Known Human Glycosylation Disorders

Dirk Lefeber; Hudson H. Freeze; Richard Steet; Taroh Kinoshita

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Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology [Internet]. 4th edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2022.

Essentials of Glycobiology [Internet]. 4th edition.

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Online Appendix 45AKnown Human Glycosylation Disorders

Dirk Lefeber, Hudson H. Freeze, Richard Steet, and Taroh Kinoshita.

Author Information and Affiliations

Table 1

Disorder	Gene	Function	Disorder OMIM	Gene OMIM	Main clinical features	Year	Reference
N-linked pathway
DPAGT1–CDG	DPAGT1	GlcNAc-1-P transferase	608093	191350	ID, Hy, Sz, M, infections, early death, CMS	2003	PMID: 12872255
ALG1–CDG	ALG1	β1-4 mannosyltransferase	608540	605907	ID, Hy, Sz, M, infections, early death	2004	PMID: 14709599 PMID: 14973778 PMID: 14973782
ALG2–CDG	ALG2	α1-3 mannosyltransferase	607906	607905	ID, Hy, Sz, infections, hypomyelination, hepatomegaly, early death	2003	PMID: 12684507
ALG2–CMS	ALG2	α1-3 mannosyltransferase	607906	607905	CMS	2013	PMID: 23404334
ALG3–CDG	ALG3	α1-3 mannosyltransferase	601110	608750	ID, Hy, Sz, M, optic nerve atrophy	1999	PMID: 10581255
ALG6–CDG	ALG6	α1-3 glucosyltransferase	603147	604566	ID, Hy, Sz, M, ataxia	1999	PMID: 10359825
ALG8–CDG	ALG8	α1-3 glucosyltransferase	608104	608103	DD, hepatomegaly, protein-losing enteropathy, coagulopathy, ascites, renal failure, early death	2003	PMID: 12480927
ALG9–CDG	ALG9	α1-2 mannosyltransferase	608776	606941	ID, Hy, Sz, hepatomegaly	2004	PMID: 15148656
ALG10–CDG	ALG10	α1,2-Glucosyltransferase	N/A	618355	Progressive myoclonus epilepsy	2021	PMID: 33798445
ALG11–CDG	ALG11	α1-2 mannosyltransferase	613661	613666	ID, Hy, Sz, deafness, dysmorphism	2010	PMID: 20080937
ALG12–CDG	ALG12	α1-6 mannosyltransferase	607143	607144	ID, Hy, Sz, M, recurrent infections	2002	PMID: 11983712 PMID: 12217961
ALG13–CDG	ALG13	UDP-GlcNAc transferase	300884	300776	M, Sz, hepatomegaly, horizontal nystagmus, optic nerve atrophy, infections	2012	PMID: 22492991
ALG14-CMS	ALG14	UDP-GlcNAc transferase	616227	612866	CMS	2013	PMID: 23404334
ALG14–CDG	ALG14	UDP-GlcNAc transferase	619031 619036	612866	epilepsy, cerebral atrophy	2017	PMID: 28733338
RFT1–CDG	RFT1	Man5GlcNAc2 flippase	612015	611908	ID, Hy, Sz, M, hepatomegaly, coagulopathy, deafness	2008	PMID: 18313027
STT3A–CDG (recessive)	STT3A	subunit of the OST complex	615596	601134	ID, DD, H, M, Sz, failure to thrive	2013	PMID: 23842455
STT3A-CDG (dominant)	STT3A	subunit of the OST complex	615596	601134	Variable skeletal anomalies, short stature, dysmorphic features, ID, and increased muscle tone and muscle cramps.	2021	PMID: 34653363
STT3B–CDG	STT3B	subunit of the OST complex	615597	608605	ID, DD, H, M, Sz, failure to thrive, thrombocytopenia, genital abnormalities	2013	PMID: 23842455
MAGT1–CDG	MAGT1	subunit of the OST complex	300716	300715	XLNSID	2008	PMID: 18455129
TUSC3–CDG	TUSC3	subunit of the OST complex	611093	601385	NSID	2008	PMID: 18452889 PMID: 18455129
DDOST–CDG	DDOST	subunit of the OST complex	614507	602202	ID, DD, failure to thrive, gastroesophageal reflux, ear infections, oromotor dysfunction	2012	PMID: 22305527
OSTc–CDG	OSTc	subunit of the OST complex	N/A	619023	M, dysmorphic facies, congenital heart defect, focal epilepsy, IS, skeletal dysplasia and was fatal.	2020	PMID: 32267060
TREX-CDG	TREX1	OST chaperone	225750 610448 192315 152700	606609	autoimmune and autoinflammatory diseases	2015	PMID: 26320659
NGLY1–CDG	NGLY1	N-glycanase-1	615273	610661	ID, DD, Sz, abnormal liver function	2012	PMID: 22581936
MAN2C1-CDG	MAN2C1	free oligosaccharide processing	N/A	154580	ID, brain abnormalities, dysmorphic facies	2021	https://doi.org/10.1016/j.ajhg.2021.12.010
SSR3–CDG	SSR3	signal sequence receptor, gamma	N/A	606213	Sz, ID, DD, M, abnormal brain structure	2019	PMID: 30945312
SSR4–CDG	SSR4	signal sequence receptor, delta	300934	300090	M, ID, Sz, gastroesophageal reflux	2013	PMID: 24218363
MGAT2–CDG	MGAT2	GlcNAc-transferase II	212066	602616	ID, feeding problems, severe diarrhea, growth retardation, dysmorphism	1996	PMID: 8808595
MOGS–CDG	MOGS	α1-2 glucosidase	606056	601336	Hy, Sz, hepatomegaly, hypoventilation, feeding problems, dysmorphism, fatal, unique tetrasaccharide in urine	2000	PMID: 10788335
Autosomal-Dominant Polycystic Kidney and Liver Disease	GANAB	α1-3 glucosidase	600666	104160	autosomal-dominant polycystic kidney and liver disease	2016	PMID: 27259053
MAN1B1–CDG	MAN1B1	α1-2 mannosidase	614202	604346	NSID, delayed motor and speech development, variable dysmorphic features, truncal obesity, macrocephaly	2011	PMID: 21763484
I-cell disease	GNPTAB	GlcNAc-1-P transferase	252500 252600	607840	ID, congenital dislocation of the hip, thoracic deformities, hernia, hyperplastic gums, coarse facial features, restricted joint movement	1981	PMID: 6461005
Autosomal-dominant polycystic liver disease	PRKCSH	glucosidase II subunit β	174050	177060	autosomal-dominant polycystic liver disease	2003	PMID: 12529853 PMID: 12577059
Congenital severe neutropenia	JAGN1	endoplasmic reticulum organization	616022	616012	congenital severe neutropenia, recurrent infections	2014	PMID: 25129144 PMID: 25129145
FUT8-CDG	FUT8	α1-6 fucosyltransferase	618005	602589	Severe DD, growth retardation, feeding problems, short stature, respiratory difficulties	2017	PMID: 29304374
MAN2A2-CDG	MAN2A2	Golgi Alpha-Mannosidase II	N/A	600988	ID, DD		*
EDEM3-CDG	EDEM3	ER Degradation Enhancing Alpha-Mannosidase Like Protein 3	619493	610214	Neurodevelopmental delay and variable facial dysmorphisms	2021	PMID: 34143952
Potential to effect multiple pathways
PMM2–CDG	PMM2	conversion of Man-6-P to Man-1-P	212065	601785	ID, Hy, Sz, strabismus, cerebellar hypoplasia, failure to thrive, cardiomyopathy, 20% lethality in the first 5 yr	1997	PMID: 9140401
MPI–CDG	MPI	conversion of Fruct-6-P and Man-6-P	602579	154550	Hepatic fibrosis, coagulopathy, hypoglycemia, protein-losing enteropathy, vomiting, no neurological symptoms	1998	PMID: 9525984
DHDDS–CDG (recessive)	DHDDS	dehydrodolichol diphosphate synthase	613861	608172	Retinitis pigmentosa in Ashkenazi Jews	2011	PMID: 21295282 PMID: 21295283
DHDDS-CDG (dominant)	DHDDS	dehydrodolichol diphosphate synthase	617836	608172	DD, Sz, neurodegeneration	2021	PMID: 34382076
NUS1–CDG (recessive)	NUS1	dehydrodolichol diphosphate synthase	617082	610463	DD, ID, Sz, Hy	2014	PMID: 25066056
MRD55 (dominant)	NUS1	dehydrodolichol diphosphate synthase	617831	610463	Mental retardation, autosomal dominant 55, with seizures	2017	PMID: 29100083
DOLK–CDG	DOLK	Dol kinase	610768	610746	ID, Hy, Sz, hypoglycemia, ichthyosis, dilated cardiomyopathy, cardiac failure	2007	PMID: 17273964
SRD5A3–CDG	SRD5A3	polyprenol reductase	612379	611715	ID, Hy, eye and brain malformations, nystagmus, hepatic dysfunction, coagulopathy, ichthyosis	2010	PMID: 20637498
DPM1–CDG	DPM1	Dol-P-Man synthase complex	608799	603503	ID, Hy, Sz, M, dysmorphism, coagulopathy	2000	PMID: 10642597 PMID: 10642602
DPM2–CDG	DPM2	Dol-P-Man synthase complex	615042	603564	dystroglycanopathy, Sz, Hy, M, dysmorphism, cerebellar hypoplasia, early death	2012	PMID: 23109149
DPM3–CDG	DPM3	Dol-P-Man synthase complex	612937	605951	dystroglycanopathy, dilated cardiomyopathy, stroke-like episode	2009	PMID: 19576565
MPDU1–CDG	MPDU1	Man-P-Dol utilization	609180	604041	ID, Sz, failure to thrive, ichthyosis-like skin disorder, severe feeding difficulties	2001	PMID: 11733556 PMID: 11733564
FCSK-CDG	FCSK	Fucose Kinase	618324	608675	severe DD, encephalopathy, intractable Sz, and Hy	2018	PMID: 30503518
GFUS-CDG	GFUS	GDP-L-fucose synthase	N/A	137020	DD, mild coarse facial features	2021	PMID: 34468083
GMPPA–CDG	GMPPA	GDP-Man pyrophosphorylase A	615510	615495	achalasia, alacrima, neurological deficits	2013	PMID: 24035193
B4GALT1–CDG	B4GALT1	β1-4 galactosyltransferase	607091	137060	ID, DD, Hy, macrocephaly, Dandy–Walker malformation, coagulopathy, myopathy	2002	PMID: 11901181
SLC35A1–CDG	SLC35A1	CMP-sialic acid transporter	603585	605634	ID, Sz, ataxia, bleeding, thrombocytopenia, neutropenia, renal and cardiac involvement	2005 2013	PMID: 15576474 PMID: 23873973
SLC35A2–CDG	SLC35A2	UDP-Gal transporter	300896	314375	ID, Sz, skeletal anomalies	2013	PMID: 23561849
SLC35A3–CDG	SLC35A3	UDP-GlcNAc transporter	615553	605632	autism spectrum disorder, Hy, epilepsy, arthrogryposis	2013	PMID: 24031089
SLC39A8–CDG	SLC39A8	manganese transporter	616721	608732	cranial asymmetry, severe infantile spasms with hypsarrhythmia, dysproportionate dwarfism	2015	PMID: 26637979 PMID: 26637978
SLC35C1–CDG	SLC35C1	GDP-Fuc transporter	266265	605881	ID, Hy, Sz, M, unusual facial appearance, dwarfism, infections with neutrophilia	2001	PMID: 11326279
COG1–CDG	COG1	Golgi-to-ER retrograde transport	611209	606973	ID, shortened long bones, facial dysmorphism	2006	PMID: 16537452
COG1–CCMS	COG1	Golgi-to-ER retrograde transport	611209	606973	CCMS	2009	PMID: 19008299
COG2–CDG	COG2	Golgi-to-ER retrograde transport	617395	606974	M, psychomotor retardation, Sz, liver dysfunction, hypocupremia, hypoceruloplasminemia	2014	PMID: 24784932
COG3–CDG	COG3	Golgi-to-ER retrograde transport	N/A	606975	severe DD, Hy, cerebral and cerebellar atrophy	2021	*
COG4–CDG (recessive)	COG4	Golgi-to-ER retrograde transport	613489	606976	DD, Hy, Sz, nystagmus, hepatosplenomegaly, failure to thrive in infancy with recurrent diarrhea, early death	2009	PMID: 19494034
Saul-Wilson syndrome (dominant)	COG4	Golgi-to-ER retrograde transport	613489	606976	dwarfism, DD, characteristic facial and radiographic features	2018	PMID: 30290151
COG5–CDG	COG5	Golgi-to-ER retrograde transport	613612	606821	ID, Hy, delayed speech, ataxia	2009	PMID: 19690088
COG6–CDG	COG6	Golgi-to-ER retrograde transport	614576	606977	severe neurologic disorder, Sz, vomiting	2010	PMID: 20605848
COG7–CDG	COG7	Golgi-to-ER retrograde transport	608779	606978	Hy, M, growth retardation, adducted thumbs, failure to thrive, cardiac anomalies, wrinkled skin, early death	2004	PMID: 15107842
COG8 – CDG	COG8	Golgi-to-ER retrograde transport	611182	606979	ID, Hy, Sz	2007	PMID: 17331980 PMID: 17220172
ATP6V0A2–CDG wrinkly skin syndrome	ATP6V0A2	Golgi pH regulator	219200 278250	611716	cutis laxa, congenital hip dislocation, joint hyperlaxity, dysmorphism, feeding problems, late closure of the fontanelles, varying CNS involvement	2008	PMID: 18157129
TMEM165–CDG	TMEM165	Golgi pH regulator and, manganese and calcium homeostasis	614727	614726	ID, Hy, M, short stature, dysmorphism, eye abnormalities, hepatomegaly, skeletal dysplasia	2012	PMID: 22683087
TMEM199–CDG	TMEM199	Golgi homeostasis	616829	616815	mild phenotype of hepatic steatosis, elevated aminotransferases, alkaline phosphatase, hypercholesterolemia, low serum ceruloplasmin	2016	PMID:26833330
CCDC115–CDG	CCDC115	Golgi homeostasis	616828	613734	storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms	2016	PMID:26833332
ATP6AP1-CDG	ATP6AP1	Golgi vacuolar ATPase	300972	300197	immunodeficiency, hepatopathy, and variable neurocognitive abnormalities	2016	PMID: 27231034
ATP6AP2-CDG	ATP6AP2	Golgi vacuolar ATPase	300423 301045 300911	300556	ID, liver disease, immunodeficiency, cutis laxa	2017	PMID: 29127204
ATP6V1A-CDG	ATP6V1A	Golgi vacuolar ATPase	617403	607027	cutis laxa, facial dysmorphism, cardiac abnormalities	2017	PMID: 28065471
ATP6V1E1-CDG	ATP6V1E1	Golgi vacuolar ATPase	617402	108746	cutis laxa, facial dysmorphism, cardiac abnormalities	2017	PMID: 28065471
VMA21-CDG	VMA21	V-ATPase assembly factor	310440	300913	Mild cholestasis, chronic elevation of transaminases, elevation of (LDL) cholesterol and steatosis	2020	PMID: 32145091
MRX108	SLC9A7	Na(+)/H(+) Exchanger	301024	300368	Nonsyndromic form of X-linked ID	2019	PMID: 30335141
Congenital myasthenic syndrome	GFPT1	glutamine-fruct-6-P transaminase 1	610542	138292	congenital myasthenic syndrome with tubular aggregates	2011	PMID: 21310273
Achondrogenesis type 1A	TRIP11	Golgi structure	200600	604505	lethal achondrogenesis, deficient ossification	2010	PMID: 20089971
PGM1–CDG Glycogen storage disease 14	PGM1	reversible conversion of Glc-1-P and Glc-6-P	614921 612934	171900	neurologically normal, split uvula, hepatopathy, hypoglycemia, rhabdomyolysis, dilated cardiomyopathy, cardiac arrest, malignant hyperthermia	2012	PMID: 22492991
HIES	PGM3	reversible conversion of GlcNAc-1-P and GlcNAc-6-P	615816	172100	severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, motor and neurocognitive impairment	2014	PMID: 24589341 PMID: 24698316
Neutropenia, severe congenital 4	G6PC3	Glc-6 phosphatase, catalytic, 3	612541	611045	severe congenital neutropenia, recurrent infections, prominent superficial veins, cardiac abnormalities	2011	PMID: 21385794
Glycogen storage disease Ib and Ic (recessive)	SLC37A4	Glc-6-P transporter	232220 232240	602671	neutrophil dysfunction	2011	PMID: 21385794
SLC37A4-CDG (dominant)	SLC37A4	Glc-6-P transporter	619525	602671	Liver dysfunction, coagulation deficiencies	2021	PMID: 33964207
NSID West syndrome	ST3GAL3	N-acetyllactosaminide α2-3 sialyltransferase	611090 615006	606494	NSID, infantile spasms, hypsarrhythmia	2011 2013	PMID: 21907012 PMID: 23252400
CDA-II	SEC23B	Golgi trafficking	224100	610512	disrupted erythropoiesis with multinucleated erythroblasts in bone marrow	2009	PMID: 19561605
Autosomal-dominant polycystic liver disease	SEC63	Golgi trafficking	174050	608648	autosomal-dominant polycystic liver disease	2004	PMID: 15133510
STX5-CDG	STX5	Golgi	N/A	603189	Multisystem disease with severe liver disease, skeletal dysplasia, facial dysmorphism, hypotonia, elevated cholesterol	2021	PMID: 34711829
GET2-CDG	CAMLG	Transmembrane Domain Recognition Complex	N/A	601118	DD, ID, Hy, epilepsy	2021	*
GET3-CDG	GET3	Transmembrane Domain Recognition Complex	N/A	601913	Progressive pediatric cardiomyopathy and early death	2019	PMID: 31461301
GET4-CDG	GET4	Transmembrane Domain Recognition Complex	N/A	612056	DD, ID, Sz, facial dysmorphism, and delayed bone age	2020	PMID: 32395830
Catel-Manzke syndrome	TGDS	TDP-Glc 4,6-dehydratase	616145	616146	Pre and postnatal growth deficiency, Pierre Robin anomaly, cardiac abnormalities, distinctive bilateral hyperphalangy of the index finger.	2014	PMID: 25480037
TRAPPC11- deficiency	TRAPPC11	Intracellular vesicle trafficking	615356	614138	Muscular dystrophy, limb-girdle or cerebral atrophy, global retardation, scoliosis, achalasia and alacrima.	2017	PMID: 23830518 PMID: 27707803
TRAPPC9-CDG	TRAPPC9	Intracellular vesicle trafficking	613192	611966	ID, microcephaly, hypoplastic corpus callosum, dysmorphic features	2022	PMID: 35042660
UGP2-CDG Developmental and epileptic encephalopathy 83	UGP2	UDP-Glc pyrophosphorylase 2 (converts Glc-1-P to UDP-Glc)	618744	191760	ID, Sz, DD, Hy, feeding difficulties, Dysmorphic facial features in some	2020	PMID: 31820119
UGDH-CDG Developmental and epileptic encephalopathy 84	UGDH	UDP-Glc dehydrogenase (converts UDP-Glc to UDP-GlcA)	618792	603370	ID, Sz, DD, Hy, feeding difficulties, Dysmorphic facial features in some	2020	PMID: 32001716
Developmental and epileptic encephalopathy-50 (DEE50) CAD-CDG	CAD	de novo pyrimidine biosynthesis	616457	114010	DD, Hy, epileptic encephalopathy	2015	PMID: 25678555
Cohen syndrome	VPS13b	Vacuolar Protein Sorting 13 Homolog B	216550	607817	ID, M, facial dysmorphism, truncal obesity, progressive retinopathy, and intermittent congenital neutropenia	2003	PMID: 24334764
GPI-anchor pathway
X-linked GPI-anchor deficiency (GPIBD4)	PIGA	GlcNAc-PI synthesis protein	300868	311770	dysmorphism, Hy, Sz, variable CNS, cardiac, urinary systems, early death	2012	PMID: 22305531
Paroxysmal nocturnal hemoglobinuria	PIGA	GlcNAc-PI synthesis protein	300818	311770	Complement-mediated hemolysis	1993	PMID: 8500164
Autosomal-recessive GPI-anchor deficiency (GPIBD16)	PIGC	GlcNAc-PI synthesis protein	617816	601730	DD/ID, Sz	2016	PMID: 27694521
Autosomal-recessive GPI-anchor deficiency (GPIBD17)	PIGH	GlcNAc-PI synthesis protein	618010	600154	Sz, moderate DD	2018	PMID:29573052 PMID:29603516
Autosomal-recessive GPI-anchor deficiency (GPIBD19)	PIGQ	GlcNAc-PI synthesis protein	618548	605754	severe DD, SZ, early death	2014	PMID: 24463883
Autosomal-recessive GPI-anchor deficiency (GPIBD14)	PIGP	GlcNAc-PI synthesis protein	617599	605938	DD, Hy, Sz	2017	PMID: 28334793
Autosomal-recessive GPI-anchor deficiency (GPIBD12)	PIGY	GlcNAc-PI synthesis protein	616809	610662	severe DD, Sz, early death	2015	PMID: 26293662
CHIME syndrome HPMRS (GPIBD5)	PIGL	GlcNAc-PI de-N-acetylase	280000	605947	ID, colobomas, heart defect, early-onset ichthyosiform dermatosis, ear anomalies (conductive hearing loss), HPMRS	2012	PMID: 22444671
West syndrome and HPMRS (GPIBD11)	PIGW	acylates the inositol ring of phosphatidylinositol in GPI-anchor biosynthesis	616025	610275	West syndrome, HPMRS	2013	PMID: 24367057
Autosomal-recessive GPI-anchor deficiency (GPIBD1)	PIGM	first α-mannosyltransferase in GPI biosynthesis	610293	610273	Sz, portal vein thrombosis, portal hypertension	2006	PMID: 16767100
HPMRS (GPIBD2)	PIGV	second α-mannosyltransferase in GPI biosynthesis	239300	610274	HPMRS 1	2010	PMID: 20802478
Autosomal-recessive GPI-anchor deficiency (GPIBD3)	PIGN	GPI ethanolamine phosphate transferase 1	614080	606097	severe neurologic impairment, Sz, lack of development, multiple congenital anomalies, early death	2011	PMID: 21493957
Autosomal-recessive GPI-anchor deficiency (GPIBD20)	PIGB	third α-mannosyltransferase in GPI biosynthesis	618580	604122	DD/ID, Hy, Sz, hyperphosphatasia	2019	PMID: 31256876
Paroxysmal nocturnal hemoglobinuria	PIGB	third α-mannosyltransferase in GPI biosynthesis	618580	604122	Complement-mediated hemolysis	2020	PMID: 33216889
Autosomal-recessive GPI-anchor deficiency (GPIBD24)	PIGF	GPI ethanolamine phosphate transferase 2/3	619356	600153	onychodystrophy, osteodystrophy, ID, SZ	2021	PMID: 33386993
HPMRS (GPIBD6)	PIGO	GPI ethanolamine phosphate transferase 3	614749	614730	HPMRS 2	2012	PMID: 22683086
Autosomal-recessive GPI-anchor deficiency (GPIBD13)	PIGG	GPI ethanolamine phosphate transferase 2	616917	616918	DD/ID, Hy, Sz	2016	PMID: 26996948
Autosomal-recessive GPI-anchor deficiency (GPIBD22)	PIGK	GPI transamidase complex	618879	605087	DD/ID, Sz, ataxia	2020	PMID: 32220290
Autosomal-recessive GPI-anchor deficiency (GPIBD18)	PIGS	GPI transamidase complex	618143	610271	DD/ID, Hy, Sz	2018	PMID: 30269814
Autosomal-recessive GPI-anchor deficiency (GPIBD7)	PIGT	GPI transamidase complex	615398	610272	ID, Hy, Sz, abnormal skeletal, endocrine, ophthalmologic abnormalities, hypophosphatasia	2013	PMID: 23636107
Paroxysmal nocturnal hemoglobinuria	PIGT	GPI transamidase complex	615399	610272	Complement-mediated hemolysis	2013	PMID: 23733340
Autosomal-recessive GPI-anchor deficiency (GPIBD21)	PIGU	GPI transamidase complex	618590	608528	DD/ID, Hy, Sz	2019	PMID: 31353022
Autosomal-recessive GPI-anchor deficiency (GPIBD15)	GPAA1	GPI transamidase complex	617810	603048	DD, Hy, Sz, cerebellar atrophy, osteopenia	2017	PMID: 29100095
Autosomal-recessive GPI-anchor deficiency (GPIBD9)	PGAP1	lipid remodeling steps of GPI-anchor maturation	615802	611655	ID with encephalopathy	2014	PMID: 24784135
HPMRS (GPIBD8)	PGAP2	lipid remodeling steps of GPI-anchor maturation	614207	615187	HPMRS 3	2013	PMID: 23561846 PMID: 23561847
HPMRS (GPIBD10)	PGAP3	lipid remodeling steps of GPI-anchor maturation	615716	611801	HPMRS 4	2014	PMID: 24439110
Early infantile epileptic encephalopathy (GPIBD23)	ARV1	associates with GlcNAc-PI synthesis enzyme, putative lipid transporter	617020	611647	ID, Hy, Sz, encephalopathy, ataxia, visual impairment	2020	PMID: 32165008
Dystroglycanopathy
Walker–Warburg syndrome (MDDGA1, B1, C1)	POMT1	O-mannosyltransferase	236670 613155 609308	607423	Walker–Warburg syndrome, brain malformations, various eye malformations, elevated serum CK	2002	PMID: 12369018
Walker–Warburg syndrome (MDDGA2, B2, C2)	POMT2	O-mannosyltransferase	613150 613156 613158	607439	Walker–Warburg syndrome, brain malformations, various eye malformations, elevated serum CK	2005	PMID: 15894594
Muscle–eye–brain disease (MDDGA3, B3, C3)	POMGNT1	O-mannosyl glycan GlcNAc-transferase	253280 613151 613157	606822	ID, severe early-onset muscle weakness, brain malformations, various eye malformations, elevated serum CK	2001	PMID: 11709191
Fukuyama-type congenital muscular dystrophy (MDDGA4, B4, C4)	FKTN	ribitol-5-phosphate transferase	253800 613152 611588	607440	Hy, ID, Sz, generalized muscle weakness, elevated serum CK	1998	PMID: 9690476
Congenital muscular dystrophy type 1C (MDDGA5, B5, C5)	FKRP	fukutin-related protein, ribitol-5-phosphate transferase	613153 606612 607155	606596	Hy, feeding difficulties, hypertrophy of lower limb muscles, wasting of shoulder girdle, variable neurological involvement, elevated serum CK	2001	PMID: 11592034
Congenital muscular dystrophy type 1D (MDDGA6, B6)	LARGE1	Xyl and GlcA transferase	613154 608840	603590	ID, white matter changes, elevated serum CK	2003	PMID: 12966029
Walker–Warburg syndrome (MDDGA7)	CRPPA	CDP-ribitol synthetase	614643	614631	brain malformations, various eye malformations, elevated serum CK	2012	PMID: 22522420 PMID: 22522421
Walker–Warburg syndrome (MDDGA8)	POMGNT2	β1-4 GlcNAc-transferase	614830	614828	brain malformations, various eye malformations	2012	PMID: 22958903
Walker–Warburg syndrome (MDDGA10)	RXYLT1	Xyl-transferase	615041	605862	brain malformations, facial clefts, retinal dysplasia, gonadal dysgenesis.	2012	PMID: 23217329
Congenital muscular dystrophy (MDDGA11)	B3GALNT2	β1-3 GalNAc-transferase 2	615181	610194	I.D, Hy, Sz, brain malformations, various eye malformations, elevated serum CK	2013	PMID: 23453667
Walker–Warburg syndrome (MDDGA12)	POMK	O-Man kinase	615249	615247	Walker–Warburg syndrome, brain and eye malformations, elevated serum CK	2013	PMID: 23929950 PMID: 23519211
Walker–Warburg syndrome (MDDGA13)	B4GAT1	β1-4 glucuronyltransferase	615287	605517	Hy, Sz, brain malformations, retinal dysplasia, elevated serum CK	2013	PMID: 23359570
Congenital muscular dystrophy (MDDGA14, B14, C14)	GMPPB	GDP-Man pyrophosphorylase B	615350 615351 615352	615320	I.D, M, brain and eye malformations, elevated serum CK	2013	PMID: 23768512
Hereditary inclusion body myopathy	GNE	UDP-GlcNAc-2-epimerase/ManAc kinase	600737 605820 269921	603824	proximal and distal muscle weakness, wasting of the upper and lower limbs, sparing of the quadriceps	2001	PMID: 11528398
Glycosaminoglycan
Ehlers–Danlos syndrome	B4GALT7	β1-4 galactosyltransferase 7	130070	604327	progeroid form with DD, short stature, osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, loose but elastic skin	1990	PMID: 2106134
Hereditary multiple exostoses	EXT1	GlcA/GlcNAc-transferase	133700	608177	multiple exostoses of the bone	1995	PMID: 7550340
Hereditary multiple exostoses (dominant)	EXT2	GlcA/GlcNAc-transferase	133700	608210	multiple exostoses of the bone	1995	PMID: 7550340
Seizures, scoliosis, and macrocephaly syndrome (recessive)	EXT2	GlcA/GlcNAc-transferase	616682	608210		2015	PMID: 26246518
Schneckenbecken dysplasia	SLC35D1	UDP-GlcA / UDP-GalNAc Golgi transporter	269250	610804	neonatal lethal chondrodysplasia, short-limbed skeletal dysplasia	2007	PMID: 17952091
SED	PAPSS2	3′-phosphoadenosine- 5′-phosphosulphate synthase	612847	603005	short-trunk stature, skeletal dysplasia, normal intelligence, variable epiphyseal and metaphyseal changes	1998	PMID: 9771708
Achondrogenesis type 1B	SLC26A2	sulfate anion transporter	222600 600972 256050	606718	early death in severe cases, adults reported: achondrogenesis Ib, usually stillborn or early death of respiratory failure; atelosteogenesis II, pulmonary hypoplasia, fatal in infants	1996	PMID: 8528239
SED, Omani type	CHST3	chondroitin 6-O-sulfotransferase	143095	603799	skeletal dysplasia, normal intelligence	2004	PMID: 15215498
Macular corneal dystrophy types I/II	CHST6	Keratan Sulphate 6-O-sulfotransferase	217800	605294	corneal clouding and erosions, painful photophobia	2000	PMID: 11017086
Osteochondrodysplasia, brachydactyly, and overlapping malformed digits	CHST11	Chondroitin 4-O-Sulfotransferase 1	618167	610128	Skeletal malformation	2015	PMID: 26436107
Ehlers–Danlos syndrome Adducted thumb-clubfoot syndrome	CHST14	dermatan sulfate GalNAc 4-O sulfotransferase 1	601776	608429	adducted thumb, clubfoot, progressive joint, skin laxity syndrome	2009 2010	PMID: 20004762 PMID: 20533528
Desbuquois dysplasia 1 Epiphyseal dysplasia, multiple, 7	CANT1	Calcium Activated Nucleotidase 1	251450 617719	613165	Severe growth delay, joint laxity, short extremities, scoliosis	2009	PMID: 19853239
Ehlers–Danlos-like syndrome or SED with joint hyperlaxity	B3GALT6	β1-3 galactosyltransferase 6	271640 615349	615291	abnormal skeletal and connective tissues lax skin, muscle hypotonia, joint dislocation, spinal deformity	2013	PMID: 23664117
Larsen-like syndrome	B3GAT3	β1-3 glucuronyltransferase 3	245600	606374	multiple joint dislocations, short stature, craniofacial dysmorphism, congenital heart defects	2011	PMID: 21763480
Desbuquois dysplasia	FAM20B	Glycosaminoglycan xylosylkinase	N/A	611063	short limb dysplasia, very short stature, joint laxity and skeletal changes	2019	PMID: 30847897
Autosomal-recessive short stature syndrome (Desbuquois dysplasia 2)	XYLT1	Xyl-transferase 1	615777	608124	moderate ID, short stature, distinct facial features, altered fat distribution	2014	PMID: 23982343
Spondyloocular syndrome with bone fragility, cataracts, and hearing defects	XYLT2	Xyl-transferase 2	605822	608125	osteoporosis, cataracts, sensorineural hearing loss, mild learning defects	2015	PMID: 26027496
Musculocontractural type of Ehlers–Danlos syndrome	DSE	dermatan sulfate epimerase	615539	605942	characteristic facial features, congenital contractures of the thumbs and feet, hypermobility of finger, elbow, and knee joints, muscle weakness	2013	PMID: 23704329
CSGALNACT1 deficiency	CSGALNACT1	chondroitin sulfate N-acetylgalactosaminyltransferase-1	618870	616615	short stature and joint laxity	2017	PMID: 27599773
EXTL3 deficiency	EXTL3	GlcA/GlcNAc-transferase	617425	605744	ID, skeletal dysplasia, Severe combined immunodeficiency	2017	PMID: 28132690 PMID: 28148688 PMID: 28331220
SLC10A7 deficiency	SLC10A7	Ca²⁺ homeostasis	618363	611459	Amelogenesis imperfecta and skeletal dysplasia with multiple dislocations	2018	PMID: 30082715 PMID: 29878199
NDST1-CDG MRT46	NDST1	N-deacetylates and N-sulfates GlcNAc in heparan sulfate	616116	600853	Nonsyndromic ID	2014	PMID: 25125150
Paganini-Miozzo syndrome (MRXSPM)	HS6ST2	Heparan Sulfate 6-O-Sulfotransferase 2	301025	300545	XLID and severe myopia	2019	PMID: 30471091
Neurofacioskeletal syndrome with or without renal agenesis	HS2ST1	Heparan Sulfate 6-O-Sulfotransferase 1	619194	604844	DD/ID, corpus callosum hypoplasia or agenesis, facial dysmorphism, skeletal abnormalities	2020	PMID: 33159882
Temtamy preaxial brachydactyly syndrome	CHSY1	β1–3 GlcA-transferase/ β1–4 GalNAc-transferase (CS elongation)	605282	608183	Bilateral, symmetric preaxial brachydactyly and hyperphalangism of digits, facial dysmorphism, dental anomalies, sensorineural hearing loss, delayed motor, growth retardation, ID	2010	PMID: 21129728
Other
Amish infantile epilepsy	ST3GAL5	Sia2,3Galβ1-4Glc-Cer synthase (GM3)	609056	604402	infantile-onset epilepsy, developmental stagnation, blindness	2004	PMID: 15502825
Salt and pepper syndrome	ST3GAL5		609056	604402	severe ID, epilepsy, scoliosis, altered dermal pigmentation, choreoathetosis, dysmorphic facial features	2014	PMID: 24026681
Complex hereditary spastic paraplegia	B4GALNT1	β1-4 GalNAc-transferase 1 (GM2)	609195	601873	early-onset spastic paraplegia, ID, cerebellar ataxia, peripheral neuropathy, cortical atrophy, white matter hyperintensity	2013	PMID: 23746551
NOR polyagglutination syndrome	A4GALT	α1–4 Gal transferase (GB3 synthase)	111400	607922	Potential for asymptomatic anemia, leukopenia, or thrombocytopenia	2012	PMID: 22965229
GALNT2-CDG	GALNT2	Polypeptide GalNAc Transferase 2	618885	602274	Global DD/ID with language deficit, autistic features, behavioral abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels	2020	PMID: 32293671
Adams–Oliver syndrome 4	EOGT	EGF-domain-specific O-linked O-GlcNAc transferase	615297	614789	aplasia cutis congenita, terminal transverse limb defects	2013	PMID: 23522784
Familial tumoral calcinosis	GALNT3	polypeptide GalNAc-transferase 3	211900	601756	massive calcium deposits in skin and tissue	2004	PMID: 15133511
Tn syndrome	C1GALT1C1	chaperone of β1-3 GalT	300622	300611	hemolytic anemia with thrombocytopenia, leukopenia	2005	PMID: 16251947
Peters plus syndrome	B3GLCT	β1-3 glucosyltransferase–specific for O-fucose on thrombospondin type 1 repeats	261540	610308	Peters eye anomaly of the anterior chamber, ID, DD, prenatal growth delay, postnatal, typically disproportionately short, cleft lip with or without cleft palate	2006	PMID: 16909395
Dowling–Degos disease 2	POFUT1	protein O-fucosyltransferase 1–specific for particular EGF repeats	615327	607491	skin disorder showing reticulate hyper- and hypopigmentation at flexure regions such as the neck, axilla, and areas below the breasts and groin	2013	PMID: 23684010
Dowling–Degos disease 4	POGLUT1	protein O-glucosyltransferase 1–specific for particular EGF repeats	615696	615618	skin disorder showing reticulate hyper- and hypopigmentation at flexure regions such as the neck, axilla, and areas below the breasts and groin	2014	PMID: 24387993
Autosomal-recessive spondylocostal dysostoses 3	LFNG	lunatic fringe–specific for O-fucose on particular EGF repeats	609813	602576	spondylocostal dysostosis with severe vertebral anomalies.	2006	PMID: 16385447
MRX106	OGT	O-GlcNAc transferase	300997	300255	X-linked intellectual disability.	2017	PMID: 28302723 PMID: 28584052
NANS deficiency	NANS	N-acetylneuraminic acid synthase	610442	605202	infantile-onset severe developmental delay and skeletal dysplasia	2016	PMID: 27213289
N-acetylneuraminate pyruvate lyase deficiency	NPL	Recycles sialic acid to ManNAc	N/A	611412	Sialuria, exercise with cardiac symptoms, intolerance/muscle wasting	2018	PMID: 30568043
GNPNAT1-CDG	GNPNAT1	Glucosamine-phosphate N-acetyltransferase (converts GlcN-6P to GlcNAc-6P)	N/A	616510	Rhizomelic skeletal dysplasia	2021	PMID: 32591345
Brain small vessel disease 3 BSVD3	COLGALT1	collagen galactosyltransferase	618360	617531	Variable onset intracranial bleeding causing DD, spasticity, porencephaly	2018	PMID:30412317
GOSR2-CDG Epilepsy, progressive myoclonic 6	GOSR2	Subunit of SNARE family of vesicle docking proteins	614018	604027	Progressive myoclonic epilepsy, ataxia	2011	PMID: 21549339
CDG Status Unknown**
Galactosemia 1	GALT	Galactose-1-phosphate uridylyltransferase	230400	606999	Failure to thrive, vomiting, cataracts, hepatomegaly, ovarian failure due to hypergonadotropic hypogonadism	2016	PMID: 26733289
Galactosemia 3	GALE	UDP-galactose-4-prime-epimerase	230350	606953	Failure to thrive, hepatomegaly, splenomegaly, Hy, ID, DD, vomiting	2021	PMID: 34159722
Fructose intolerance, hereditary	ALDOB	Aldolase B	229600	612724	Failure to thrive, hepatomegaly, Hy, ID, DD, Sz vomiting	2007	PMID: 17515832

: *, to be published soon; **, ongoing discussion with clinical and patient advocates; CDG, congenital disorders of glycosylation; CMS, congenital myasthenic syndrome; Dol, dolichol; ID, intellectual disability; Sz, seizures; Hy, hypotonia; M, microcephaly; DD, developmental delay; NSID, nonsyndromic intellectual disability; XLNSID, X-linked nonsyndromic intellectual disability; OST, oligosaccharyltransferase; CMP, cytidine monophosphate; ER, endoplasmic reticulum; CCMS, cerebrocostomandibular-like syndrome; CNS, central nervous system; HIES, hyper-IgE syndrome; CLSD, cranio-lenticulo-sutural dysplasia; CDA, congenital dyserythropoietic anemia; HPMRS, hyperphosphatasia with mental retardation syndrome; CK, creatine kinase; SED, spondyloepimetaphyseal dysplasia; EGF, epidermal growth factor; N/A, not available.

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Lefeber D, Freeze HH, Steet R, et al. Known Human Glycosylation Disorders. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology [Internet]. 4th edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2022. Online Appendix 45A.