| | Type of motor disturbance | Clinical and radiographic features | Laboratory and diagnostic tests |
| Organic acidemias |
| Glutaric aciduria type 1 | Dystonia | - 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
- MRI findings include frontal and temporal atrophy
| - Abnormal urinary organic acid analysis (elevated glutaric acid and 3-hydroxyglutaric acid)
|
| Holocarboxylase synthetase deficiency | Hypotonia | - Ketoacidosis
- Dermatitis
- Alopecia
- Seizures
- Developmental delay
| - Abnormal urinary organic acid analysis (elevated beta-hydroxyisovalerate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate, and tiglylglycine)
|
| Urea cycle disorders |
| Arginase deficiency | Spasticity | - Hyperammonemia
- Encephalopathy
- Respiratory alkalosis
| - Elevated ammonia level
- Abnormal quantitative plasma amino acid analysis (elevated arginine level)
|
| Disorders of carbohydrate metabolism |
| Pyruvate dehydrogenase deficiency | Spasticity Ataxia Hypotonia | - Lactic acidosis
- Seizures
- Intellectual disability
| - Elevated lactate and pyruvate levels in blood and CSF
- Abnormal PDH enzymatic activity in cultured fibroblasts
|
| Peroxisomal disorders |
| Zellweger syndrome | Hypotonia | - 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
| - 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 may also be helpful
|
| Adrenoleukodystrophy and adrenomyeloneuropathy | Spasticity | Clinical features vary by specific type, and may include: - Cognitive and behavioral abnormalities
- Adrenal insufficiency
- Hyperpigmented skin
- Gonadal dysfunction
- Neurologic deterioration progresses at a variable rate
| - Elevated plasma VLCFA levels
- Molecular genetic testing for mutations in the ABCD1 gene may be helpful in cases with borderline VLCFA levels or atypical features, or in females
|
| Infantile Refsum disease | Hypotonia Ataxia | - 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
| - Elevated plasma VLCFA levels, though less pronounced than in Zellweger syndrome and ALD
|
| Lipid storage disorders |
| Niemann-Pick disease type C | Ataxia Dystonia | - Progressive neurodegeneration
- Hepatosplenomegaly
- Systemic involvement of liver, spleen, or lung precedes neurologic symptoms
- MRI shows cerebral and cerebellar atrophy and thinning of the corpus callosum
| - Abnormal liver function tests
- Fibroblast cell culture with filipin staining
|
| Mitochondrial disorders |
| Leigh syndrome | Ataxia Dystonia | - Progressive psychomotor regression
- Seizures
- External ophthalmoplegia
- Lactic acidosis
- Vomiting
- MRI shows abnormal white matter signal in the putamen, basal ganglia, and brainstem on T2 images
| - Increased lactate levels in blood and CSF
- Genetic testing for specific mutations (>20 have been described)
|
| Others |
| Angelman syndrome | Ataxia | - Profound intellectual disability
- Postnatal microcephaly
- Typical abnormal behaviors (paroxysmal laughter, easily excitable)
| - Methylation studies and chromosome microarray to detect chromosome 15 anomalies and UBE3A mutations
|
| Ataxia-telangiectasia | Ataxia | - Progressive cerebellar ataxia
- Abnormal eye movements
- Oculocutaneous telangiectasias
- Immune deficiency
- Increased risk of malignancy
| - Elevated serum alpha-fetoprotein level
- Low IgA and IgG levels
- Lymphopenia
- Genetic testing for mutation in the ATM gene
|
| Dopa-responsive dystonia | Focal dystonia Spastic diplegia | - Onset in early childhood
- Symptoms worsen with fatigue and exercise
| - Positive response to a trial of levodopa
|
| Hereditary spastic paraplegia | Spastic paraplegia | - Variable depending on specific mutation
| - >50 mutations have been identified
- Genetic testing is available for many
|
| Lesch-Nyhan syndrome | Choreoathetosis Dystonia Spasticity | - Self-mutilating behavior
- Urinary stones due to hyperuricemia
| - Elevated uric acid level
- Abnormal enzymatic activity of HPRT in cultured fibroblasts
- Genetic testing for HPRT gene mutations
|
| Metachromatic leukodystrophy | Hypotonia Ataxia | - Regression of motor skills
- Seizures
- Optic atrophy
- Reduced or absent deep tendon reflexes
- Intellectual disability
| - Deficient arylsulfatase A enzyme activity in leukocytes or cultured skin fibroblasts
|
| Miller-Dieker lissencephaly | Hypotonia or spasticity | - Lissencephaly
- Microcephaly
- Dysmorphic features
- Seizures
- Failure to thrive
| - Cytogenetic testing for 17p13.3 microdeletion
|
| Pelizaeus-Merzbacher | Spasticity Ataxia Athetosis | - Nystagmus
- Cognitive impairment
- Onset in infancy
- Slowly progressive
- Language development may be normal
- MRI shows white matter abnormalities
| - Genetic testing for mutations in PLP1 gene
|
| Pontocerebellar hypoplasias | Hypotonia Dyskinesias | Clinical features vary by specific type, and may include: - Progressive muscle atrophy
- Microcephaly
- Developmental delay
- MRI shows small cerebellum and brainstem including the pons
| - Genetic testing for PCH gene mutations (mutations in >10 genes have been described)
|
| Rett syndrome | Dystonia Spasticity | - 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 | - Clinical diagnosis
- Genetic testing for MECP2 mutations may be helpful
|
