Table 2.

Disorders with Dystonia and MRI Signal Abnormality in the Basal Ganglia to Consider in the Differential Diagnosis of MECR-Related Neurologic Disorder

Differential DisorderGene(s)MOIClinical Features of Differential Disorder
Overlapping w/MECR-related neurologic disorder 1Distinguishing from MECR-related neurologic disorder
Leigh syndrome
(See Nuclear Gene-Encoded Leigh Syndrome Overview & Mitochondrial DNA-Associated Leigh Syndrome and NARP.)		See footnote 2.AR, XL, Mit
  • Optic atrophy may develop.
  • Symptoms may worsen following febrile illness.
Typically seen:
  • Seizures, encephalopathy, cognitive regression
  • ↑ blood/CNS lactate
May be seen on MRI:
  • Signal abnormality in brain stem in addition to basal ganglia lesions
Leber hereditary optic neuropathy See footnote 3.MitOptic atrophy is the main manifestation.Onset usually after 3rd decade (although childhood onset has been reported)
Glutaric aciduria type 1
(OMIM 231670)		 GCDH AR
  • Cognition may be preserved.
  • Symptoms may worsen following febrile illness.
Typically seen:
  • Macrocephaly & widening of Sylvian fissures on MRI
  • Episodes of acute encephalopathy w/dystonic crises
  • ↑ urine glutaric acid & 3-OH-glutaric acid
D-2-hydroxyglutaric aciduria
(OMIM 609186)		 D2HGDH ARSymptoms may worsen following febrile illness.Typically seen:
  • Seizures, cardiomyopathy, cognitive regression
  • ↑ urine D-2-hydroxyglutaric acid
May be seen:
  • Subependymal cysts on MRI
  • ↑ blood/CNS lactate
Biotin-thiamine-responsive basal ganglia disease SLC19A3 ARDysarthria & eye mvmt abnormality are common.Typically seen:
  • Encephalopathy
  • Good response to high doses of biotin & thiamine
May be seen:
  • Signal abnormality in the brain stem on MRI
Huntington disease HTT 4ADAtaxia & chorea may also be present.
  • Characteristic MRI feature: caudate head atrophy
  • Parkinsonism common in juvenile form
Chorea-acanthocytosis VPS13A ARDysarthria is common.Typically seen:
  • Onset after 3rd decade (although childhood onset has been reported)
  • Cognitive & behavioral changes
  • Caudate atrophy on MRI (characteristic feature)
  • ↑ creatine kinase & acanthocytes
  • Seizures (in almost half of affected persons)
DRPLA 5 ATN1 ADAtaxia & chorea may also be present.Typically seen:
  • Myoclonic epilepsy, behavioral changes, dementia
  • Atrophic changes in cerebellum & brain stem on MRI
Wilson disease ATP7B ARChorea & dysarthria are common.Typically seen:
  • Tremor, parkinsonism, behavioral changes
  • Liver disease
  • Kayser-Fleischer ring
May be seen:
  • Low serum ceruloplasmin & high urinary copper
NBIA 6See footnote 7.AR, AD, XL
  • Dysarthria is common.
  • Optic atrophy may be present.
  • Hyperintense T2-weighted signal may be observed in basal ganglia on brain MRI.
Typically seen:
  • Parkinsonism & neuropsychiatric abnormalities
  • Brain iron accumulations & (in some cases) accompanying cerebral & cerebellar atrophy on MRI

AD = autosomal dominant; AR = autosomal recessive; Mit = mitochondrial; MOI = mode of inheritance; XL = X-linked

1.

In addition to dystonia and MRI findings of signal abnormality in the basal ganglia

2.

Leigh syndrome, a heterogeneous group of disorders, is associated with pathogenic variants in more than 70 genes (nuclear and mitochondrial).

3.

Pathogenic variants in MT-ND1, MT-ND4, and MT-ND6 account for >90% of cases; pathogenic variants in other mitochondrial genes are also possible.

4.

Huntington disease is caused by an expansion of 36 or more CAG trinucleotide repeats in HTT.

5.

DRPLA = dentatorubral-pallidoluysian atrophy

6.

NBIA = neurodegeneration with brain iron accumulation

7.

NBIA is a heterogeneous group of disorders associated with pathogenic variants in at least ten genes (see Neurodegeneration with Brain Iron Accumulation Disorders Overview).

From: MECR-Related Neurologic Disorder

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