Paediatric radiology
Case TypeClinical Cases
Authors
César Urtasun Iriarte 1, Miguel Barrio Piqueras 1, José Miguel Escudero Fernández 2, Ignacio Delgado Alvárez 2, Élida Vázquez-Méndez 2
Patient7 months, female
A 7-month-old girl presented to the emergency room with tonic spasms following gastroenteritis. She was born to non-consanguineous parents and had a feeding history based on artificial formulas. Examination showed macrocephaly, hypotonia, and asymmetric dystonic posture. MRI was ordered. Urine analysis showed increased glutaric acid (>10000 mmol/mol; normal range 0.6 - 6.6) and 3- hidroxiglutaric (250 mmol/mol; normal range 0 - 5.69).
A brain MRI was performed and showed (Figures 1a and 1b) macrocephaly, reduced operculization and widening of the Sylvian fissures and bilateral temporobasal arachnoid spaces with mild hypoplasia of bilateral temporal lobes, and abnormal T2WI white matter signal (Figures 1b and 1c) suggestive of diffuse and bilateral leukoencephalopathy.
Basal ganglia (predominantly the internal and external pallidum), posterior margin of the thalamus, subthalamus nuclei and substantia nigra displayed an abnormal T2 signal. Atrophy and necrosis of the basal ganglia are seen, suggesting a subacute-chronic evolution, and the restriction suggests exacerbation of the underlying disease. Corpus callosum fibres were spared and no subcortical cysts were observed.
Background
Glutaric aciduria (GA) is an autosomal recessive (AR) neurometabolic disorder characterized by the deficient activity of the enzyme glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid and its metabolites. This condition disrupts the metabolism of lysine, hydroxylysine, and tryptophan. GA is classified into type I (1:100.000 newborns), caused by glutaryl-CoA dehydrogenase deficiency, and type II (1:250.000 newborns), caused by electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase deficiency [1,2].
Clinical perspective
The clinical presentation of GA exhibits significant variability. Type I affected individuals appear healthy at birth but develop symptoms between 3 and 36 months of age. Common manifestations include macrocephaly, hypotonia, developmental delays, and progressive neurological deterioration. Acute encephalopathic episodes can be triggered by infections, fever, and other stressors [2].
In this case, imaging and clinical findings suggested a neurometabolic disorder crisis, and intoxication treatment principles for metabolic diseases were followed (omission of protein intake for 24-48h, L-carnitine supplementation, high-caloric intake, and maintenance of homeostasis via IV fluids). Definitive diagnosis was later reached by genetic analysis (Homozygous variant c.262C>T, in exon 4 of the GCDH gene translatable as glutaryl-CoA enzyme deficiency). The patient follows a low-lysine diet with L-carnitine supplementation and is clinically stable.
Imaging perspective
Imaging plays a pivotal role in diagnosing and assessing GA. Brain MRI is the modality of choice. Diagnostic pearls include [3]:
The involvement of the deep grey matter in combination with the white matter points to a potential neurometabolic disorder or pan-dystrophy.
Outcome
Early detection, and dietary modifications (low-lysine diet and L-carnitine supplementation) along with acute metabolic decompensation treatment (omission of protein intake for 24-48h, L-carnitine supplementation, high-caloric intake, and maintenance of homeostasis via IV fluids) are paramount in GA patients management [1,4] in order to improve its prognosis.
Take-home messages
[1] Severino M (2012) Glutaric Aciduria Type 1. In Rumboldt Z, Castillo M, Huang B, Rossi A (Eds.), Brain Imaging with MRI and CT: An Image Pattern Approach, pp. 33-34. Cambridge: Cambridge University Press.
[2] Bekiesinska-Figatowska M, Duczkowski M, Duczkowska A, Taybert J, Krzywdzinska A, Sykut-Cegielska J (2021) Increasing the spectrum of white matter diseases with tigroid pattern on MRI: glutaric aciduria type 1 - case report. BMC Pediatr 21(1):146. doi: 10.1186/s12887-021-02603-5 (PMID: 33773571)
[3] Ibrahim M, Parmar HA, Hoefling N, Srinivasan A (2014) Inborn errors of metabolism: combining clinical and radiologic clues to solve the mystery. AJR Am J Roentgenol 203(3):W315-27. doi: 10.2214/AJR.13.11154 (PMID: 25148190)
[4] Nunes J, Loureiro S, Carvalho S, Pais RP, Alfaiate C, Faria A, Garcia P, Diogo L (2013) Brain MRI findings as an important diagnostic clue in glutaric aciduria type 1. Neuroradiol J 26(2):155-61. doi: 10.1177/197140091302600204. Epub 2013 May 10 (PMID: 23859237)
URL: | https://eurorad.org/case/18324 |
DOI: | 10.35100/eurorad/case.18324 |
ISSN: | 1563-4086 |
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