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| ==Differentiating {{PAGENAME}} from Other Diseases== | | ==Differentiating {{PAGENAME}} from Other Diseases== |
| ==Differential diagnosis== | | ==Differential diagnosis== |
| Metachromatic leukodystrophy must be differentiated from other diseases that cause neurological manifestations in infants.
| |
| {|
| |
| |- style="background: #4479BA; color: #FFFFFF; text-align: center;"
| |
| ! rowspan="2" |Diseases
| |
| ! colspan="4" |Type of motor abnormality
| |
| ! rowspan="2" |Clinical findings
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| ! rowspan="2" |Laboratory findings and diagnostic tests
| |
| ! rowspan="2" |Radiographic findings
| |
| |- style="background: #4479BA; color: #FFFFFF; text-align: center;"
| |
| !Spasticity
| |
| !Hypotonia
| |
| !Ataxia
| |
| !Dystonia
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Leigh syndrome]]
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Progressive [[psychomotor]] regression
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| * [[Seizures]]
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| * External [[ophthalmoplegia]]
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| * [[Lactic acidosis]]
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| * [[Vomiting]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Increased [[lactate]] levels in [[blood]] and [[CSF]]
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| * Genetic testing
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * MRI: abnormal [[white matter]] signal in the [[putamen]], [[basal ganglia]], and [[brainstem]] on T2 images
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Niemann-Pick]] disease type C
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Progressive [[neurodegeneration]]
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| * [[Hepatosplenomegaly]]
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| * Systemic involvement of [[liver]], [[spleen]], or [[lung]] preceedes [[neurologic]] symptoms
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Abnormal [[liver]] function tests
| |
| * [[Fibroblast]] cell culture with filipin staining
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * MRI:
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| **[[Cerebral]] and [[cerebellar]] [[atrophy]]
| |
| **Thinning of the [[corpus callosum]]
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |Infantile Refsum disease
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Abnormalities of the [[optic nerve]] and disc
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| * [[Retinitis pigmentosa]]
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| * [[Sensorineural]] hearing loss
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| * [[Hepatomegaly]] and [[cirrhosis]]
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| * [[Neurologic]] deterioration is slower than in [[Zellweger syndrome]] or ALD
| |
| | style="background: #F5F5F5; padding: 5px;" |Elevated plasma VLCFA levels
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Adrenoleukodystrophy]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Cognitive]] and behavioral abnormalities
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| * [[Adrenal insufficiency]]
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| * [[Hyperpigmented]] skin
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| * [[Gonadal dysfunction]]
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| * [[Neurologic]] deterioration progresses at a variable rate
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated plasma VLCFA levels
| |
| * Molecular [[genetic testing]] for mutations in the ABCD1 gene
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Zellweger syndrome]]
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Craniofacial]] dysmorphism
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| * [[Hepatomegaly]]
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| * Neonatal [[seizures]]
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| * Profound developmental delay
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| * [[MRI]] findings include [[cortical]] and [[white matter]] abnormalities
| |
| * [[Neurologic deterioration]] is rapid and infants rarely survive beyond six months of age
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated plasma VLCFA levels
| |
| * Elevated levels of [[phytanic acid]], pristanic acid, and pipecolic acid in plasma and [[fibroblasts]]
| |
| * Reduced plasmalogen in [[erythrocytes]]
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| * Molecular [[genetic]] testing for [[mutations]] in the PEX1 or PEX6 genes
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pyruvate dehydrogenase deficiency]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Lactic acidosis]]
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| * [[Seizures]]
| |
| * [[Intellectual disability]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated [[lactate]] and pyruvate levels in [[blood]] and CSF
| |
| * Abnormal PDH enzymatic activity in cultured fibroblasts
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Arginase deficiency]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Hyperammonemia]]
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| * [[Encephalopathy]]
| |
| * [[Respiratory alkalosis]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated [[ammonia]] level
| |
| * Elevated [[arginine]] level
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |Holocarboxylase synthetase deficiency
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Ketoacidosis]]
| |
| * [[Dermatitis]]
| |
| * [[Alopecia]]
| |
| * [[Seizures]]
| |
| * [[Developmental delay]]
| |
| | style="background: #F5F5F5; padding: 5px;" |Elevated levels of:
| |
| * Beta-hydroxyisovalerate
| |
| * Beta-methylcrotonylglycine
| |
| * Beta-hydroxypropionate
| |
| * Methylcitrate
| |
| * Tiglylglycine
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |Glutaric aciduria type 1
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Episodes of [[metabolic decompensation]] and [[encephalopathy]] often precipitated by [[infection]] and [[fever]]
| |
| * Rarely presents in the newborn period
| |
| * Microencephalic [[macrocephaly]]
| |
| * [[Seizures]] (approximately 20 percent)
| |
| * [[Cognitive function]] is preserved
| |
| | style="background: #F5F5F5; padding: 5px;" |Elevated levels of:
| |
| * [[glutaric acid]]
| |
| * 3-hydroxyglutaric acid
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * MRI:
| |
| **[[Frontal]] and [[temporal]] [[atrophy]]
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Ataxia telangiectasia]]
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Progressive [[cerebellar]] [[ataxia]]
| |
| * Abnormal eye movements
| |
| * [[Oculocutaneous]] [[telangiectasias]]
| |
| * Immune deficiency
| |
| * Increased risk of [[malignancy]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated serum alpha-fetoprotein level
| |
| * Low [[IgA]] and [[IgG]] levels
| |
| * [[Lymphopenia]]
| |
| * Genetic testing for [[mutation]] in the ATM gene
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pontocerebellar]] [[hypoplasias]]
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Progressive muscle [[atrophy]]
| |
| * [[Microcephaly]]
| |
| * [[Developmental delay]]
| |
| | style="background: #F5F5F5; padding: 5px;" |[[Genetic]] testing for PCH gene mutations
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * MRI :
| |
| **Small [[cerebellum]] and [[brainstem]] including the [[pons]]
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Metachromatic leukodystrophy]]
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Regression of motor skills
| |
| * [[Seizures]]
| |
| * [[Optic atrophy]]
| |
| * Reduced or absent [[deep tendon reflexes]]
| |
| * [[Intellectual disability]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Deficient arylsulfatase A enzyme activity in [[leukocytes]] or cultured skin fibroblasts
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pelizaeus-Merzbacher]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Nystagmus]]
| |
| * [[Cognitive impairment]]
| |
| * Onset in infancy
| |
| * Slowly progressive
| |
| * Language development may be normal
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Genetic]] testing for [[mutations]] in PLP1 gene
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| *MRI:
| |
| **[[White matter]] abnormalities
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Angelman syndrome]]
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Profound [[intellectual disability]]
| |
| * Postnatal [[microcephaly]]
| |
| * Typical abnormal behaviors (paroxysmal laughter, easily excitable)
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Methylation studies and [[chromosome]] microarray to detect chromosome 15 anomalies and UBE3A mutations
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Rett syndrome]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Occurs almost exclusively in females
| |
| * Normal development during first six months followed by regression and loss of milestones
| |
| * Loss of speech capability
| |
| * Stereotypic hand movements
| |
| * [[Seizures]]
| |
| * [[Autistic]] features
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Clinical diagnosis
| |
| * [[Genetic]] testing for MECP2 mutations
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Lesch-Nyhan syndrome]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Self-mutilating]] behavior
| |
| * [[Urinary]] stones due to [[hyperuricemia]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Elevated [[uric acid]] level
| |
| * Abnormal enzymatic activity of HPRT in cultured fibroblasts
| |
| * [[Genetic]] testing for HPRT gene [[mutations]]
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |Miller-Dieker lissencephaly
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * [[Lissencephaly]]
| |
| * [[Microcephaly]]
| |
| * [[Dysmorphic]] features
| |
| * [[Seizures]]
| |
| * Failure to thrive
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Cytogenetic testing for 17p13.3 microdeletion
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |-
| |
| | style="background: #DCDCDC; padding: 5px; text-align: center;" |Dopa-responsive [[dystonia]]
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | -
| |
| | style="background: #F5F5F5; padding: 5px;" | +
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Onset in early childhood
| |
| * Symptoms worsen with [[fatigue]] and exercise
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| * Positive response to a trial of [[levodopa]]
| |
| | style="background: #F5F5F5; padding: 5px; text-align: center;" |--
| |
| |}
| |
|
| |
|
| ==Epidemiology and Demographics== | | ==Epidemiology and Demographics== |