what-when-how
In Depth Tutorials and Information
include central nervous system disease, myopathy, con-
nective tissue disease, skeletal anomalies and intrauter-
ine restriction.
8
Decreased muscle mass and limitation
of movement may result in fractures due to both osteo-
porosis (from disuse) and mechanical factors (tight ten-
dons attached to the relatively soft bones of an infant or
young child).
Preterm infants, particularly those who have had bowel
resection for necrotizing enterocolitis, are susceptible to
nutritional deficiency, and in its most severe form it can
mimic type III OI. Severe nutritional deficiencies due
to prematurity can be differentiated from OI by docu-
mentation of deficiencies on laboratory analysis and
/
or excluding OI by DNA testing or analysis of collagen
biosynthesis. In late infancy, vitamin D deficiency (most
often due to breast feeding without adequate vitamin
D supplementation) and other nutritional deficiencies
typically present with rachitic changes on radiographs,
which distinguish these disorders from OI.
Bruck Syndrome
Bruck syndrome is an autosomal recessive disorder
characterized by fractures, short stature and progressive
scoliosis, and is distinguished from OI by the presence
of congenital contractures with pterygia. Bruck syn-
drome is genetically heterogeneous (i.e., caused by more
than one gene) and may be divided into Bruck syn-
drome-1 and Bruck syndrome-2, although there are no
evident phenotypic differences between the two groups.
Bruck syndrome-1 is caused by mutations in
FKBP10
,
which can also cause severe, recessive forms of OI.
9
Bruck syndrome-2 is caused by mutations in
PLOD2
.
10
Childhood
/
Adolescence
Mucolipidosis Type II (I-Cell Disease)
This rare autosomal recessive lysosomal enzyme dis-
order is due to a deficiency in the metabolism of one or
more types of mucopolysaccharides or glycosamino-
glycans. It is associated with mutations involving the
GNPTAB
gene. Mucolipidosis (ML) type II may pres-
ent with a rickets-like picture and fractures.
15
In addi-
tion to a rickets-like clinical presentation, transient
neonatal hyperparathyroidism has been observed in
infants with ML type II.
16
The osteodystrophy of this
disorder as described by David-Vizcarra et al. includes
normal serum calcium and phosphate and normal alka-
line phosphatase. However, serum osteocalcin and urine
deoxypyridinoline
/
creatinine were elevated suggest-
ing high bone turnover. Patients may also present with
dwarfism, kyphoscoliosis and cardiomegaly associated
with extensive pulmonary fibrosis.17
17
Geroderma Osteodysplasticum
Geroderma osteodysplasticum (previously termed
Walt Disney dwarfism) is a rare autosomal recessive dis-
order that presents with short stature, osteoporosis and
fractures, and is distinguished from OI by the presence
of loose, wrinkly skin. Geroderma osteodysplasticum is
caused by mutations in
GORAB
.
11
Osteoporosis Pseudoglioma (OPPG) Syndrome
OPPG is an autosomal recessive disorder characterized
by short stature and fractures, which result in progressive
deformity, and is distinguished from OI by the presence
of leukocoria (which is a white, rather than red, pupillary
reflex). The term pseudoglioma is confusing; it is intended
to indicate the presence of leukocoria, which is also seen
in retinoblastoma (and hence the term “
pseudo
glioma”).
In OPPG, there is
no
retinoblastoma, glioma or other
tumor. The leukocoria in OPPG is secondary to develop-
mental abnormalities of the retina and retinal vasculature
and can result in vitreous hemorrhage, retinal detach-
ment and blindness.
12
OPPG is caused by mutations in
LRP5
.
13
Carriers or those heterozygous for a mutation and
normal allele at
LRP5
have been found to have low bone
mineral density.
14
Additionally, both dominant and reces-
sive forms of familial exudative vitreoretinopathy (FEVR)
are caused by mutations in
LRP5
.
14
Therefore one could
consider LRP5 disorders as a spectrum, with OPPG being
the most severe end of the spectrum and FEVR being the
mildest end.
Idiopathic Juvenile Osteoporosis
Juvenile idiopathic osteoporosis is a non-hereditary,
transient form of childhood osteoporosis. It presents in
previously healthy children with metaphyseal long bone
fractures and vertebral compression fractures. Biopsies
have demonstrated decreased bone trabeculae and tra-
becular thinning due to defective remodeling of cancel-
lous bone with normal cortical bone remodeling.
18
In
virtually all individuals with juvenile idiopathic osteopo-
rosis, there is normalization of bone density by the end of
puberty, although spine deformity and functional limita-
tions may persist. Juvenile idiopathic osteoporosis is dis-
tinguished from OI type I by normal DNA testing of type
I collagen genes.
Exercise-Related Osteoporosis
The question of an OI diagnosis arises when children
or adolescents in heavy exercise programs such as high
school athletics, ballet or rowing experience fractures,
particularly one or more stress fractures. Frequently
females may have secondary amenorrhea and low body
Vitamin and Mineral Deficiencies
Insufficient nutritional intake, impaired intestinal
absorption and inappropriate renal loss of vitamins
and minerals can result in low bone mass and fractures.
