Elsevier

Brain and Development

Volume 21, Issue 1, January 1999, Pages 24-29
Brain and Development

Original article
18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in type IV 3-methylglutaconic aciduria: clinical and MRI correlations

https://doi.org/10.1016/S0387-7604(98)00064-3Get rights and content

Abstract

The clinical, 18fluorodeoxyglucose positron emission tomography (18FDG PET) and the magnetic resonance imaging (MRI) brain scan characteristics of four patients diagnosed to have 3-methylglutaconic aciduria were reviewed retrospectively. The disease has a characteristic clinical pattern. The initial presentations were developmental delay, hypotonia, and severe failure to thrive. Later, progressive encephalopathy with rigidity and quadriparesis were observed, followed by severe dystonia and choreoathetosis. Finally, the patients became severely demented and bedridden. The 18FDG PET scans showed progressive disease, explaining the neurological status. It could be classified into three stages. Stage I: absent 18FDG uptake in the heads of the caudate, mild decreased thalamic and cerebellar metabolism. Stage II: absent uptake in the anterior half and posterior quarter of the putamina, mild-moderate decreased uptake in the cerebral cortex more prominently in the parieto-temporal lobes. Progressive decreased thalamic and cerebellar uptake. Stage III: absent uptake in the putamina and severe decreased cortical uptake consistent with brain atrophy and further decrease uptake in the cerebellum. The presence of both structural and functional changes in the brain, demonstrated by the combined use of MRI and 18FDG PET scan, with good clinical correlation, make the two techniques complementary in the imaging evaluation of 3-methylglutaconic aciduria.

Introduction

3-Methylglutaconic (3-MGC) aciduria is the metabolic landmark of a heterogenous group of disorders [1]. Patients excrete varying amounts of 3-methylglutaconic acid and 3-methylglutaric acid in the urine. One known source of 3-methylglutaconic acid is in the catabolic pathway of l-leucine [2]; however, in other subtypes of the disease, the exact metabolic disorder leading to the excess 3-methylglutaconic acid is unknown. Four different phenotypes, differing in their clinical presentations, have been described [3]. Type I, an autosomal recessive disorder manifested by speech impairment, is due to deficiency of 3-methylglutaconyl-CoA hydratase (EC 4.2.1.18) 4, 5, 6, 7. Type II, an X-linked form, is characterized by cardiomyopathy, skeletal myopathy and recurrent infections, with normal cognitive development [8]. Type III, commonly seen in Iraqi Jews, presents with progressive encephalopathy of varying severity, optic atrophy, movement disorders and spastic paraplegia 1, 2, 9, 10, 11, 12, 13. A distinct phenotype, called Costeff syndrome or optic atrophy plus, a subclass of type III, is a non-progressive encephalopathy characterized by pyramidal and extrapyramidal signs, ataxia and early optic atrophy 14, 15, 16, 17. In types II and III, the elevation of methylglutaconic acid and 3-methylglutaric acid in the urine are modest. Finally, type IV is associated with severe psychomotor retardation and cerebellar dysgenesis [1].

In type I, the 3-methylglutaconyl-CoA hydratase enzyme is deficient, resulting in an increased excretion of 3-methylglutaconic acid. However, the activity of this enzyme is normal, in the other types and the development of abnormal 3-methylglutaconic acid levels is attributed either to a defect in the cholesterol or ubiquinone synthesis, the mitochondrial ATP synthesis [18]or to mitochondrial respiratory chain defects [19].

We present the functional brain imaging using 18fluorodeoxyglucose positron emission tomography (18FDG PET) brain scans and correlate the findings with the anatomical studies (magnetic resonance imaging (MRI)) and the neurological status in four pediatric patients with type IV 3-methylglutaconic aciduria.

Section snippets

Materials and methods

The King Faisal Specialist Hospital and Research Centre (KFSH and RC) is a tertiary care referral centre with facilities for the management of diverse metabolic disorders. Our files contain the data of approximately 2000 patients with different confirmed congenital metabolic disorders, out of which twenty are recorded to have 3-methylglutaconic aciduria. The diagnosis of this disorder is based on the identification of abnormal amounts of 3-methylglutaconic acid and 3-methylglutaric acid in the

Clinical data

All patients were born from consanguineous parents and the age of onset of the clinically apparent signs and symptoms varied between 6 months and 1 year. The disease showed a characteristic neurological pattern, initially presenting with developmental delay and loss of milestones in conjunction with severe failure to thrive and hypotonia. Later, progressive encephalopathy, rigidity and quadriparetic or quadriplegic posturing ensued. Deep tendon reflexes were increased and Babinski or ankle

Discussion

This report describes the appearance of the 18FDG PET brain scan of four patients with 3-methylglutaconic aciduria with correlative structural changes and clinical findings. All patients were Saudi, from consanguineous parents, and all came from the southern province of the country. The families were not related by tribal origin.

Most patients with 3-methylglutaconic aciduria have no etiology. Four types of the disease are known 3, 23. Our patients belong to type IV of the disease. Its presence

Acknowledgements

The authors are grateful to Dr. Sultan Al-Sedairy, Executive Director of the Research Centre, King Faisal Specialist Hospital and Research Centre, for his support of this work. Part of this study was supported by the grant provided by Sheikh Rafik Al-Hariri (#85–0030).

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