Other neurologic manifestations

50%

Seizures, poor balance coordination, progressive cerebral atrophy in adulthood

Behavioral manifestations

50%

Hyperactivity in young children, anxiety restlessness in adolescence, apathy in adulthood; disruptive sleep patterns

Characteristic craniofacial features

90%

Macrocephaly; coarsening of facial features through childhood adolescence progressing to characteristic facial features in adults: prominent supraorbital ridges, hypertelorism, periorbital fullness, short nose w/broad nasal bridge, relatively small ears, thick vermilion of the lips, macroglossia

Recurrent infections

50%

Typically respiratory tract, ear, /or skin infections

Musculoskeletal manifestations

30%-50%

Lordosis, scoliosis, arthritis in adolescents young adults; vertebral dysplasia, rib cage abnormalities; progressive muscle wasting, joint contractures, bursitis, osteoporosis in adulthood

Skin manifestations

40%

Facial seborrhea, rosacea, angiofibromas

Gastrointestinal manifestations

40%

Chronic diarrhea or constipation, abdominal or inguinal hernias

Cytopenia(s)

40%

Typically neutropenia or thrombocytopenia Developmental delay. Individuals with aspartylglucosaminuria tend to have mild-to-moderate delays in early developmental milestones.

SGSH

MPS III (Sanfilippo syndrome)

AR

Neurodevelopmental delay challenging behaviors w/progressive mobility impairment

—

—

Clinical severity can vary.

GAGs in urine

Phenotypic presentation may be similar to AGU in those w/milder forms of MPS III.

—

—

—

GUSB

MPS VII (Sly syndrome)

AR

Intellectual decline in some; Coarse features; Dysostosis multiplex; Organomegaly

urinary chondroitin, heparan, dermatan sulfates; Beta-glucuronidase deficiency

—

IDS

MPS II (Hunter syndrome)

XL

Neurodevelopmental delay challenging behaviors w/progressive mobility impairment in males

—

—

Clinical severity can vary.

GAGs in urine

Phenotypic presentation may be similar to AGU in those w/milder forms of MPS II.; However, AGU will typically have earlier cognitive impairment compared to mild MPS II. IDUA

—

—

—

MPS I

AR

Severe form has neurodegeneration from early childhood death by adolescence.

—

—

—

Attenuated form may have normal early development w/psychomotor decline beginning in adolescence or adulthood.

GAGs in urine

The severe form has a more rapid decline in neurologic function than AGU, the attenuated form is much milder in early childhood. MAN2B1

—

—

—

Alpha-mannosidosis

AR

Coarse features; Progressive ataxia; ID; Hearing loss; Skeletal abnormalities; Recurrent infections

urinary oligosaccharides; Acid alpha-mannosidase deficiency

NGLY1

—

NGLY1-related congenital disorder of deglycosylation

AR

Mild-to-profound DD/ID; tear production; Liver dysfunction; Hyperkinetic movements (choreoathetosis, dystonia, myoclonus, tremor, dysmetria); Seizures; Sleep disorders; Neuropathy

ALT AST in early childhood that resolves spontaneously; urine mucopolysaccharides; Mild elevation of lactate; Generalized aminoaciduria

SUMF1

—

Multiple sulfatase deficiency

AR

Childhood-onset neurodegenerative disorder w/varying severity; Neonatal form is most severe, w/death by age 2 yrs.; Infantile form has a slower progression w/variable rates of psychomotor decline beginning in early childhood.

activity of at least 2 sulfatases; GAGs in urine; sulfatides in urine

T...

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