Table 4.

Genes of Interest in the Differential Diagnosis of Mucopolysaccharidosis Type III

GeneDiffDx
Disorder
MOIClinical Features of DiffDx Disorder
Overlapping w/MPS IIIDistinguishing from MPS III
GNPTAB ML II AR
  • Coarse facies
  • Frequent ear infections
  • Inguinal & umbilical hernias
  • Dysostosis multiplex
  • Corneal clouding
  • Significant DD seen in 1st year of life
  • Death at age ~2 yrs from neurologic decline & multisystem involvement
ML III alpha/beta
  • Coarse facies
  • Frequent upper-respiratory & ear infections
  • Dysostosis multiplex
  • Slight corneal clouding
  • Normal to mildly impaired cognitive development
IDUA MPS I AR
  • Coarse facies
  • Frequent upper-respiratory & ear infections
  • Inguinal & umbilical hernias
  • DD & cognitive decline in severe form of disease
  • Hepatosplenomegaly
  • Dysostosis multiplex
  • Placid behavior in contrast to aggressive or hyperactive
  • Abnormal heparan & dermatan sulfate in urine GAG analysis
  • Corneal clouding
  • Hydrocephalus
IDS MPS II XL
  • Coarse facies
  • Frequent upper-respiratory & ear infections
  • Inguinal & umbilical hernias
  • DD & cognitive decline in severe form of disease
  • Behavioral abnormalities
  • Hepatosplenomegaly
  • Dysostosis multiplex
  • Observed almost exclusively in males
  • Abnormal heparan & dermatan sulfate in urine GAG analysis
  • Hydrocephalus
SUMF1 Multiple sulfatase deficiency AR
  • Hepatosplenomegaly
  • DD & cognitive impairment
  • Psychomotor regression
  • Hirsutism
  • Coarse facies
  • Ichthyosis
  • Abnormal enzymatic activity for multiple sulfatases
RAI1 Smith-Magenis syndrome See footnote 1
  • Speech delay
  • DD & cognitive impairment
  • Sleep disturbance
  • Behavioral outbursts
  • Hyperactivity
  • Infantile hypotonia & failure to thrive
  • Mild-to-moderate ID w/out regression
  • Characteristic dysmorphic facies
  • Stereotypic "lick & flip" & "self-hug" behaviors

AR = autosomal recessive; DD = developmental delay; DiffDx = differential diagnosis; ID = intellectual disability; ML = mucolipidosis; MOI = mode of inheritance; MPS = mucopolysaccharidosis; XL = X-linked

1.

Smith-Magenis syndrome is caused either by a 17p11.2 deletion that includes RAI1 or, less commonly, by a pathogenic variant in RAI1. Virtually all occurrences are de novo.

From: Mucopolysaccharidosis Type III

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