC23B)
• Allelic: Polycystic liver disease 3 with/-out kidney cysts (ALG8)
• Allelic: Pseudoxanthoma elasticum, modifier of severity of (XYLT1, XYLT2)
• Allelic: Retinitis pigmentosa 59 (DHDDS)
• Allelic: Retinitis pigmentosa 76 (POMGNT1)
• Adams-Oliver syndrome 4 (EOGT)
• Al-Gazali syndrome (B3GALT6)
• Alacrima, achalasia, and mental retardation syndrome (GMPPA)
• CHIME (Coloboma, cong. Heart defects, Ichthyosif. Migrat. dermatosis, ID, Ear anom.) syndrome (PIGL)
• Congenital disorder of deglycosylation (NGLY1)
• Congenital disorder of glycosylation [panelapp] (SSR3)
• Congenital disorder of glycosylation with defective fucosylation 1 (FUT8)
• Congenital disorder of glycosylation with defective fucosylation 2 (FCSK syn. FUK)
• Congenital disorder of glycosylation, type IIa (MGAT2)
• Congenital disorder of glycosylation, type IIb (MOGS)
• Congenital disorder of glycosylation, type IIc (SLC35C1)
• Congenital disorder of glycosylation, type IId (B4GALT1)
• Congenital disorder of glycosylation, type IIe (COG7)
• Congenital disorder of glycosylation, type IIf (SLC35A1)
• Congenital disorder of glycosylation, type IIg (COG1)
• Congenital disorder of glycosylation, type IIh (COG8)
• Congenital disorder of glycosylation, type IIi (COG5)
• Congenital disorder of glycosylation, type IIj (COG4)
• Congenital disorder of glycosylation, type IIk (TMEM165)
• Congenital disorder of glycosylation, type IIl (COG6)
• Congenital disorder of glycosylation, type IIm (SLC35A2)
• Congenital disorder of glycosylation, type IIn (SLC39A8)
• Congenital disorder of glycosylation, type IIo (CCDC115)
• Congenital disorder of glycosylation, type IIp (TMEM199)
• Congenital disorder of glycosylation, type IIq (COG2)
• Congenital disorder of glycosylation, type IIt (GALNT2)
• Congenital disorder of glycosylation, type IIv (EDEM3)
• Congenital disorder of glycosylation, type IIw (SLC37A4)
• Congenital disorder of glycosylation, type Ia (PMM2)
• Congenital disorder of glycosylation, type Ibb (DHDDS)
• Congenital disorder of glycosylation, type Ic (ALG6)
• Congenital disorder of glycosylation, type Icc (MAGT1)
• Congenital disorder of glycosylation, type Id (ALG3)
• Congenital disorder of glycosylation, type Ie (DPM1)
• Congenital disorder of glycosylation, type Ie (MPI)
• Congenital disorder of glycosylation, type If (MPDU1)
• Congenital disorder of glycosylation, type Ig (ALG12)
• Congenital disorder of glycosylation, type Ih (ALG8)
• Congenital disorder of glycosylation, type Ii (ALG2)
• Congenital disorder of glycosylation, type Ij (DPAGT1)
• Congenital disorder of glycosylation, type Ik (ALG1)
• Congenital disorder of glycosylation, type Il (ALG9)
• Congenital disorder of glycosylation, type Im (DOLK)
• Congenital disorder of glycosylation, type In (RFT1)
• Congenital disorder of glycosylation, type Ip (ALG11)
• Congenital disorder of glycosylation, type Iq (SRD5A3)
• Congenital disorder of glycosylation, type Ir (DDOST)
• Congenital disorder of glycosylation, type Is (ALG13)
• Congenital disorder of glycosylation, type It (PGM1)
• Congenital disorder of glycosylation, type Iu (DPM2)
• Congenital disorder of glycosylation, type Iw (STT3A)
• Congenital disorder of glycosylation, type Ix (STT3B)
• Congenital disorder of glycosylation, type Iy (SSR4)
• Cutis laxa, Ar, type IIA (ATP6V0A2)
• Desbuquois dysplasia 2 (XYLT1)
• Developmental + epileptic encephalopathy 15 (ST3GAL3)
• Developmental + epileptic encephalopathy 36 (ALG13)
• Developmental + epileptic encephalopathy 50 (CAD)
• Developmental + epileptic encephalopathy 95 (PIGS)
• Developmental delay + seizures with/-out movement abnormalities (DHDDS)
• Dursun syndrome (G6PC3)
• Dyserythropoietic anemia, congenital, type II (SEC23B)
• Ehlers-Danlos syndrome, musculocontractural type 1 (CHST14)
• Ehlers-Danlos syndrome, spondylodysplastic type, 1 (B4GALT7)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (B3GALT6)
• Exostoses, multiple, type 1 (EXT1)
• Exostoses, multiple, type 2 (EXT2)
• Geroderma osteodysplasticum (GORAB)
• Gillessen-Kaesbach-Nishimura syndrome (ALG9)
• Glycogen storage disease Ib (SLC37A4)
• Glycogen storage disease Ic (SLC37A4)
• Glycosylphosphatidylinositol biosynthesis defect 11 (PIGW)
• Glycosylphosphatidylinositol deficiency (PIGM)
• Hyperphosphatasia with mental retardation syndrome 1 (PIGV)
• Hyperphosphatasia with mental retardation syndrome 2 (PIGO)
• Hyperphosphatasia with mental retardation syndrome 3 (PGAP2)
• Hyperphosphatasia with mental retardation syndrome 4 (PGAP3)
• Immunodeficiency 23 (PGM3)
• Immunodeficiency 47 (ATP6AP1)
• Immunodeficiency, XL, with magnesium defect, Epstein-Barr virus infection + neoplasia (MAGT1)
• Intellectual developmental disorder + epilepsy, behavioral abnormalities + coarse facies (ALG14)
• Intellectual developmental disorder, AR 12 (ST3GAL3)
• Kahrizi syndrome (SRD5A3)
• Mental retardation, AR 7 (TUSC3)
• Multiple congenital anomalies-hypotonia-seizures syndrome 1 (PIGN)
• Multiple congenital anomalies-hypotonia-seizures syndrome 2 (PIGA)
• Multiple congenital anomalies-hypotonia-seizures syndrome 3 (PIGT)
• Multiple joint disloc., short stature, craniofacial dysmorph. with/-out cong. heart defects (B3GAT3)
• Muscular dystrophy, limb-girdle, AR 18 (TRAPPC11)
• Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies, type A, 8 (POMGNT2)
• Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 10 (TMEM5/RXYLT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 11 (B3GALNT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. with impaired intellectual devel., type B, 15 (DPM3)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with/-out mental retardation, type B, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. without mental retardation, type B, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 15 (DPM3)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 8 (POMGNT2)
• Myasthenia, congenital, 12, with tubular aggregates (GFPT1)
• Myasthenic syndrome, congenital, 13, with tubular aggregates (DPAGT1)
• Myasthenic syndrome, congenital, 14, with tubular aggregates (ALG2)
• Myasthenic syndrome, congenital, 15, without tubular aggregates (ALG14)
• Myopathy, epilepsy + progressive cerebral atrophy (ALG14)
• Neutropenia, severe congenital 4, AR (G6PC3)
• Nonaka myopathy (GNE)
• Paroxysmal nocturnal hemoglobinuria 2 (PIGT)
• Paroxysmal nocturnal hemoglobinuria, somatic (PIGA)
• Peters-plus syndrome (B3GLCT)
• Rafiq syndrome (MAN1B1)
• Salt and pepper developmental regression syndrome (ST3GAL5)
• Saul-Wilson syndrome (COG4)
• Seizures, scoliosis + macrocephaly syndrome (EXT2)
• Shaheen syndrome (COG6)
• Sialuria (GNE)
• Skeletal dysplasia, mild, with joint laxity + advanced bone age (CSGALNACT1)
• Spastic paraplegia 26, AR (B4GALNT1)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with/-out fractures (B3GALT6)
• Spondyloepiphyseal dysplasia with congenital joint dislocations (CHST3)
• Spondyloocular syndrome (XYLT2)
• Temtamy preaxial brachydactyly syndrome (CHSY1)
• Tumoral calcinosis, hyperphosphatemic, familial, 1 (GALNT3)
• Wrinkly skin syndrome (ATP6V0A2)