Spectrum of movement disorders associated with glutaric aciduria type 1: A study of 16 patients

Abstract

Glutaric aciduria type 1 (GA1) is an autosomal recessive neurometabolic disorder due to glutaryl CoA dehydrogenase deficiency. Comprehensive descriptions of GA1-associated movement disorders are rare. In order to refine the description of the motor phenotype, we prospectively studied 16 consecutive pediatric and adult GA1 patients, focusing on the movement disorders and their time course. In most patients, generalized dystonia, superimposed on baseline axial hypotonia, remained the predominant feature throughout the disease course. With aging, it tended to evolve from mobile to fixed dystonia and to be associated with akinetic-rigid parkinsonism. Prominent orofacial involvement was a consistent feature in GA1 patients with movement disorders, resulting in speech disorders with features of combined hyperkinetic dysarthria and speech apraxia. The types and outcome of movement disorders in this setting should be taken into consideration during rehabilitation and for patient selection and evaluation in therapeutic trials.

Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I — A decade of experience

“…The majority of untreated patients develop striatal injury acutely during catabolic conditions or insidiously between 3 and 36 months of age [7,[12][13][14]. Striatal injury results in a complex movement disorder with predominant dystonia [15,16]. Antidystonic treatment is often unsatisfactory, and life expectancy is limited in severely disabled children [17,18].…”

Rhabdomyolysis, acute renal failure, and cardiac arrest secondary to status dystonicus in a child with glutaric aciduria type I

“…Acute "metabolic stroke" in patients with glutaric aciduria type 1 (GA I, OMIM ID: 231670) affects the basal ganglia, primarily the neostriatum, and can produce severe extrapyramidal movement disorder [1][2][3][4][5]. Rhabdomyolysis has been described in the literature in two previous patients with GA1 [6,7].…”

Diagnosis and management of glutaric aciduria type I – revised recommendations

“…Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia (Hoffmann et al 1991; Kyllerman et al 1994; Heringer et al 2010). With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop (Gitiaux et al 2008). Morbidity and mortality is high in patients who have had a crisis (Kyllerman et al 2004; Kölker et al 2006).…”