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Lai, L.; , .; Gropman, A.L.; Whitehead, M. MR Neuroimaging in Pediatric Inborn Errors of Metabolism. Encyclopedia. Available online: https://encyclopedia.pub/entry/22894 (accessed on 15 July 2025).
Lai L,  , Gropman AL, Whitehead M. MR Neuroimaging in Pediatric Inborn Errors of Metabolism. Encyclopedia. Available at: https://encyclopedia.pub/entry/22894. Accessed July 15, 2025.
Lai, Lillian, , Andrea L. Gropman, Matthew Whitehead. "MR Neuroimaging in Pediatric Inborn Errors of Metabolism" Encyclopedia, https://encyclopedia.pub/entry/22894 (accessed July 15, 2025).
Lai, L., , ., Gropman, A.L., & Whitehead, M. (2022, May 12). MR Neuroimaging in Pediatric Inborn Errors of Metabolism. In Encyclopedia. https://encyclopedia.pub/entry/22894
Lai, Lillian, et al. "MR Neuroimaging in Pediatric Inborn Errors of Metabolism." Encyclopedia. Web. 12 May, 2022.
MR Neuroimaging in Pediatric Inborn Errors of Metabolism
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This entry is adapted from the peer-reviewed paper 10.3390/diagnostics12040861

Inborn errors of metabolism (IEM) are a group of disorders due to functional defects in one or more metabolic pathways that can cause considerable morbidity and death if not diagnosed early.  Prompt diagnosis is important to guide therapeutic measures and reduce or prevent morbidity and death.  Neuroimaging plays an important role in diagnosis and treatment monitoring. Many IEMs present in the neonatal or early infantile period. Newborn metabolic screens do not capture all IEMs, both false negatives and false positive results can occur, and genetic testing may not always detect pathogenic mutations. Imaging is sometimes performed before the newborn screen results are available, and when positive and correctly interpreted, provides a chance for early intervention.  

inborn errors metabolism MRI MRS

1. MRI and MRS for IEM Diagnosis

1.1. MRI

MRI is the imaging modality of choice for the evaluation of the CNS because it provides excellent soft tissue contrast and exceptional multiplanar anatomic detail. Multiple sequences are exploited to detect altered tissue properties in disease, generally improving diagnostic specificity potential when compared to computed tomography (CT) and ultrasound. For instance, MRI sequences such as diffusion weighted imaging (DWI) help characterize edema during acute episodes of encephalopathy. Although MRI protocols are best tailored to the suspected disorder and clinical question, in general, the following sequences are recommended: T1 weighted imaging (T1WI), T2 weighted imaging (T2WI), T2 fluid attenuated inversion recovery (FLAIR) (age > 1 year) or proton density (PD) (age < 1 year), DWI or diffusion tensor imaging (DTI), susceptibility weighted imaging (SWI with preferably with phase assessment capability), arterial spin labeling (ASL) perfusion, and for leukodystrophies, magnetization transfer T1WI [1].
Neuroimaging manifestations vary within and among IEMs, and may range from normal to diffuse, severe CNS disease depending on many factors such as type/severity of pathway defect, amount of toxic byproduct accumulation (if present), maturity of the brain at the time of insult, duration of injury, compensatory mechanisms, and timing of imaging during the disease course. Additionally, certain anatomic structures are selectively vulnerable to energy failure and toxic substrates [2][3]. Some patterns of characteristic brain involvement have been described: amino acid disorders (i.e., MSUD and NKH) predominantly involve white matter tracts; organic acid disorders usually involve deep gray matter; energy production/lactic acidosis disorders may involve both deep grey and white matter [4]. However, these patterns of involvement are nonspecific and may sometimes overlap with each other. An extensive systemic imaging approach of classifying MRI lesions has been covered [2][3][5].

1.2. 1H MRS

1H MRS provides insight into the metabolic status of the brain at the time of imaging and often reveals diagnostic or suggestive metabolic profiles or mechanisms of certain IEMs.
A standard protocol for IEM evaluation may include single voxel spectroscopy (SVS), point resolved spectroscopy (PRESS), short echo time (TE) of 35 ms, repetition time (TR) of 1500 ms, 128 signal averages, and if possible, a longer TE acquisition (e.g., 144 ms if 1.5T or 288 ms if 3T). Voxel placement (2 × 2 × 2 cm default) location is predicated on the appearance of the brain or suspected disorder [1][6][7]. Common regions of interrogation include the cerebral deep gray nuclei and optional additional voxels over the parietal white matter or midline parietal gray matter. Chronic/inactive necrotic, hemorrhagic, and substantially calcific lesions are best avoided.
Metabolite ratios change based on age, with the most dramatic changes in the first three months of life. Familiarity with normal age-related metabolite ratios is crucial for accurate interpretation [1][6][8]. An example short TE single-voxel (SVS) MRS performed at 3T. The major metabolites include N-acetylaspartate (NAA at 2.0 ppm, neuronal metabolite and biomarker for viable neurons or assessment of parenchymal damage); creatine (Cr at 3.0 and 3.9 ppm, includes free creatine and phosphocreatine, marker of energetic reserve); choline (Cho at 3.2 ppm, marker of cellular proliferation from increased membrane turnover and/or inflammation); myo-inositol (mI at 3.5 ppm, glial metabolite, osmolyte, and marker of gliosis and/or neuroinflammation); lactate (Lac at 1.3 ppm, reflects anaerobic glycolysis); lipid/macromolecules (LipMM at 0.9 and 1.3 ppm from -CH3 and -CH2 groups, respectively); and glutamate (Glu at 2–2.5 ppm, excitatory neurotransmitter) and glutamine (Gln at 2–2.5 and 3.6–3.9 ppm, osmolyte and hyperammonia detoxifier) [1][6][8][9].
1H MRS can sometimes be diagnostic for IEMs, particularly intoxication disorders (e.g., amino acid metabolism, urea cycle disorders, and organic acid disorders) as well as disorders of biosynthesis and breakdown of complex molecules (e.g., lysosomal and peroxisomal disorders). These disorders cause accumulation of certain molecules in the brain, which manifest as characteristic peaks and/or peak patterns on spectroscopy. When lactate is sought to support a diagnosis of primary-IEM-related mitochondrial dysfunction, documenting its presence in normal appearing brain tissue is more suggestive of systemic disease than showing lactate in focal lesions with reduced diffusion, which may simply reflect local anaerobic metabolism associated with the lesion itself. Note that a small amount of lactate may be present in normal pre-term infant brains due to underactivity of pyruvate dehydrogenase, but only minimal if any lactate should be visible in term infant brains [1][8].
MRS can also help in the evaluation of leukoencephalopathies, which often present with nonspecific diffuse white matter signal changes. Leukodystrophies that present with demyelination, such as adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), and Krabbe disease, may show increased Cho, mI (demyelination and glial/astrocyte proliferation), decreased NAA (neuronal loss/injury), and increased Lac [5]. Other leukodystrophies such as megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease) or vanishing white matter disease may show a diffuse decrease in metabolites [5].

2. MRI and/or 1H MRS Suggestive of IEMs (in the Appropriate Clinical Context)

Urea Cycle disorders: Urea cycle disorders (UCD) are caused by defects in the conversion of ammonia to urea, resulting in accumulation of ammonia and glutamine (Gln). Gln is osmotically active, leading to diffuse edema in the cerebral cortex and subcortical white matter when in large concentrations. Brain MR findings characteristic to UCD-related hyperammonemia include a central pattern of edema involving the peri-rolandic, peri-insular, and basal ganglia regions, often sparing the thalami, which helps distinguish it from HIE [10][11][12].
MRS shows elevated Glu/Gln peaks between 2 and 2.5 ppm during times of hyperammonemia, and a lactate doublet at 1.3 ppm when mitochondrial function fails to meet metabolic demand [10]. Glu/Gln resonances overlap at 1.5T but are more separable at 3T due to chemical shift dispersion; the peak centered at 2.4 corresponds more to glutamine [9]. There is also a commonly overlooked glx peak produced by alpha protons at 3.75 ppm. MI and Cho are usually reduced in chronic hyperammonemia, findings that can be highly suggestive of an underlying UCD in the correct clinical context [13][14].
Primary Lactic acidosis disorders: In the early stages, mitochondrial disorders with lactic acidosis may show focal edema in the deep gray nuclei, periaqueductal areas, white matter, and/or cerebellar peduncles. Later, more diffuse brain involvement may be seen [4]. Prolonged increased lactate doublet on MRS at 1.3 ppm, while nonspecific, may reflect mitochondrial encephalopathy or a problem with energy production and resultant lactic acidosis. Increased lactic acid may also be present in other IEMs such as organic acid and amino acid disorders [11]. Increased Lac seen in areas of normal brain on MRS can suggest underlying IEM [4][8].
The most well-known and recognized pattern is Leigh syndrome with symmetric deep grey nuclei and/or brainstem involvement on MRI [10]. Leigh syndrome may be due to a broad range of genetic variants in either nuclear or mitochondrial DNA.
Leukoencephalopathy with brainstem and spinal cord involvement with lactate elevation (LBSL), due to a defect in mitochondrial enzyme aspartyl-tRNA synthetase, is another entity, which may present with suggestive imaging findings of extensive white matter involvement concentrated in the brainstem (corticospinal, ascending sensory, pontocerebellar, and trigeminal nerve fibers) and spinal cord (lateral corticospinal tracts and dorsal columns) with variable cerebral white matter involvement (typically corticospinal tracts, corpus callosum, and other cerebral white matter sparing the U-fibers) and elevated Lac in white matter on MRS [15].
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) may also have suggestive imaging features, with patients having non-vascular territorial metabolic stroke-like episodes [10]. Similar to MELAS, POLG-related mitochondrial disorders often cause nonterritorial cortical/subcortical edema/injury; however, perirolandic parenchyma and thalami tend to be more preferentially affected [16].
Molybdenum cofactor deficiency (MCD) and sulfite oxidase deficiency (SOD): These are disorders of sulfur-containing amino acid metabolism involved in the function of the electron transport chain. They may be indistinguishable and overlap with HIE and mitochondrial diseases both clinically and on neuroimaging. Findings that favor MCD/SOD include caudate head involvement (usually spared in HIE), thalamic sparing (often involved in HIE), chronic lesions in a neonate such as necrotic/hemorrhagic basal ganglia lesions (often asymmetric), progressive encephalopathy, facial dysmorphism, intractable seizures, high urine sulfite levels, and decreased uric acid in the serum or urine [10][11][17]. Cytotoxic edema may be present in the striatum and/or cortex/subcortical cerebral white matter with evolution to necrosis and ulegyria without preference for borderzone arterial territories (unlike HIE) [18]. MRS can demonstrate accumulated metabolites such as taurine (3.2–3.4 ppm), S-sulocysteine (3.6 ppm) and cysteine (2.9–3 ppm) as well as elevated Glu/Gln (sulfites inhibit glutamate dehydrogenase), increased Lac, and decreased NAA [11][17]. In addition, Cho tends to be elevated rather than reduced as often seen in acute HIE due to its osmolytic properties [11][19].
Biotin-thiamine responsive basal ganglia disease: SLC19A3 gene mutations cause a Leigh-like phenotype with multifocal progressive cerebral deep gray nuclear lesions (basal ganglia > thalami) that evolve to encephalomalacia, gliosis, and necrosis [20][21][22][23][24]. Cerebral cortex, white matter, brainstem, and cerebellum are less commonly involved [23][24]. MRS may show pyruvate [20].
Lysosomal storage disease: GM2 gangliosidoses, including Tay-Sachs disease and Sandhoff disease, can show characteristic T2 hypointensity in the ventral thalami and T2 hyperintensity in the basal ganglia and dorsal thalami [25]. Krabbe disease may show diffuse thalamic T2 hypointensity extending to the corticospinal tracts, as well as signal abnormalities in the cerebral and cerebellar white matter, especially the dentate hila and posterior cerebral white matter (centrifugal and posteroanterior gradient often with a tigroid pattern) and variable enlargement of the optic nerve and chiasm due to accumulation of globoid cells; MR phenotypes vary with age [4][10][12][26]. Post-contrast enhancement of multiple cranial nerves and the cauda equina is also characteristic. Metachromatic leukodystrophy and Krabbe disease may have overlapping imaging features; however Krabbe disease typically spares the callosal genu and more often involves the internal capsules and brainstem [27]. Neuronal ceroid lipofuscinosis may also demonstrate thalamic T2 hypointensity, with cortical atrophy as another prominent feature [2].
Aicardi–Goutières syndrome (AGS): This is an interferonopathy caused by pathogenic defects in genes that are involved in nucleotide metabolism and/or sensing [28]. Calcifications, white matter disease, and atrophy comprise the classic neuroimaging triad; however, other features correlate with the genotype, including a pseudo-TORCH neonatal presentation (TREX1), diffusely white matter signal abnormality with swelling, atrophy, and calcifications often with an infantile disease onset (RNASEH2B), bilateral striatal necrosis and subacute dystonia usually following infection with or without calcifications (ADAR1), and arterial abnormalities/vascular injury (e.g., moyamoya, aneurysms, stenosis, infarcts, and hemorrhage) (SAMHD1) [28].
Disorders of lipid metabolism: Lipid metabolism disorders such as those involving carnitine palmitoyltransferase (CPT) may have lipid elevation on MRS despite normal neuroimaging, mild brain changes, or nonspecific brain MRI abnormalities [6][13][29].
Disorders of Metal metabolism: Disorders of copper metabolism including Menke’s and Wilson’s disease may have suggestive MR imaging findings. Circle of Willis arterial tortuosity and elongation is nearly universal in Menke’s disease; white matter changes including transient vasogenic temporal white matter edema, vermian hypoplasia, progressive atrophy, and development of subdural fluid collections are additional findings [12]. These neuroimaging manifestations are especially important to recognize in young patients since the characteristic kinky hair of Menke’s disease may not be clinically apparent in the first few months of life [12]. In Wilson’s disease, brain MRI findings are age-dependent; most are normal under 10 years of age, hepatic-disease-related T1 hyperintensity may be present in the globus pallidus ± striatum and/or upper brainstem at mean age 11 years, and T2 hyperintensity may be present at mean age 13 years involving the following regions in descending order of prevalence: putamen (sometimes with central hypointensity), globus pallidus, caudate, thalamus, brainstem [30][31].
Pantothenate kinase associated neurodegeneration (PANK) is a form of neurodegeneration with brain iron accumulation (NBAI) that results in a highly suggestive MRI pattern termed “the eye-of-the-tiger sign”, which is peripheral globus pallidus hypointensity and central hypointensity on T2WI representing iron accumulation with central necrosis [32]. Clinically, extrapyramidal movement disorders develop.

3. MRI and/or 1H MRS Diagnostic Based on Disease Pattern (“Aunt Minnies”)

Maple syrup urine disease (MSUD): MSUD is a rare autosomal recessive disorder caused by defective oxidative decarboxylation of the branched-chain amino acids (BCAAs) valine, isoleucine, and leucine. The accumulation of metabolites in urine leads to the odor resembling maple syrup. Characteristic MRI findings include intramyelinic edema characterized by marked diffusion restriction along myelinated white matter of the cerebrum, cerebellum, and brainstem [10][11][12]. 1H MRS is diagnostic, with a characteristic broadened peak complex at 0.9 ppm that inverts at intermediate TE due to branched chain amino acids and ketoacids [10]. In addition to short TE, a longer echo time MRS is useful to eliminate the overlapping peaks of lipid at 0.9 ppm. A lactate peak (anaerobic glycolysis) and decreased NAA/Cr ratio may also be present.
Nonketotic Hyperglycinemia (NKH) or glycine encephalopathy: NKH shows reduced diffusion in myelinated white matter tracts due to intramyelinic edema and vacuolization (usually involving the internal capsules, brainstem, and cerebellar white matter), with extent of involvement less prominent compared to MSUD [2][6][10][11][12]. Additional findings usually include hypogenesis of the corpus callosum and hypoplasia of the cerebellar vermis [11]. MRS reveals an elevated glycine peak at 3.55 ppm, which is best distinguished from the normal mI peak with intermediate or long echo 1H MRS due to its longer T2 decay [10][11][12].
Phenylketonuria (PKU): PKU is usually diagnosed at newborn screening. PKU may result in elevated phenylalanine in the brain due to deficiency of phenylalanine dehydroxylase, with a characteristic phenylalanine peak at 7.37 ppm on MRS using a short TE [2][10]. MRI may show increased T2 signal in the periventricular and subcortical white matter [10][17].
Glutaric Aciduria Type 1 (GA-I): GA-I is a disorder of lysine, hydroxylysine, and tryptophan catabolism that results in characteristic MRI findings of poorly formed operculum, widened Sylvian fissures and frontotemporal CSF spaces, large cavum septi pellucidi, and basal ganglia lesions [10][11][12]. Supratentorial subdural hematomas may develop over time as a consequence of cerebral atrophy [17][33]. GA-I should be distinguished from glutaric aciduria type II that is caused by the inability to breakdown proteins and fats for energy and may present with underdeveloped frontotemporal lobes and enlarged sylvian fissures, delayed myelination, and hypoplasia of the corpus callosum [34]..
L-2-hydroxyglutaric aciduria (L2HGA): In this disease, there is an accumulation of L-2-hydroxyglutaric acid due to a mitochondrial enzyme gene L2HGDH mutation. MRI typically shows a centropedal pattern of brain involvement with edema within the frontal and subcortical white matter, which progressively becomes more confluent but spares the brainstem. The dentate nuclei and basal ganglia are usually involved, but the thalami are spared [17][35]. Another IEM with centrifugal white matter involvement, Kearns–Sayre syndrome, typically shows calcifications unlike L2HGA. In L2HGA, MRS may reveal decreased NAA and increased mI.
Mucopolysaccharidoses (MPS): MPS are a group of lysosomal storage disorders that demonstrate characteristic though inconstant MR features of enlarged perivascular spaces, cerebral white matter hyperintensity on T2/FLAIR, and ventriculomegaly [12]. Spinal imaging shows a dysostosis multiplex. MRS can demonstrate elevated Cho (gliosis and demyelination) and peaks at 3.6–3.7 ppm from mucopolysaccharides accumulated in the brain [10].
α-Mannosidosis: MRS shows a broadened peak (3.5–3.9 ppm) representing mannose-rich oligosaccharides that can resolve following bone marrow transplant. On MRI, hypomyelination and leukodystrophy are present.
Fucosidosis: MRS may show a broadened peak at 3.8–3.9 ppm attributed to carbohydrate-containing macromolecules, such as mannosidosis. However, there is an additional peak at 1.2 ppm that inverts at intermediate echo time attributable to fructose, which makes the diagnosis [36]. Characteristic MRI abnormalities include hypomyelination with T1 and T2 shortening in the globus pallidus, T2 prolongation in the globus pallidus internal medullary lamina, and callosal thinning [37].
Salla disease: This is a lysosomal disorder causing a defect in sialic acid transport, resulting in elevated N-acetyl neuraminic acid. An elevated peak of the N-acetyl methyl group at 2.0 ppm on MRS may be confused with NAA [38]. This is rare and usually seen in Scandinavian ancestry, with minimal or slow myelination, cerebral subcortical white matter involvement sparing the deep white matter, accelerated iron deposition most pronounced in the globus pallidus, thinning of the corpus callosum, and variable cerebellar atrophy [12][37][38].
X-linked Adrenoleukodystrophy (ALD): This peroxisomal disorder is due to a defect in oxidation of long-chain fatty acids resulting in their accumulation. Lesions usually initiate in the callosal splenium and spread into the forceps major, projectional fibers, and auditory and visual pathway; however, in a minority of situations, they may begin in the callosal genu and extend into the forceps minor and beyond [10][38]. Laminated zones of signal alteration in the involved cerebral areas are characteristic, with reduced diffusion and post-contrast enhancement during active demyelination and inflammation, The addition of X-ALD to newborn screen testing has brought about pre-symptomatic MR screening; these scans require careful scrutiny for early/mild changes with special attention to the corpus callosum [39]. Boys with X-ALD should be monitored with serial MRIs based on consensus guidelines [40]. MRS demonstrates decreased NAA and elevated Cho and mI, findings that can improve after successful stem cell transplant [41][42].
Zellweger syndrome: Peroxisomal function is vital to neuronal migration and organization and myelination [2]. PEX gene defects account for most peroxisomal bioassembly disorders, including the milder phenotype, peroxisome biogenesis disorder-1B (PBD1B) comprising neonatal adrenoleukodystrophy and infantile refsum disease. Characteristic MRI findings of Zellweger syndrome include cortical malformations, germinolytic cysts, white matter abnormalities, and reduced gray and white matter volume [10][11][12]. D-bifunctional protein deficiency caused by a disorder of peroxisomal fatty acid beta-oxidation may manifest similar findings. PBD1B also may have overlapping neuroimaging abnormalities, but lacks the systemic findings (e.g., renal cysts, chondrodysplasia punctata) seen in Zellweger syndrome [2]. Dentate hilar/superior cerebellar peduncle involvement progressing to involve the cerebellar white matter more diffusely, the brainstem, thalami, and cerebrum with a posteroanterior gradient typifies the temporal pattern of PBD1B [43]. MRS may show lipid elevation and findings secondary to hepatocellular dysfunction (increased Glu and Gln, decreased mI) [10][12].
Canavan disease: Canavan disease is due to a deficiency of aspartoacylase, which catalyzes the hydrolysis of NAA and leads to accumulation of NAA [17]. Macrocephaly is typically present but not universal. On MRI, diffuse spongiform changes are present involving the white matter, thalami and globi pallidi but sparing the caudate nuclei and putamina. Reduced diffusion is found in the involved white matter during the active phase of disease. 1H MR spectra is pathognomonic with a markedly increased NAA peak at 2.01 ppm.
Alexander disease: Alexander disease is an astrocytopathy, which similar to Canavan disease, may present as a macrocephalic leukodystrophy. Frontal disease predominance, striatal involvement, thalamic sparing, post-contrast enhancement and lack of restricted diffusion usually distinguish Alexander from Canavan disease [10]. MRS generally shows elevated inositols, and unlike Canavan disease, reduced NAA [10].
Pyruvate dehydrogenase complex (PDHc) deficiency: PDHc deficiency is due to impaired pyruvate to acetyl-coA conversion and lactate accumulation. MRS shows elevated Lac and pyruvate at 2.37 [12]. There are two distinct PDHc deficiency phenotypes, (1) prenatal onset with destructive changes and brain malformations such as dysgenesis of the corpus callosum and neuronal migrational abnormalities, and (2) postnatal onset energy failure with Leigh disease [10][12].
Succinate dehydrogenase (SDH) deficiency: Absent or insufficient oxidation of succinate to fumarate and electron delivery to the respiratory chain results in significantly elevated Lac levels and a specific succinate peak that can be detected at 2.4 ppm in affected white matter [44]. MRI shows involvement of the cerebral white matter (sparing the U-fibers and corpus callosum outer fibers), corticospinal tracts, middle cerebellar peduncles, spinal cord, and specific thalamic regions [44].
Creatine deficiency syndromes: These include disorders of biosynthesis and transport of creatine, including guanidinoacetate methyltransferase deficiency (GAMT gene) [45] and L-arginine-glycine amidinotransferase deficiency (GATM gene) [46], and creatine transporter deficiencies (an X-linked disorder with SLC6A8 gene mutations) [14][47]. Creatine is essential for neuronal energy storage and transmission [8]. MRI is usually either normal or shows mild, nonspecific changes such as volume loss. However, 1H MRS shows the diagnostic markedly reduced or completely absent Cr peaks at 3 and 3.9 ppm [10][13][14]. An abnormal broad guanidinoacetate peak is present in patients with GAMT gene defects at 3.78 ppm [11].
Galactosemia: Galactosemia is due to a deficiency of galactose-1-phosphate enzyme and results in the accumulation of galactose-1-phosphate and galactitol. A galactitol peak at 3.7 ppm (doublet at short TE; peak inversion at intermediate TE) and reduced mI are characteristic on MRS [2][13]. MRI may be normal or show nonspecific abnormalities such as multifocal or confluent frontoparietal white matter lesions to diffuse brain edema [48].
Congenital disorder of glycosylation Type 1a (CDG-1a): CDGs are genetically heterogenous autosomal disorders caused by abnormal glycosylation of N-linked oligosaccharides. CDG-1a is the most common form and is an early onset neurodegenerative disorder with selective hindbrain involvement and variable clinical presentation. Key MR findings are diffuse cerebellar volume loss with diffuse cerebellar T2/FLAIR hyperintense signal [49][50]. Other findings include progressive volume loss of the cerebellum and pons, as well as the supratentorial white matter [49]. MRS findings include reduced NAA/Cr ratios and increased mI [49].
Muscular dystrophy–dystroglycanopathy (congenital with brain and eye anomalies): This is a heterogenous group of neuromuscular disorders due to reduced glycosylation of alpha-dystroglycan with somewhat poor phenotype–genotype correlation. Characteristic neuroimaging findings include extensive malformations of cortical development of various types, especially cobblestone lissencephaly, white matter disease, hydrocephalus, and brainstem and variable cerebellar hypoplasia/dysgenesis [12]. Peripheral cystic appearing areas along the cerebellar surface are typical findings but may not be visible without high resolution sequences. Peculiar brainstem deformities are often present in more severe forms, including a kinked, z-shape brainstem, midline pontine clefting, and bulbous appearance of the midbrain, among others [12]. Ocular abnormalities are variable but frequent; although a formal ophthalmologic assessment may be necessary for detection, many are visible on brain MRI, for instance persistent fetal vasculature and microphthalmia.

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