Naslov
New symptomatic patients with glutaric aciduria type 3: further evidence of high prevalence of the c.1006C>T (p.Arg336Trp) mutation

Autori
Škaričić, Ana ; Zekušić, Marija ; Fumić, Ksenija ; Bilić, Karmen ; Petković Ramadža, Danijela ; Sarnavka, Vladimir ; Šuman Šimić, Andrej ; Zschocke, Johannes ; Barić, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Journal of Inherited Metabolic Disease, (2016) Volume 39, Suppl.1 / - , 2016, S1-S34

Skup
Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2016

Mjesto i datum
Rim, Italija, 06.09.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Glutaric aciduria type 3

Sažetak
Background: Glutaric aciduria type 3 (GA3) is an autosomal recessive disorder caused by mitochondrial succinate-hydroxymethylglutarate CoA-transferase deficiency. It is characterised by increased persistent, isolated excretion of glutaric acid. There is no distinctive phenotype associated with this disorder. The diagnosis is established by excluding other causes of glutaric aciduria and by gene analysis. Case report: Patient 1 presented at the age of 15 months with recurrent vomiting, hypotonia, ataxia, left abducens paresis and symmetrical patchy white matter changes on brain MRI mimicking postvaccinal encephalopathy. She recovered completely. Patient 2 experienced episodes of agitation and unresponsiveness lasting 2 hours during 3 consecutive nights at the age of 12 months. At the age of 3 years he had signs of attention deficit hyperactivity disorder. In both families parents were unrelated. Results: Organic acid analysis showed elevated urinary excretion of glutaric acid in both patients ranging from 39-98 mmol/mol of creatinine in patient 1 and from 90-133 mmol/mol of creatinine in patient 2 (N<10). Glutaconic and 3-OH glutaric acid were found in traces. Acylcarnitine profiles were normal. Genetic analysis of the coding exons and adjacent intron regions of the succynil-CoA:glutarate- CoA transferase (SUGCT) gene identified c.1006C>T (p.Arg336Trp) mutation in a homozygous state in both patients. Discussion: Our cases suggest that under certain circumstances GA3 may not be a benign condition, as indicated by encephalopathic crises experienced by the first reported patient more than 20 years ago after the first description. The c.1006C>T mutation is known to be causing GA3. Its appearance on four unrelated alleles in our patients points to its high frequency in different populations and possible hot spot of the SUGCT gene. More information and additional haplotype analysis are needed for a more accurate conclusion.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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