Sialidosis (256550*)

Neuraminidase 1 (sialidase)

Type I (cherry-red macular spot-myoclonus syndrome, mild form)

Onset: 8–25 years

Urine metabolites: Increased sialyloligosaccharides

Clinical features: Cherry-red macular spot, insidious vision loss, cataracts, progressive myoclonus and ataxia, normal intelligence, increased deep tendon reflex

Treatment: Supportive care

Type II (congenital, infantile, juvenile, and childhood forms)

Onset: In congenital form, in utero

In infantile form, birth to 12 months

In juvenile and childhood forms, 2–20 years

Urine metabolites: Increased sialyloligosaccharides

Clinical features: All of features of type I plus coarse facies, hypotonia, hepatomegaly, ascites, inguinal hernia, growth delay, muscle wasting, laryngomalacia, dysostosis multiplex

Treatment: Supportive care

Galactosialidosis (Goldberg syndrome, combined neuraminidase and beta-galactosidase deficiency; 256540*)

1. Neonatal form

2. Late infantile form

3. Juvenile/adult form

Protective protein/cathepsin A (PPCA)

Onset: In neonatal form, birth to 3 months

In late infantile form, 1st year

In juvenile/adult form, adolescence but with wide variability

Urine metabolites: Elevated sialyloligosaccharides but no free sialic acid

Clinical features: Coarse facies, corneal clouding, cherry-red macular spot, intellectual disability, seizures, dysostosis multiplex, hearing loss, hemangiomas, valvular heart disease

Treatment: Supportive care

Sialolipidosis (phospholipidosis; mucolipidosis IV, Berman disease; 252650*)

Onset: 1st year

Urine metabolites: No mucopolysaccharides

Clinical features: Severe (Berman disease) and mild forms

Developmental delay, corneal opacities, visual deficiency, strabismus, hypotonia, increased deep tendon reflexes; no radiographic skeletal abnormality, macrocephaly, or organomegaly

Treatment: Supportive care

Mannosidosis

Onset: In type I, 3–12 months

In type II, 1–4 years

Urine metabolites: Mannose-rich oligosaccharides

Clinical features: Coarse facies, macrocephaly, macroglossia, cataracts, gingival hypertrophy, slight hepatosplenomegaly, dysostosis multiplex, hypotonia, hearing loss, bowed femur, pancytopenia, recurrent respiratory infections, immunodeficiency and autoimmunity, developmental disabilities

Treatment: Supportive care, consideration of bone marrow or stem cell transplantation

Alpha-mannosidosis (248500*), type I (severe) or II (mild)

Alpha-D-mannosidase

Beta-mannosidosis (248510*)

Beta-D-mannosidase

Onset: 1–6 years

Urine metabolites: Disaccharides, mannosyl-(1-4)-N-acetylglucosamine, heparan sulfate

Clinical features: Coarse facies, deafness, delayed speech, hyperactivity, genital angiokeratoma, tortuous conjunctival vessels

Treatment: Supportive care, consideration of bone marrow or stem cell transplantation

Fucosidosis (230000*)

1. Type I (severe infantile form)

2. Type II (mild form)

Alpha-L-fucosidase

Onset: In type I, 3–18 months

In type II, 1–2 years

Urine metabolites: Oligosaccharides

Clinical features: Short stature, growth delay, coarse facies, macroglossia, cardiomegaly, recurrent respiratory infections, dysostosis multiplex, hernias, hepatosplenomegaly, angiokeratoma, anhidrosis and elevated sweat chloride, developmental disability, hypotonia changing to hypertonia, cerebral atrophy, seizures, spastic quadriplegia, vacuolated lymphocytes

Most patients from Italy or southwestern US

Treatment: Supportive care, consideration of bone marrow or stem cell transplantation

Aspartylglucosaminuria (208400*)

N-Aspartylglucosaminidase

Onset: 2–6 years

Urine metabolites: Aspartylglucosamine

Clinical features: Growth delay, microcephaly, cataracts, coarse facies, macroglossia, mitral insufficiency, hepatomegaly, diarrhea, hernias, recurrent respiratory infections, macro-orchidism, mild dysostosis multiplex, angiokeratoma corporis diffusum, acne, developmental disabilities, hypotonia, spasticity, cerebral atrophy, seizures, speech delay, hoarse voice

Increased frequency in Finnish populations

Treatment: Supportive care, consideration of bone marrow or stem cell transplantation

Winchester syndrome (277950*)

Metalloproteinase-2

Onset: Early infancy

Urine metabolites: None

Clinical features: Short stature, coarse facies, corneal opacities, gingival hyperplasia, joint contractures, osteoporosis, kyphoscoliosis, vertebral compression, carpotarsal osteolysis, ankylosis of small joints of feet, diffuse thickened skin, hyperpigmentation, hypertrichosis

Treatment: Supportive care

Schindler disease

N-Acetyl-galactosaminidase

Type I (infantile severe form; 609241*)

Onset: 8–15 months

Urine metabolites: Oligosaccharides and O-linked sialopeptides

Clinical features: Cortical blindness, optic atrophy, nystagmus, strabismus, osteopenia, joint contracture, muscular atrophy, developmental delay and regression, myoclonus, seizures, spasticity, hyperreflexia, decorticate posturing, neuraxonal dystrophy

Treatment: Supportive care

Type II (Kanzaki disease, adult-onset form; 609242*)

Onset: Adulthood

Urine metabolites: Oligosaccharides and O-linked sialopeptides

Clinical features: Coarse facies, deafness, conjunctival and retinal vascular tortuosity, angiokeratoma corporis diffusum, telangiectasia, lymphedema, mild intellectual impairment, peripheral axonal neuropathy

Treatment: Supportive care

Type III (intermediate form; 609241*)

Onset: Childhood

Urine metabolites: Oligosaccharides and O-linked sialopeptides

Clinical features: Intermediate between types I and II; variable and ranging from seizures and moderate psychomotor retardation to mild autistic features with speech and language delay

Treatment: Supportive care

Congenital disorders of N-glycosylation (CDG), type I (pre-Golgi glycosylation defects)

Onset: Mostly infancy or childhood

Clinical features (some or most of the following): Growth failure, prominent forehead with large ears, high-arched or cleft palate, strabismus, retinitis pigmentosa, pericardial effusion, cardiomyopathy, hepatomegaly, vomiting, diarrhea, liver fibrosis, primary ovarian failure, renal cysts, nephrosis, proximal tubulopathy, kyphosis, joint contractures, ectopic fat pads, orange-peel skin, muscle weakness, hypotonia, strokelike episodes, seizures, olivopontine hypoplasia, peripheral neuropathy, hypothyroidism, hyperinsulinism, factor XI deficiency, antithrombin III deficiency, thrombocytosis, decreased IgA and IgG, leukocyte adhesion defect (in type IIc), hypoalbuminemia, hypocholesterolemia, increased disialotransferrin and asialotransferrin bands when isoelectric focusing of serum transferrin is done

Treatment: Supportive care

CDG Ia (solely neurologic and neurologic-multivisceral forms; 212065*)

Phosphomannomutase-2

CDG Ib (602579*)

Mannose (Man) phosphate (P) isomerase

CDG Ic (603147*)

Dolichyl-P-Glc:Man(9)GlcNAc(2)-PP-dolichol glucosyltransferase

CDG Id (601110*)

Dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichol mannosyltransferase

CDG Ie (608799*)

Dolichyl-P-mannose synthase

CDG If (609180*)

Protein involved in mannose-P-dolichol utilization

CDG Ig (607143*)

Dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase

CDG Ih (608104*)

Dolichyl-P-glucose:Glc-1-Man-9-GlcNAc-2-PP-dolichyl-alpha-3-glucosyltransferase

CDG Ii (607906*)

Alpha-1,3-mannosyltransferase

CDG Ij (608093*)

UDP-GlcNAc:dolichyl-phosphate N-acetylglucosamine phosphotransferase

CDG Ik (608540*)

Beta-1,4-mannosyltransferase

CDG Il (608776*)

Alpha-1,2-mannosyltransferase

Congenital disorders of N-glycosylation, type II (Golgi defects)

Same as for type I, except isoelectric focusing of serum transferrin shows increased monosialotransferrin, disialotransferrin, trisialotransferrin, and asialotransferrin bands

For type IIb, normal pattern

CDG IIa (212066*)

Mannosyl-alpha-1,6-glycoprotein-beta-1,2-N-acetylglucosminyltransferase

CDG IIb (606056*)

Glucosidase I

CDG IIc (Rambam-Hasharon syndrome; 266265*)

GDP-fucose transporter-1

CDG IId (607091*)

Beta-1,4-galactosyltransferase

CDG IIe (608779*)

Oligomeric Golgi complex-7