Table 4. [Inherited Disorders to Consider in the Differential Diagnosis of ML IIIα/β]. - GeneReviews®

Disorder	Gene(s)	MOI	Clinical Features of Differential Diagnosis Disorder
ML III gamma (variant ML III)	GNPTG	AR	Clinical 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	AR	Joint pain & stiffness	Absence of radiologic signs of dysostosis multiplex ⁷
Multiple epiphyseal dysplasia (MED) (See MED, AR & MED, AD.)	COL9A1 COL9A2 COL9A3 COMP MATN3 SLC26A2	AR AD

Disorder

Gene(s)

MOI

Clinical Features of Differential Diagnosis Disorder

Overlapping w/ML IIIα/β

Distinguishing from ML IIIα/β

ML III gamma (variant ML III)

GNPTG

Clinical 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

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

MPS IVB ³ (See GLB1-Related Disorders.)

GLB1

MPS VI (OMIM 253200) ⁴

ARSB

MPS VII ⁵

GUSB

Alpha-mannosidosis

MAN2B1

Slowly coarsening features
Mild dysostosis

Early hearing loss
More significant DD

Late infantile & juvenile galactosialidosis (OMIM 256540)

CTSA

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

Coarse facies
Short trunk
Short stature

Myoclonus
Seizures

Free sialic acid storage disorders (late infantile sialic acid storage disorder or Salla disease)

SLC17A5

DD
Coarse facies

Much more prominent neurodegenerative aspects
Absent/minimal dysostosis multiplex

Multiple sulfatase deficiency (mucosulfatidosis)

SUMF1

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

Joint stiffness & bone pain
Limited joint mobility

Later onset of symptoms
Absence of radiologic signs of dysostosis multiplex

Progressive pseudorheumatoid chondrodysplasia

CCN6

Joint pain & stiffness

Absence of radiologic signs of dysostosis multiplex ⁷

Multiple epiphyseal dysplasia (MED) (See MED, AR & MED, AD.)

COL9A1
COL9A2
COL9A3
COMP
MATN3
SLC26A2

AR
AD

From: GNPTAB-Related Disorders

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