What are some metabolic disorders?

Answer 1

Glycosylation
Purine
Total Lipodystrophy
Partial Lipodystrophy
Localized Lipodystrophy
Acquired Lipodystrophy
Acquired Partial Lipodystrophy
Barraquer-Simons Disease
Berardinelli-Seip Syndrome
Centrifugal Lipodystrophy
Cephalothoracic Lipodystrophy
Congenital Lipodystrophy
Hollaender-Simons Disease
Insulin Lipodystrophy
Koebberling-Dunnigan Syndrome
Lawrence-Seip Syndrome
Leprechaunism
Lipoatrophic Diabetes Mellitus
Membranous Lipodystrophy
Mesenteric Lipodystrophy
Nasu Lipodystrophy
Progressive Lipodystrophy
Seip Syndrome
Simons Syndrome
Smith Disease
Unilateral Partial Lipodystrophy
Whipple Disease
Carnitine Deficiency, Myopathic
Carnitine Deficiency, Primary
Carnitine Deficiency, Secondary
Muscle Carnitine Deficiency
Renal Reabsorption of Carnitine, Defect

Answer 2

Hyperthyroidism; HypOthyroidism. METABOLIC DISORDERS

This group includes a long list of diseases that affect the gray and white matter to varying degrees. This section discusses briefly the major diseases that affect primarily the white matter, including the classic leukodystrophies. The names and terminologies of these disorders are confusing because they were derived from the pathologic literature before their metabolic defects were discovered. As the specific biochemical and enzyme defects are being elucidated, these diseases are being classified more appropriately. The ones with "cause unknown" are listed under the general category of primary white matter disorders.
Ball WS, Egelhoff JC, Jones BV, Cecil KM: Metabolic, Congenital, Neurodegenerative, andToxic Disorders, in Edelman RR, Hesselink JR, Zlatkin MB, & Crues JV, eds., Clinical MagneticResonance Imaging, 3rd edition, Saunders-Elsevier, Philadelphia, 2006, Chapter 56, pp. 1656-1704.


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The classic leukodystrophies include adrenoleukodystrophy, Krabbe's globoid cell, and metachromatic leukodystrophy, and a few other less well known entities. They have in common a genetic origin and involve the peripheral nerves as well as the central nervous system. Each is caused by a specific inherited biochemical defect in the metabolism of myelin proteolipids that results in abnormal accumulation of a metabolite in brain tissue. Progressive visual failure, mental deterioration, and spastic paralysis develop early in life, however, variants of these diseases have a more delayed onset and a less progressive course. The other primary white matter disorders include Alexander's disease, Canavan disease, Cockayne's syndrome, and Pelizaeus-Merzbacher's disease.
Suzuki K, Armao D, Stone JA, Mukherji SK: Demyelinating diseases, leukodystrophies, andother myelin disorders. Neuroimag Clin North Am 11:15-36, 2001.


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All of the above white matter diseases are characterized by symmetric massive involvement of the white matter. MR imaging is very sensitive for detecting the white matter damage, but it is not very specific. Van der Knaap and his group
van der Knaap MS, Valk J, de Neeling N, et al: Pattern recognition in magnetic resonanceimaging of white matter disorders in children and young adults. Neuroradiol 33:478-493, 1991.


Close developed a computer based pattern recognition program in attempt to enhance the specificity of image interpretation. Their program uses information about brain structures involved, lesion characteristics, and special features, such as calcification, ventricular size, and enhancement with gadolinium.





Adrenoleukodystrophy

Adrenoleukodystrophy is a peroxisomal disorder that results in abnormal accumulation of very long chain fatty acids. Several forms have been described, but x-linked adrenoleukodystrophy is the classic form that presents in males between the ages of 4 and 8. The neurologic findings of visual and behavioral problems, intellectual impairment and long tract signs can appear before or after adrenal gland insufficiency. Adrenoleukodystrophy is both a demyelinating and dysmyelinating disorder. Initially, it involves predominantly the parietal-occipital lobes and posterior visual pathways, but it extends forward into the frontal and temporal lobes as the disease progresses. Unlike the focal plaque-like character of multiple sclerosis, adrenoleukodystrophy tends to be contiguous within fiber tracts and often is confluent within the larger white matter bundles of the centrum semiovale.
Moser HW, Loes DJ, Melham ER, et al: X-linked adrenoleukodystrophy: overview and prognosisas a function of age and brain magnetic resonance imaging abnormality. A study involving 372patients. Neuropediatrics 31(5):227, 2000.


Close Both periventricular and subcortical white matter are affected, and in advanced disease the internal capsule, corpus callosum, corticospinal tracts and other white matter fiber tracts in the brain stem can be involved.

The typical MR findings are large, symmetric, hyperintense lesions on T2-weighted images that are also clearly visible as hypointense areas on T1-weighted scans. The white matter abnormalities tend to be confluent and of homogeneous signal intensity. Sites of active demyelination along the advancing edges may be associated with blood-brain barrier disruption and enhance with paramagnetic contrast agents. Atypical features include frontal lobe involvement, unilateral involvement, calcifications and mass effect.
Demaerel P, Faubert C, Wilms G, et al: MR findings in leukodystrophy. Neuroradiol 33:368-371, 1991.


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Krabbe's Disease (Globoid Cell Leukodystrophy)

This autosomal recessive disorder presents shortly after birth and progresses rapidly. A deficiency of the enzyme galactocerebroside beta-galactosidase is the lysosomal defect that results in profound loss of myelin and destruction of oligodendrocytes. Production and maintenance of myelin is deficient; the little myelin that is formed is normal morphologically and biochemically. Characteristic globoid cells with crystalloid cytoplasmic inclusions and extensive reactive gliosis accompany the deficient myelination histologically. Macrocephaly and marked ventricular dilatation are other features of Krabbe's disease. MR images reveal bilateral, confluent involvement of the cerebral and cerebellar white matter. The margins of the lesions may enhance.
Demaerel P, Wilms G, Verdru P, et al: MR findings in globoid cell leukodystrophy. Neuroradiol32:520-522, 1990.


Close , Zarifi MK, Tzika AA, Astrakas LG, et al: Magnetic resonance spectroscopy and magneticresonance imaging findings in Krabbe's disease. J Child Neurol 16(9):657, 2001.


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Early increased attenuation on CT scans has been noted in the cerebellum, brain stem, thalamus, caudate, and corona radiata. These areas disclose corresponding hypointensity on T2-weighted scans and normal to hyperintensity on T1-weighted scans, suggesting a some paramagnetic effect, probably from calcium deposition in those brain structures.
Baram TZ, Goldman AM, Percy AK: Krabbe disease: specific MRI and CT findings. Neurology36:111-115, 1986.


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Metachromatic Leukodystrophy

This is a lysosomal disorder with autosomal recessive inheritance. A deficiency of arylsulfatase A results in accumulation of sulfatides in the brain and other organ systems. It is primarily a dysmyelinating disorder, shows no predilection for the parietal-occipital white matter, and initially spares the arcuate fibers. The cerebellar white matter is commonly affected. Overall, the distribution is symmetrical, and the lesions of metachromatic leukodystrophy do not enhance. Some patients exhibit T2 shortening in the thalamus, posterior limb of internal capsule, cerebellum, and quadrigeminal plate, which has been attributed to a paramagnetic effect from elevated levels of micro-dispersed iron due to dopamine depletion.
Sener RN: Metachromatic leukodystrophy: diffusion MR imaging findings. AJNR 23(8):1424,2002.


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Alexander's Disease

No biochemical marker has been identified in Alexander's disease, so the diagnosis must be established by clinical criteria and brain biopsy. Astrocytic eosinophilic Rosenthal fibers are the characteristic histologic findings. It presents early in infancy with psychomotor retardation, and a progressive downhill course ensues with seizures and spasticity.
van der Knaap MS, Naidu S, et al: Alexander Disease: Diagnosis with MR Imaging. AJNR22:541-552, 2001.


Close It has two distinctive imaging features, namely macrocephaly and a predilection for the frontal white matter. Contrast enhancement can be seen during the acute phases of dysmyelination and demyelination. In late stage disease more global involvement of the white matter is the rule, and brain atrophy also develops. Schuster V, Horwitz AE, Kreth HW: Alexander's disease: cranial MRI and ultrasound findings. Pediatr Radiol 21:133-134, 1991.


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Canavan’s Disease (Spongiform Leukodystrophy)

Canavan disease is an autosomal recessive disorder, and an enzymatic defect in N-acetylaspartylase has been identified. Vacuoles distributed throughout the white matter gives it a spongy appearance on histologic examination. Macrocephaly may be the first clinical clue, the MR scan may show dramatic bilateral white matter abnormality before 1 year of age and before the neurological deficits become apparent. Rapidly progressive demyelination leads to severe motor and mental retardation, blindness, and a fatal outcome by 3 years of age. The MR appearance is nonspecific and similar to the other hereditary disorders.
Brismar J, Brismar G, Gascon G, et al: Canavan disease: CT and MR imaging of the brain. AJNR 11:805-810, 1990.


Close Proton spectroscopy shows markedly elevated NAA (N-acetyl aspartate), which is quite specific for Canavan’s disease.





Pelizaeus-Merzbacher Disease

No biochemical marker has been discovered in this x-linked recessive disorder. The dominant feature is profound hypomyelination of the cerebral hemispheres and brain stem secondary to deficient production of myelin proteins. The presence of no or very little myelin suggests an arrest of myelination before or shortly after birth. Spared areas of normal myelin in the perivascular regions produces a characteristic tigroid appearance pathologically that is reflected on MR images as scattered foci of T2 hyperintensity.
van der Knaap MS, Valk J: The reflection of histology in MR imaging of Pelizaeus-Merzbacherdisease. AJNR 10:99-103, 1989.


Close Bilateral symmetric involvement of the white matter and brain atrophy are nonspecific findings. Hypointensity in basal ganglia and thalamus on T2-weighted scans suggests pathologic iron storage. Pizzini F, Fatemi A.S, et al: Proton MR spectroscopic imaging in Pelizaeus-Merzbacher disease.AJNR 24(8):1683-9, 2003.


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Cockayne's Syndrome

The hallmark of this disorder is diffuse hypomyelination similar to Pelizaeus-Merzbacher disease. Sparing of the perivascular myelin is also a feature of this disease. The specific metabolic defect has not been determined, but the genetic transmission appears to be autosomal recessive. MR images demonstrate patchy, confluent T2 hyperintensity in the white matter of the cerebral and cerebellar hemispheres without lobar preference. One distinguishing feature is calcification of the basal ganglia, dentate nucleus, and periventricular white matter.
Boltshause E, Yalcinkaya C, Wichmann W, et al: MRI in Cockayne syndrome type I. Neuroradiology 31:276-277, 1989.


Close , Damaerel P, Wilms G, Verdru P, et al: MRI in the diagnosis of Cockayne's syndrome: one case. J Neuroradiol 17:157, 1990.


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Two metabolic disorders, Hurler's disease and Lowe's syndrome, are associated with cystic changes in the cerebral white matter. Hurler's disease is one of the mucopolysaccharidoses, caused by an enzymatic defect in the degradation of heparan, dermatan, or keratan sulfate. The cystic lacunar lesions in the white matter are dilated perineuronal spaces filled with mucopolysaccharide gargoyle cells.
Murata R, Nakajima S, Tanaka A, et al: MR imaging of the brain in patients withmucopolysaccharidosis. AJNR 10:1165-1170, 1989.


Close Lowe's syndrome, one of the aminoacidurias also known as the oculocerebral renal syndrome, results from defects in the amino acid transport mechanism. In addition to the renal deficiencies, these patients develop ocular problems and patchy white matter lesions with cystic components. O'Tuama L, Laster DW: Oculocerebrorenal syndrome: Case report with CT and MR correlates. AJNR 8:555-557, 1987.


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Leigh’s Disease

Leigh's Disease (subacute necrotizing encephalomyelopathy) is a familial disorder with autosomal recessive inheritance. Onset is usually in the first year of life in more than half of cases but occasionally it can present in adulthood. Presenting signs and symptoms range from hypotonia, seizures and myoclonic jerks in the first year of life to ataxia, dysarthria and nystagmus in the second year. Death, most often from respiratory failure, usually occurs before 3 years of age. The exact biochemical defect remains unknown but may involve pyruvate metabolism. Bilaterally symmetric foci of necrosis and spongiform degeneration are noted pathologically. CT has revealed symmetric areas of decreased attenuation in the basal ganglia, brain stem and cerebellum. MR has shown these same lesions as areas of increased T2-signal and has also shown involvement of the tectum, tegmentum and medullary olive in instances when CT has been negative in these areas.
Medina L, Chi TL, DeVivo DC, et al. MR findings in patients with subacute necrotizingencephalomyelopathy (Leigh syndrome): correlation with biochemical defect. AJNR 1990;11:379.


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Leigh’s disease and other mitochondrial encephalopathies, such as MERRF (mitochondrial encephalopathy with red ragged fibers) and MELAS (mitochondrial encephalopathy with lactic acidosis and strokes) show increased brain lactic on proton MR spectroscopy.
Abe K, Yoshimura H, Tanaka H, et al: Comparison of conventional and diffusion-weighted MRIand proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis,and stroke-like events. Neuroradiology. 2003.


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Wilson’s Disease

Wilson’s disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism. Onset of symptoms is usually during the second or third decades. The classic syndrome is dysphagia, slowness and rigidity of movements, dysarthria and tremor. Pathologic changes primarily involve the lentiform nuclei and range from frank cavitation to softening and atrophy. MR has demonstrated abnormally increased T2-signal in the putamen and caudate most commonly but also in the thalamus, dentate nuclei, midbrain and subcortical white matter.
Prayer L, Wimberger D, Kramer J, e al. Cranial MRI in Wilson's disease. Neuroradiol 1990;32:211.


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Hallervorden-Spatz Disease

Hallervorden-Spatz disease is a progressive movement disorder in which there is abnormal iron deposition in the globus pallidus, reticular zone of the substantia nigra and red nucleus. It is inherited as an autosomal recessive trait. Onset is in late childhood or early adolescence with both corticospinal and pyramidal motor findings. MR has revealed decreased T2-signal in the lentiform nuclei and perilentiform white matter, related to this excess iron deposition. Areas of increased signal in the periventricular white matter have been noted and these may correlate with disordered myelination. Disproportionate atrophy of the brainstem and cerebellum is also seen.
Gallucci M, Cardonaf, Arachi M, et al. Follow-up MR studies in Hallervorden-Spatz disease.JCAT 1990; 14:118.