Classic Imaging Characteristics of a Clinically Symptomatic Glutaric Aciduria Type I in A female infant- A Case Report

The patient was an 8month old female infant who presented with poor appetite, fever, and generalized tonic clonic seizures and dyskinesia. There was a background delayed motor development and failure to thrive. On examination she was irritable and mildly dehydrated. She was unable to sit even with support, demonstrated brisk reflexes, spastic muscle tone and dystonia. There was positive consanguinity. The patient was born of healthy parents, and also had a healthy brother. She was a product of normal spontaneous vaginal delivery without any prenatal or perinatal complications.

She had an initial computed tomography (CT) scan at presentation. The showed bilateral widening of subarachnoid space along the frontal convexity, and the space anterior to the temporal poles and sylvian fissures (Figure 1). The patient later had magnetic resonance imaging (MRI) within 24hours of presentation. The MRI confirmed the previous CT findings, and also showed diffuse FLAIR/T2 hyperintensity of the deep white matter, caudate nucleus and lentiform nucleus. Similar signal changes were noted in the substantia nigra and dentate nuclei (Figure 2).

She eventually had a genetic assay which identified a heterozygous likely pathogenic variant and heterozygous variant of uncertain significance in the GCDH gene, which were suggestive of autosomal recessive Glutaric aciduria type I.

Glutaric aciduria type I (GA-1) is a rare genetic autosomal recessive disorder belonging to a group of cerebral organic acid disorders. There is deficiency of the glutaryl-coenzyme A (CoA) dehydrogenase, with resultant inability to catabolise amino acids: L-lysine, L-tryptophan and L-hydroxylysine. Glutaric acid, 3-hydroxyglutaric acid, and glutarylcarnitine thus become heavily accumulated within the brain and other body fluids [1,2]. Consanguinity is a known risk factor for GA-1 and has a disease prevalence of about 1:100000 newborns [2-4].

Diagnosis is confirmed by localisation of two disease linked GCDH gene mutations or grossly reduced activity of the GCDH in skin fibroblasts or in leucocytes to less than thirty percent [2]. At presentation the affected infants are often hypotonic and irritable, with some abnormal movements. There is usually a preceding febrile illness with clinical signs of encephalopathy, mimicking a viral illness [2], just as demonstrated in the index case. Macrocephaly has been documented as a common presentation or later in the course of the disease [1,2]. This is however not yet seen in this case, probably due to age. GA-1 had been documented to mimic other central nervous system abnormalities, thus high clinical suspicion and neuroimaging is of enormous value to arrive at a diagnosis [5].

MRI has been shown has the mainstay of imaging in the diagnostic management of GA-1 [4]. The index case presented with classic imaging features of GA-1 as previously reported by severe publications. This patient demonstrated bilateral symmetrical diffuse abnormal T2/FLAIR hyperintense signals in the deep white matter, caudate nucleus, lentiform nucleus, substantia nigra and dentate nucleus [6-9]. Mariasavina Severino was however able to note some variations from the index case and other previously reported imaging findings, such as less or non-affectation of the caudate nuclei, and occasional affectation of the thalamus [9].

Andrea Righini et al reported a GA-1 in a female neonate from a consanguineous marriage. An initial 22-week prenatal MRI raised a suspicion of the diagnosis, which was eventually confirmed through a neonatal MRI and laboratory assays. The mother had a prior transabdominal ultrasound which showed a widening of the supracerebellar cistern and thus raised the suspicion of more serious intracranial structural abnormality [3]. Widening of the supracerebellar cistern was similarly shown in the index case (Figure 3).

Despite the rarity of glutaric aciduria type I, the presence of classic clinical signs of encephalopathy preceded by febrile illness, should raise the suspicion of its possibility, and a neuroimaging preferably MRI should be requested.

None.

None declared by each of the authors.

Consent obtained from the parents of the patient, having been assured of complete confidentiality.

Each of the authors substantially contributed to the conceptualization, design, acquisition of data and analysis/ interpretation of the acquired patient’s data for the purpose of this publication. They all have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

1. Singer HS, Mink JW, Gilbert DL, Jankovic J (2016) Inherited Metabolic Disorders with Associated Movement Abnormalities. In: Movement Disorders in Childhood, pp. 337-407.
2. Kölker S (2014) Organic Acid Disorders. In: Encyclopedia of the Neurological Sciences. Elsevier, pp. 688-693.
3. Righini A, Fiori L, Parazzini C, Doneda C, Arrigoni F, et al. (2010) Early Prenatal Magnetic Resonance Imaging of Glutaric Aciduria Type 1: Case Report. J Comput Assist Tomogr 34(3): 446-448.
4. Baba Y, Kwong Y (2012) Glutaric aciduria type 1.
5. Rajani H, Grover SB, Antil N, Katyan A (2018) A case of mistaken identity: Glutaric aciduria type I masquerading as postmeningitic hydrocephalus. J Clin Imaging Sci 8: 50.
6. Desai NK, Runge VM, Crisp DE, Crisp MB, Gill Naul L (2003) Magnetic Resonance Imaging of the Brain in Glutaric Acidemia Type I. Investig Radiol 38(8): 489-496.
7. Oguz KK, Ozturk A, Cila A (2005) Diffusion-weighted MR imaging and MR spectroscopy in glutaric aciduria type 1. Neuroradiology 47(3): 229-234.
8. Twomey EL, Naughten ER, Donoghue VB, Ryan S (2003) Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol 33(12): 823-830.
9. Severino M (2010) Glutaric aciduria type 1. Brain Imaging with MRI and CT: An Image Pattern Approach, Cambridge University Press, pp. 33-34.