Nikolas Boy

Severe Acute Subdural Hemorrhage in a Patient With Glutaric Aciduria Type I After Minor Head Trauma A Case Report

Glutaric aciduria type I is a rare metabolic disorder caused by deficiency of glutaryl-coenzyme A dehydrogenase. Chronic subdural hematomas have been reported in glutaric aciduria type I and are considered as important differential diagnosis of nonaccidental head trauma. However, chronic subdural hematomas are usually thought to remain clinically silent in these patients. Here we report on a hitherto asymptomatic glutaric aciduria type I patient who developed severe, acute subdural hemorrhage after minor accidental head injury at age 23 months. Computed tomography confirmed significant mass effect on the brain necessitating decompressive hemicraniectomy. Subdural hemorrhage caused large hypoxic lesions of the cerebral cortex and subcortical regions resulting in spastic tetraplegia, dystonia, and loss of developmental milestones. This report emphasizes that acute subdural hemorrhage may be a life-threatening complication in glutaric aciduria type I patients after minor head trauma and should be considered in those patients presenting with neurologic deterioration after accidental head injury.

A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I

BackgroundGlutaric aciduria type I (GA-I) is an inherited metabolic disease due to deficiency of glutaryl-CoA dehydrogenase (GCDH). Cognitive functions are generally thought to be spared, but have not yet been studied in detail.MethodsThirty patients detected by newborn screening (n = 13), high-risk screening (n = 3) or targeted metabolic testing (n = 14) were studied for simple reaction time (SRT), continuous performance (CP), visual working memory (VWM), visual-motor coordination (Tracking) and visual search (VS). Dystonia (n = 13 patients) was categorized using the Barry-Albright-Dystonia Scale (BADS). Patients were compared with 196 healthy controls. Developmental functions of cognitive performances were analysed using a negative exponential function model.ResultsBADS scores correlated with speed tests but not with tests measuring stability or higher cognitive functions without time constraints. Developmental functions of GA-I patients significantly differed from controls for SRT and VS but not for VWM and showed obvious trends for CP and Tracking. Dystonic patients were slower in SRT and CP but reached their asymptote of performance similar to asymptomatic patients and controls in all tests. Asymptomatic patients did not differ from controls, except showing significantly better results in Tracking and a trend for slower reactions in visual search. Data across all age groups of patients and controls fitted well to a model of negative exponential development.ConclusionsDystonic patients predominantly showed motor speed impairment, whereas performance improved with higher cognitive load. Patients without motor symptoms did not differ from controls. Developmental functions of cognitive performances were similar in patients and controls. Performance in tests with higher cognitive demand might be preserved in GA-I, even in patients with striatal degeneration.

Organic acidurias in adults: late complications and management

Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids (“organic acids”) and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry-based newborn screening programmes, in particular for isovaleric aciduria and glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary treatment with low protein intake or reduced intake of the precursor amino acid(s), carnitine supplementation, cofactor treatment (in responsive patients) and nonadsorbable antibiotics is commonly used for maintenance treatment. Emergency treatment options with high carbohydrate/glucose intake, pharmacological and extracorporeal detoxification of accumulating toxic metabolites for intensified therapy during threatening episodes exist. Diagnostic and therapeutic measures have improved survival and overall outcome in individuals with OADs. However, it has become increasingly evident that the manifestation of late disease complications cannot be reliably predicted and prevented. Conventional metabolic treatment often fails to prevent irreversible organ dysfunction with increasing age, even if patients are considered to be “metabolically stable”. This has challenged our understanding of OADs and has elicited the discussion on optimized therapy, including (early) organ transplantation, and long-term care.

Newborn screening: A disease-changing intervention for glutaric aciduria type 1: Newborn Screening for GA1

Untreated individuals with glutaric aciduria type 1 (GA1) commonly present with a complex, predominantly dystonic movement disorder (MD) following acute or insidious onset striatal damage. Implementation of GA1 into newborn screening (NBS) programs has improved the short‐term outcome. It remains unclear, however, whether NBS changes the long‐term outcome and which variables are predictive.

Age-Related Changes and Reference Values of Bicaudate Ratio and Sagittal Brainstem Diameters on MRI

&NA; Cranial magnetic resonance imaging (MRI) plays an important role in the diagnosis of neurometabolic diseases, and, in addition, temporal patterns of signal and volume changes allow insight into the underlying pathogenesis. While assessment of volume changes by visual inspection is subjective, volumetric approaches are often not feasible with rare neurometabolic diseases, where MRIs are often acquired with different scanners and protocols. Linear surrogate parameters of brain volume, for example, the bicaudate ratio, present a robust alternative that can be derived from standard imaging sequences. Due to the continuing postnatal brain and skull development and later brain involution, it is, however, necessary to compare patient values with age age‐adapted normal values. In this article, we present age‐dependent normal values derived from 993 standard scans of patients with normal MRI findings (age range: 0‐80 years; mean = 19.9; median = 12.8 years) for bicaudate ratio as a measure of global supratentorial volume, as well as the maximal anteroposterior diameters of mesencephalon, pons, and medulla oblongata as parameters of brainstem volume. The provided data allow quantitative, objective assessment of brain volume changes instead of the usually performed visual and therefore subjective assessment.

Arachnoid Cysts in Glutaric Aciduria Type I (GA-I)

Abstract Glutaric aciduria type I (GA-I) is a rare inherited metabolic disease caused by deficiency of glutaryl-CoA dehydrogenase located in the catabolic pathways of l -lysine, l -hydroxylysine and l -tryptophan. The enzymatic defect results in elevated concentrations of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine in body tissues. Neuropathophysiologic concepts involve disturbance of brain energy metabolism and neurotransmission. Untreated patients are at increased risk for striatal damage and consequent severe neurologic disease. Metabolic treatment is effective and improves neurologic outcome in early diagnosed individuals. Extrastriatal abnormalities frequently occur in all GA-I patients. Bilateral temporal fluid collections, most likely due to frontotemporal hypoplasia, are a characteristic neuroradiologic finding and have been classified (but rarely verified) as bilateral arachnoid cysts (AC). However, the true risk for development of bilateral AC in GA-I is still unknown.