Autosomal recessive metabolic disease

Synopsis

 systemic anomalies

• birth length less than normal
• deceleration of linear growth during first year
• birth weight less than normal
• progressive failure to thrive
• Hurler-like body configuration
• marked growth retardation
• death in childhood
• death often secondary to pneumonia or congestive heart failure

 high, narrow forehead
 long philtrum
 coarse facial features
 recurrent episodes of otitis media
 thick, firm earlobes
 thin eyebrows
 puffy eyelids
 epicanthal folds
 clear to faintly hazy corneas
 increased corneal diameter
 corneal opacities on slit-lamp exam
 low nasal bridge
 anteverted nostrils
 progressive alveolar ridge hypertropy
 macroglossia
 congestive heart failure
 hypertrophic cardiomyopathy
 cardiomegaly
 cardiac murmur
 aortic insufficiency
 recurrent bronchitis
 recurrent pneumonia
 widely spaced nipples
 scapular hypoplasia
 broad, spatulate-appearing ribs
 diastasis recti
 abdominal protuberance
 umbilical hernia
 hepatomegaly
 minimal splenomegaly
 inguinal hernia
 moderate joint limitation
 osteopenia in early infancy
 pathologic fractures
 thickened cranium
 normal enlarged sella turcica
 dorsolumbar kyphosis
 atlantoaxial dislocation
 ovoid vertebral bodies
 narrowness of interpediculate distances in lower thoracic
 hypoplastic odontoid process
 beaking of vertebral bodies T12-L3
 lumbar gibbus
 flared iliac wings
 horizontal acetabular roofs
 supra-acetabular constriction
 hip dislocation
 irregular contours of pubis and ischium
 cortical bone erosion (especially proximal femora)
 long bone shortening
 widened metaphyses
 varus deformity of humeral neck
 tilted distal ends of radius and ulna
 broadening of wrist
 brachyphalangia
 hypoplasia of carpal bones
 conical bullet-shaped distal ends of phalanges
 claw-hand deformities
 talipes equinovarus
 thick, relatively tight skin
 cavernous hemangioma
 devere psychomotor retardation
 developmental delay
 myelopathy
 neonatal hypotonia
 hoarse voice
 inclusion bodies (membrane-bound vacuoles) in fibroblasts

LABORATORY ABNORMALITIES

 Normal to mildly increased mucopolysacchariduria
 Increased serum beta-hexosaminidase (10-20x)
 Increased serum iduronate sulfatase (10-20x)
 Increased serum arylsulfatase A (10-20x)
 Deficiency of N-acetylglucosamine-1-phosphotransferase

Etiology

 mucolipidosis II is caused by mutation in the GNPTAB gene (MIM.607840)