|Year : 2016 | Volume
| Issue : 6 | Page : 756-757
Glutaric aciduria type-I: A potentially treatable and easily diagnosable neurometabolic disorder
Department of Pediatrics, JNMC, KLEU, Belagavi, Karnataka, India
|Date of Web Publication||16-Nov-2016|
JNMC, KLEU, Belagavi, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kamate M. Glutaric aciduria type-I: A potentially treatable and easily diagnosable neurometabolic disorder. Med J DY Patil Univ 2016;9:756-7
|How to cite this URL:|
Kamate M. Glutaric aciduria type-I: A potentially treatable and easily diagnosable neurometabolic disorder. Med J DY Patil Univ [serial online] 2016 [cited 2021 Apr 20];9:756-7. Available from: https://www.mjdrdypu.org/text.asp?2016/9/6/756/194223
Although individually rare, collectively inborn errors of metabolism (IEM) are not uncommon causes of various neurological syndromes in children. Diagnosis of IEM needs specialized investigations such as gas chromatography/mass spectroscometry and tandem mass spectrometry which are not widely available in developing countries like India.  Enzymatic analysis and genetic analysis for confirmation are very expensive and not widely available for most IEM in India. A few of the metabolic disorders have characteristic clinical and neuro-imaging features, which when seen almost clinches the diagnosis.  Glutaric aciduria type I (GA-I) is one such condition and it is one of the treatable IEM.  The most striking finding on brain imaging is the presence of very wide cerebrospinal fluid (CSF) spaces anterior to the temporal lobes and within the sylvian fissures. Widening of the sylvian fissures is a very characteristic finding in GA-I. GA-I is caused by glutaryl-CoA dehydrogenase deficiency.  In developing countries like India, very few cases of this disorder have been reported mainly in the form of isolated case reports and series , without much details on the treatment, prognosis, and outcome.
Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and subsequently, dystonia. Patients develop normally until the initial neurologic presentation, which may be at 2-37 months (mean-14 months). Most children have macrocephaly on examination which can be an important clinical clue for GA-I. Recovery from acute episode is slow and incomplete with developmental delay, dystonia, or dyskinesia as sequelae.  Because of the lack of specialized centers to deal with neurometablic disorders and due to lack of knowledge in developing countries, many cases are being misdiagnosed or may be on inappropriate treatment like has been the case reported in this issue of the journal.
Neuroimaging findings in GA-I may range from a complete lack of operculation with gross hypoplasia of the temporal lobes to widening of sylvian fissures in proportion to the prominence of other extracerebral CSF spaces. This gives the characteristic "bat-wings" appearance. Extra cerebral fluid collections other than those anterior to the temporal lobes include subdural collection or bilateral frontoparietal subdural hematomas. The acute presentation is often accompanied by an abnormal T2 signal in the caudate heads and putamen bilaterally.  The finding of very widely open opercula suggests GA-I and if combined with basal ganglia lesions is almost pathognomonic, especially in a child with macrocephaly.  A clinical diagnosis should be followed by attempts to have genetic confirmation so as to enable fool-proof prenatal diagnosis.
During the last three decades, attempts have been made to establish and optimize therapy for GA-I. Many recommendations on diagnosis and management have been published and revised in the recent past. , Treatment consists of carnitine supplementation along with low protein diet, especially deficient in lysine and tryptophan and careful management of these children during stressful episodes. The role of riboflavin supplementation is not very clear. Because of nonavailability of special diets, many of the patients in developing countries are advised nonspecific protein-restricted diet, carnitine supplementation, and emergency-care management measures. This treatment strategy has considerably reduced the frequency of acute encephalopathic crises and thus morbidity and mortality in early-diagnosed patients. Therefore, GA-I deficiency is now considered to be a treatable neurometabolic disorder. Diagnosis of a condition like GA-I is important as it is an autosomal recessive disorder and there is 25% chance of recurrence in future pregnancies. The condition can worsen with infections in future if proper precautions are not taken. It is also important for counseling parents regarding the prognosis and avoid unnecessary interventions.
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