Table 4.

Inherited Disorders to Consider in the Differential Diagnosis of ML IIIα/β

DisorderGene(s)MOIClinical Features of Differential Diagnosis Disorder
Overlapping w/ML IIIα/βDistinguishing from ML IIIα/β
ML III gamma (variant ML III) GNPTG ARClinical features of ML IIIγ are similar to but milder than those of ML IIIα/β.Affected individuals are of Middle Eastern descent in most case reports.
Slowly progressive MPS I 1 IDUA AR
  • Clinical findings in ML IIIα/β overlap those observed in nearly all late-onset mild MPSs
  • Share several clinical & radiographic aspects of dysostosis multiplex
  • Evidence of more severe storage on physical exam
  • Enlarged head size in all MPSs (not seen in ML IIIα/β)
Slowly progressive MPS II 2 IDS XL
MPS IVB 3 (See GLB1-Related Disorders.) GLB1 AR
MPS VI (OMIM 253200) 4 ARSB AR
MPS VII 5 GUSB AR
Alpha-mannosidosis MAN2B1 AR
  • Slowly coarsening features
  • Mild dysostosis
  • Early hearing loss
  • More significant DD
Late infantile & juvenile galactosialidosis (OMIM 256540) CTSA AR
  • Coarse facies
  • Vertebral abnormalities
  • Infantile form can present w/nonimmune hydrops fetalis.
  • Hepatosplenomegaly
  • Myoclonus & ataxia in juvenile form
Childhood dysmorphic sialidosis (ML I) (OMIM 256550) NEU1 AR
  • Coarse facies
  • Short trunk
  • Short stature
  • Myoclonus
  • Seizures
Free sialic acid storage disorders (late infantile sialic acid storage disorder or Salla disease) SLC17A5 AR
  • DD
  • Coarse facies
  • Much more prominent neurodegenerative aspects
  • Absent/minimal dysostosis multiplex
Multiple sulfatase deficiency (mucosulfatidosis) SUMF1 AR
  • DD
  • Restricted range of motion in joints
  • Dysostosis multiplex on skeletal radiographs
  • Much more prominent neurodegenerative aspects
Osteoarthritis w/mild chondrodysplasia (OMIM 604864) 6 COL2A1 AD
  • Joint stiffness & bone pain
  • Limited joint mobility
  • Later onset of symptoms
  • Absence of radiologic signs of dysostosis multiplex
Progressive pseudorheumatoid chondrodysplasia CCN6 ARJoint pain & stiffnessAbsence of radiologic signs of dysostosis multiplex 7
Multiple epiphyseal dysplasia (MED) (See MED, AR & MED, AD.) COL9A1
COL9A2
COL9A3
COMP
MATN3
SLC26A2 		AR
AD

AD = autosomal dominant; AMPS = acid mucopolysaccharides; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance; MPS = mucopolysaccharidosis; XL = X-linked

1.

Formerly referred to as Hurler-Scheie syndrome or Scheie syndrome

2.

Also referred to as Hunter syndrome

3.

In the past, mucopolysaccharidosis type IVB was referred to as Morquio syndrome type B.

4.

Also referred to as Maroteaux-Lamy syndrome

5.

Also referred to as Sly syndrome

6.

A late-manifesting type II collagenopathy

7.

From: GNPTAB-Related Disorders

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