Table 3b.

Metabolic Disorders with Overlapping MRI Findings in the Differential Diagnosis of SLC39A8-CDG

GeneDisorder 1Clinical Characteristics
MRI findingsClinical features
ABHD12 PHARC syndrome (OMIM 612674)Cerebellar atrophy
  • Ataxia
  • Cataracts
  • Hearing loss
  • Neurodegeneration
  • Retinitis pigmentosa
ALDH18A1 Delta-1-pyrroline-5-carboxylate synthetase deficiency 2Cerebellar atrophy
  • Cataracts
  • Cutis laxa
  • DD/ID
  • Faltering growth
  • Hypotonia
  • Joint hyperlaxity
  • Microcephaly
  • Short stature
ALDH5A1 Succinic semialdehyde dehydrogenase deficiency
  • Abnormalities of myelination
  • Cerebellar atrophy
  • Hyperintensity of T1-weighted signals in globus pallidus
  • Ataxia
  • DD
  • Epilepsy
  • Hyporeflexia
  • Hypotonia
FA2H Fatty acid hydroxylase-associated neurodegeneration
  • Confluent periventricular white matter abnormalities
  • Iron accumulation
  • Profound pontocerebellar atrophy
  • Cognitive decline
  • Optic atrophy
  • Progressive spastic paraparesis & dysmetria
  • Xeroderma
GCDH Glutaric acidemia type 1
  • Cerebellar atrophy
  • Cortical atrophy
  • Progressive disturbance of myelination
  • Signal changes &/or atrophy of basal ganglia
  • Striatal injury spreading in dorsoventral direction
  • Acute brain injury assoc w/infections
  • Choreoathetosis
  • Progressive dystonic cerebral palsy
L2HGDH L-2-hydroxyglutaric aciduria (OMIM 236792)
  • ↑ signal density of dentate nuclei & globi pallidi on T2-weighted images
  • Cerebellar atrophy
  • Leukoencephalopathy
  • Variety of neurologic malignancies
  • Progressive ataxia
  • DD/ID
  • Seizures
  • Spasticity
MVK Mevalonate kinase deficiency (OMIM 610377)Cerebellar atrophy
  • Ataxia
  • Autoinflammation
  • Dysmorphic features
  • Faltering growth
  • Hypotonia
  • ID
PLA2G6 Infantile neuroaxonal dystrophy, NBIA (See PLA2G6-Associated Neurodegeneration.)
  • Cerebellar atrophy
  • Hypointensities in globus pallidus & substantial nigra
  • Signal hyperintensity in cerebellar cortex
  • Cerebellar ataxia
  • Chronic denervation
  • Hypotonia
  • Progression to spastic tetraplegia
  • Progressive motor & cognitive deterioration
  • Visual disturbances
See footnote 3.Leigh syndrome (See Mitochondrial Disorders Overview & Nuclear Gene-Encoded Leigh Syndrome Spectrum Overview.)Symmetrical ↑ signal density of basal ganglia, esp putamina & globi pallidi, on T2-weighted imagesProgressive neurologic & motor decline

DD = developmental delay; ID = intellectual disability; NBIA = neurodegeneration with brain iron accumulation; PHARC = polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract

1.

With the exception of delta-1-pyrroline-5-carboxylate synthetase deficiency (which can be inherited in either an autosomal dominant or autosomal recessive manner) and Leigh syndrome (which can be inherited in an autosomal recessive, autosomal dominant, X-linked, or maternal manner), the disorders in Table 3b are inherited in an autosomal recessive manner.

2.
3.

Many genes (nuclear and mitochondrial) are known to be associated with Leigh syndrome.

From: SLC39A8-CDG

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