Canavan disease, or spongiform leukodystrophy, is an autosomal recessive disorder caused by a deficiency of N-acetylaspartylase, which results in an accumulation of N-acetylaspartic acid in the urine, plasma, and brain. It usually manifests in early infancy as hypotonia followed by spasticity, cortical blindness, and macrocephaly . Canavan disease is a rapidly progressive illness with a mean survival time of 3 years, although protracted cases do occur. Definite diagnosis usually requires brain biopsy or autopsy.
Canavan disease is characterized at pathologic analysis by extensive vacuolization that initially involves the subcortical white matter, then spreads to the deep white matter . Electron microscopy demonstrates increased water content within the glial tissue, described as having the texture of a wet sponge, as well as dysmyelination.
图：Canavan disease in a 6-month-old boy with macrocephaly. ( a ) T2-weighted MR image shows extensive high-signal-intensity areas throughout the white matter, resulting in gyral expansion and cortical thinning. Striking demyelination of the subcortical U fibers is also noted. ( b ) T1-weighted MR image shows demyelinated white matter with low signal intensity. ( c ) Photomicrograph (original magnification, �200; hematoxylin-eosin stain) shows ballooning of the myelin sheaths of oligodendrocytes due to massive intramyelinic edema.
Krabbe's disease(球样细胞脑白质营养不良)
Krabbe disease, also known as globoid cell leukodystrophy, is one of the more common leukodystrophies, inherited in an autosomal recessive fashion. It is caused by a deficiency lysosomal enzyme galactocerebrosidase (GALC), with the genetic locus mapped to chromosome 14。 GALC deficiency results in the accumulation of galactosylsphingosine, which is considered to be neurotoxic to both the central and peripheral nervous system. The most frequent form of Krabbe disease has an infantile onset, whereas the late-onset form is rare。
Histologically, there is myelin destruction, gliosis, and the presence of the characteristic multinucleated "globoid" cells (macrophages) within the perivascular regions of the affected white matter
Krabbe's disease(或球样细胞脑白质营养不良) 是一种常染色体隐性遗传性脑白质营养不良，因缺乏半乳糖(基)脑苷脂酶溶酶体酶(GALC)引起。基因定位在14号染色体。GALC缺乏导致半乳糖基鞘氨醇积聚，后者被认为对中枢神经和周围神经都有毒性作用。Krabbe disease较多见的是婴儿时起病，迟发型少见。
组织学上：有髓鞘破坏，胶质增生，受累白质血管周围具有特征性的多聚核细胞“球样细胞”（巨噬细胞）浸润。
下图：A 16-month-old male patient
FIG 1.Axial view T2-weighted MR image (4200/90 [TR/TE]) reveals symmetric areas of T2 prolongation (arrows) within the centrum semiovale
FIG 2. Coronal view fluid-attenuated inversion recovery image (8002/137.5) reveals symmetric areas of abnormal signal intensity (arrows) within the periventricular white matter
FIG 3. Coronal view T1-weighted image (400/20) obtained after the IV administration of contrast material reveals no enhancement within the periventricular white matter (arrows)
A 33-year-old woman with talipes cavus since childhood and slowly progressive paraparesis was found to have hereditary spastic paraplegia because her brother had a similar, although milder, disorder. On neurologic examination she had talipes cavus with hammer toes, spastic paraparesis, increased deep tendon reflexes in all limbs, Babinski sign, mild wasting, and decreased vibration sense distally in the lower limbs. Nerve conduction studies showed a mild demyelinating sensory neuropathy.
下图：
A, Axial FLAIR image (9264/150/2; TI = 2200) shows increased signal intensity of the white matter of the precentral gyri, which are atrophic (arrowhead).
B, Coronal FLAIR image (9264/150/2; TI = 2200) shows the hyperintensity limited to the upper part of the motor cortex (arrows) and extending across the corpus callosum (arrowheads).
C, Midline sagittal turbo spin-echo T2-weighted image (5422/110/2) shows thin, slightly hyperintense isthmus of the corpus callosum (arrow).
The 27-year-old man first noted weakness of the right leg at age 23, with insidious progression of spasticity, more pronounced on the right side than the left. Motor-evoked response was abnormal on the left side.
下图：
A and B, Coronal T2-weighted images (3648/99/2) of adjacent sections, A posterior to B, show nearly symmetrical involvement of the corticospinal tract from the cortex (A) to the brain stem (asterisks).
C, Axial T2-weighted image (2100/90/2) at pontine level shows symmetrical pyramidal involvement (arrowhead).
Leigh病
Leigh病(LD)即亚急性坏死性脑脊髓病,是一种少见的、病因不明的常染色体隐性遗传性神经系统变性疾患,为脑脊髓灰质及白质病变,CT常示双侧对称性基底节低密度灶,主要累及婴儿及儿童。
图：Leigh disease in a 2-year-old boy. ( a ) T2-weighted MR image shows bilateral high-signal-intensity areas in the putamen and globus pallidus (arrows). ( b ) On a T1-weighted MR image, the lesions demonstrate low signal intensity (arrows).
肾上腺脑白质营养不良MRI分型
Different patterns recognized in male patients with cerebral X-linked adrenoleukodystrophy. ( a ) Pattern 1: white matter in the parieto-occipital lobe or splenium of corpus callosum; ( b ) pattern 2: white matter in the frontal lobe or genu of corpus callosum; ( c ) pattern 3: primary involvement of frontopontine or corticospinal projection fibers without affection of periventricular white matter; ( d ) pattern 4: primary involvement of cerebellar white matter; ( e ) pattern 5: combined but separate initial involvement of frontal and parieto-occipital white matter.
下图：Pattern 1
Childhood cerebral X-linked ALD in an 8-year-old boy with initial clinical findings of hearing impairment. ( a–f ) Initial T2-weighted MR images show confluent and symmetric bilateral hyperintense areas in the parieto-occipital deep white matter and in the splenium of the corpus callosum ( a, b ), increased signal intensity in the acoustic radiation ( arrows in b ), subtle changes in signal intensity in the brachium of the inferior colliculus ( arrow in c ) and lateral lemniscus ( arrow in d ), and involvement of the pyramidal tract in the pons and medulla oblongata ( arrows in e and f ). ( g ) Initial contrast material–enhanced T1-weighted MR image shows strong enhancement in the middle layer of the lesion (Schaumburg zone 2) ( white arrow ). Zones 1 ( solid black arrows) and 3 (open arrow) are not enhanced. These initial MR imaging findings suggested childhood cerebral X-linked ALD, and genetic-serologic test results confirmed the diagnosis. Although the patient underwent dietary and medical treatment, hearing impairment progressed rapidly. Visual disturbance also appeared 2 months after initial evaluation, and follow-up MR imaging was performed. ( h–k ) Follow-up MR images demonstrate more extensive bilateral signal intensity changes in the parieto-occipital white matter ( h ), interval growth of the lesions involving the brachium of the inferior colliculus ( arrows in i, solid white arrow in j ) and the lateral lemniscus ( open arrow in j, arrow in k), and signal intensity change in the right optic tract ( black arrow in j ). The latter finding was not demonstrated at initial MR imaging. ( l ) MR image obtained 6 months after initial MR imaging shows more extensive bilateral signal intensity changes in the parieto-occipital white matter, along with atrophic change in the deep white matter.
下图：Pattern 3
Childhood cerebral X-linked ALD in a clinically asymptomatic 7-year-old boy. ( a ) On an initial brain MR image, the lesion is confined to the left parietopontine tract and to isolated white matter fibers of the corticospinal tract in the posterior limb of the internal capsule. ( b ) Follow-up MR image obtained 9 months later shows slight enlargement of the lesion ( arrow ) in the left parietopontine tract.
