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Line 22: |
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| ==Differential diagnosis== | | ==Differential diagnosis== |
| Leigh's disease must be differentiated from other diseases that cause neurological manifestations in infants. | | Leigh's disease must be differentiated from other diseases that cause neurological manifestations in infants. |
| {|
| | Leigh's disease must be differentiated from birth asphyxia, kernicterus, encephalitis, thiamine deficiency, Wilson's disease, biotin-responsive basal ganglia disease. Birth asphyxia and hyperbilirubinemia can cause damage to thalamus and basal ganglia, which can cause lesions similar to leigh's disease. |
| |- style="background: #4479BA; color: #FFFFFF; text-align: center;"
| |
| ! rowspan="2" |Diseases
| |
| ! colspan="4" |Type of motor abnormality
| |
| ! rowspan="2" |Clinical findings
| |
| ! 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
| |
| *[[Seizures]]
| |
| *External [[ophthalmoplegia]]
| |
| *[[Lactic acidosis]]
| |
| *[[Vomiting]]
| |
| | style="background: #F5F5F5; padding: 5px;" |
| |
| *Increased [[lactate]] levels in [[blood]] and [[CSF]]
| |
| *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]]
| |
| *[[Hepatosplenomegaly]]
| |
| *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:
| |
| **[[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
| |
| *[[Retinitis pigmentosa]]
| |
| *[[Sensorineural]] hearing loss
| |
| *[[Hepatomegaly]] and [[cirrhosis]]
| |
| *[[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
| |
| *[[Adrenal insufficiency]]
| |
| *[[Hyperpigmented]] skin
| |
| *[[Gonadal dysfunction]]
| |
| *[[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
| |
| *[[Hepatomegaly]]
| |
| *Neonatal [[seizures]]
| |
| *Profound developmental delay
| |
| *[[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]]
| |
| *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]]
| |
| *[[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]]
| |
| *[[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;" | --
| |
| |}
| |
|
| |
|
| ==Diagnosis== | | ==Diagnosis== |