Z Score,T Score, Percential Rank and Box Plot Graph
Imaging in inherited metabolic disorders
1.
2. Normal Myelination of the Brain
At birth, as seen on T1W images, myelination is present in the medulla,
dorsal midbrain, cerebellar peduncles, posterior limb of internal
capsule and ventrolateral thalamus.
Maturation proceeds from:
1. Central to peripheral
2. Inferior to superior
3. Posterior to anterior
3.
4. Presenting symptoms
Usually non-specific such as seizures,
Spasticity, ataxia, movement disorder or delay in
achieving the developmental milestones.
Biochemical tests and genetic analyses are often
negative. As a result, at least 60% of children with the
inborn errors of metabolism never receive a specific
diagnosis despite extensive investigations.
5. Classification According to Cellular Organelle
Dysfunction
The cellular organelles have distinctly different
functions in the metabolism:
mitochondria are involved mainly in
energymetabolism,
lysosomes in the degradation of
macromolecules(lipids, lipoproteins,
mucopolysaccharides) and
Peroxisomes in both anabolic and catabolic functions.
6. Classification of Metabolic Disorders on the
Basis of Organelle Disorder
Lysosomal Storage Diseases with White Matter Involvement
• Metachromatic leukodystrophy
• Krabbe disease
• Niemann-Pick disease
• Fabry disease
• GM1 gangliosidosis
• GM2 gangliosidosis
• Mucopolysaccharidosis
• Fucosidosis
• Wolman disease and cholesterol ester storage disease
• Ceroid lipofuscinosis
8. Mitochondrial Dysfunction with Leukoencephalopathy
• Leigh disease
• MELAS syndrome
• MERRF syndrome
• Kearns-Sayre syndrome
Disorders of Amino Acid and Organic Acid
Metabolism
• Canavan disease
9. White Matter Disorders with Unknown Metabolic
Defect
• Pelizaeus-Merzbacher disease (PMD)
• Alexander disease
• Congenital muscular dystrophy (Fukuyama type)
10. LYSOSOMAL STORAGE DISORDERS
Metachromatic Leukodystrophy (MLD)
most common of all the familial leukodystrophies.
autosomal recessive disorder caused by a deficiency of the
lysosomal enzyme aryl.sulfatase.
This enzyme is necessary for the normal metabolism of
sulfatides, which are important constituents of myelin
sheath.Cerebroside sulfate (galactosyl sulfatide)
abnormally accumulates within the white matter resulting
in breakdown of the membrane of the myelin sheath,
kidneys, gallbladder and other viscera.
11. Metachromatic Leukodystrophy (MLD)
The late infantile, juvenile and adult forms.
Most common type is the late infantile variety, which
usually manifests in children between 12 and 18
months of age and is characterized by motor signs of
peripheral neuropathy followed by deterioration in
intellect, speech and coordination.
The disease progresses quickly and within 2 years of
onset, gait disturbance, quadriplegia, blindness and
decerebrate posturing may be seen.
Disease progression is continuous and death occurs 6
months to 4 years after the onset of symptoms.
12. Imaging Features
The typical CT appearance of MLD is a symmetrical
lucency of the white matter, especially prominent in
the centrum semiovale and in corpus callosum.
No evidence of inflammation or contrast enhancement
and the cortical gray matter is spared.
MR features of MLD include symmetric confluent
areas of high signal within the periventricular and
cerebellar white matter on T2W images.
There is sparing of the subcortical U fibers until late in
the disease
Thus, MLD is a progressive centrifugal white matter
disease.
Metachromatic Leukodystrophy (MLD)
14. In the late onset (juvenile and adult forms) there is
predominant involvement of the frontal white matter.
In the late infantile form of MLD, the most common
type, a posterior (occipital) predominance of signal
abnormality has been reported with dorsofrontal
progression of disease.
Involvement of the corticospinal tracts may also be
seen in the late infantile form of MLD. High signal
intensity is seen on the long TR images along the path
of corticospinal tracts in the posterior limbs of the
internal capsules and brainstem
Metachromatic Leukodystrophy (MLD)
15. As the disease progresses the signal abnormality
becomes more extensive and confluent with associated
atrophy The corpus callosum (first the splenium then
the anterior portions), the internal capsule and the
deep hemispheric white matter are always involved
Metachromatic Leukodystrophy (MLD)
16.
17. In later stages, considerable atrophic dilatation of the
lateral ventricles is seen. Atrophy may be the only
finding in late adult onset cases
Metachromatic Leukodystrophy (MLD)
18. Proton MR spectroscopy frequently demonstrates
abnormality in the metabolic peaks before
conventional MR imaging.
The spectrum includes decrease NAA, abnormal
elevation of choline, myoinositol and lactate peak.
The elevation of myoinositol is highly suggestive of
MLD.
Metachromatic Leukodystrophy (MLD)
19. Lysosomal Storage Diseases with White Matter Involvement
Krabbe Disease/Globoid Cell Leukodystrophy
(GLD)
Deficiency of lysosomal enzyme beta galactocerebrosidase, an
enzyme that degrades cerebroside, a normal con
The diagnosis is made by demonstrating a deficiency of the
enzyme in peripheral blood.
Clinical Features
In the early onset form, presentation is either before or at the age
of 2 years while the late onset form presents after the age of 2
years.
In early onset GLD, CSF analysis always demonstrates an
abnormally high protein level with a normal cell count.
In the late onset form the protein level is not consistently high in
CSF.
Bone marrow transplantation has been shown to halt/reverse the
neurologic manifestation of disease.
20. Krabbe Disease/Globoid Cell Leukodystrophy (GLD)
CT findings
Hyperdense thalami, caudate nucleus and corona radiata
are characteristic but not specific for the disease.
MR findings
Most characteristic MR finding in both early and late onset
forms of GLD is high signal intensity on T2W images found
along the lengths of the corticospinal tracts.
Additional findings in the early onset form include
abnormal signal intensity within the cerebellar white
matter and deep gray nuclei (dentate, basal ganglia,
thalamus) with progressive involvement of the parieto-
occipital white matter and posterior portion of the corpus
callosuml.
21.
22. Late onset cases of GLD with primary involvement of
the parietal periventricular white matter,splenium of
the corpus callosum and corticospinal tracts may
appear similar on imaging to adrenoleukodystrophy
(ALD)
However, auditory pathway involvement is
characteristic of ALD and is not seen in GLD.
Krabbe Disease/Globoid Cell Leukodystrophy (GLD)
23. Diffusion weighted images, like MLD, may show prominent hypersignal
along the presumed progression zone of the demyelinating process
Krabbe Disease/Globoid Cell Leukodystrophy (GLD)
24. Sphingolipidosis
The sphingolipidoses involve abnormal metabolism
and accumulation of sphingolipids. Deficiency of
hexosaminidase. A alone results in GM2
gangliosidosis, the classic form of which is Tay-Sachs
disease.
Sandhoff’s disease is caused by a deficiency in both
hexosaminidase A and B. Clinical findings are
identical to that of Tay-Sachs with additional findings
of hepatosplenomegaly and bony deformities
25. Sphingolipidosis
Clinical Features
Between 3 and 6 months of age.
The initial sign is an excessive startle reflex.
A macular cherry red spot is almost always present at this
stage and psychomotor regression then begins.
Imaging Features
CT examination : Shows hyperdensities within the basal
ganglia and or thalami due to calcifications.
MR imaging :
All the white matter structures are involved except for the
corpus callosum, the anterior commissure and the
posterior limbs of the internal capsules.
26.
27. Mucopolysaccharidoses (MPS)
variable combinations of coarse facies, short stature, bony
defects, stiff joints, mental retardation, hepatosplenomegaly and
corneal clouding.
All forms of MPS are autosomal recessive except MPS type-II
(Hunter syndrome) which is X-linked recessive.
The spines in MPS are usually imaged to determine the site and
cause of cord compression which occurs frequently in MPS types
IV and VI.
The most common location for the cord compression is at the
atlantoaxial joint. Atlantoaxial subluxation may occur in these
patients as a result of laxity of the transverse ligament in
conjunction with hypoplasia of the odontoid.
28. Magnetic resonance shows a shortened odontoid with
a soft tissue mass of variable size with intermediate
signal on T1 and low signal on T2 W images. The low
signal on T2W images is a combination of unossified
fibrocartilage and reactive changes.
Another cause of cord compression at the C1 – C2 level
is dural thickening resulting from intradural
deposition of collagen and mucopolysaccharides. This
is seen as a thickening of the soft tissue proterior to the
dens with consequent cord compression.
Mucopolysaccharidoses (MPS)
29. PEROXISOMAL DISORDERS
X-linked Adrenoleukodystrophy (ALD)
X-linked ALD is caused by a deficiency of a single
enzyme, acyl CoA synthetase.
True leukodystrophy with no involvement of the gray
matter structures.
Imaging Features
CT and MR appearance
somewhat specific with symmetric areas of white
matter abnormality in the peritrigonal regions and
extending across the splenium of the corpus callosum.
31. The progression pattern is thus centrifugal and
posteroanterior
PEROXISOMAL DISORDERS
32. The central or inner zone which corresponds to
irreversible gliosis and scarring is moderately
hypointense on T1W MR imaging and markedly
hyperintense at T2W imaging.
The intermediate zone corresponding to active
inflammation is isointense or slightly hypointense and
rapidly enhances after administration of contrast.
The peripheral or outer zone representing the leading
edge of active demyelination appears moderately
hyperintense on T2W MR imaging and demonstrates
no contrast enhancement.
PEROXISOMAL DISORDERS
34. Diffusion weighted MR images
The burned out zone is hypointense, the intermediate
inflammatory zone is
Moderately hyperintense and
The most peripheral demyelinating zone is very faintly
hyperintense
PEROXISOMAL DISORDERS
37. UNCLASSIFIED LEUKODYSTROPHIES
Canavan Disease
deficient activity of the enzyme. Nacetylaspartylase,
which results in accumulation of N-acetylaspartic acid in
the urine, plasma and brain.
Only known disease with a defect in NAA metabolism.
Imaging Features
The subcortical U fibers also are usually involved.
Centripetal progression.
Typically, there is diffuse, symmetric increased signal
intensity on the T2-weighted images throughout the
white matter with relative sparing of the internal and
external capsules and corpus callosum.
41. Contrast enhancement may also be seen along the
ependymal linings of the lateral ventricles, within the
basal ganglia or even the dentate nuclei
Alexander Disease
42.
43. MITOCHONDRIAL DISORDERS/DEFECTS OF
THE RESPIRATORY CHAIN
Mitochondrial Encephalomyopathy—Lactic Acidosis and
Stroke-like Symptoms (MELAS)
Imaging Features
Basal ganglia calcifications.
bilateral symmetric or asymmetric cortical and subcortical
distribution.
The finding of multiple migrating infarct like lesions not
limited to a specific vascular territory especially in the basal
ganglia and the posterior part of the cerebral hemisphere in
children suggest MELAS syndrome
Muscle biopsy isimportant to confirm the diagnosis.
