Long term follow-up in GAMT deficiency - Correlation of therapy regimen, biochemical and brain proton MR spectroscopy data.

GAMT deficiency is a rare autosomal recessive disease within the group of cerebral creatine deficiency syndromes. Cerebral creatine depletion and accumulation of guanidinoacetate (GAA) lead to clinical presentation with intellectual disability, seizures, speech disturbances and movement disorders. Treatment consists of daily creatine supplementation to increase cerebral creatine, reduction of arginine intake and supplementation of ornithine for reduction of toxic GAA levels.

Preemptive screening of DPYD as part of clinical practice: high prevalence of a novel exon 4 deletion in the Finnish population.

Capecitabine is a fluoropyrimidine that is widely used as a cancer drug for the treatment of patients with a variety of cancers. Unfortunately, early onset, severe or life-threatening toxicity is observed in 19-32% of patients treated with capecitabine and 5FU. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of 5FU and a DPD deficiency has been shown to be a major determinant of severe fluoropyrimidine-associated toxicity.

Functional analysis of thirty-four suspected pathogenic missense variants in ALDH5A1 gene associated with succinic semialdehyde dehydrogenase deficiency.

Deficiency of succinate semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5a1 (ALDH5A1), OMIM 271980, 610045), the second enzyme of GABA degradation, represents a rare autosomal-recessively inherited disorder which manifests metabolically as gamma-hydroxybutyric aciduria. The neurological phenotype includes intellectual disability, autism spectrum, epilepsy and sleep and behavior disturbances. Approximately 70 variants have been reported in the ALDH5A1 gene, half of them being missense variants.

Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic.

Between July of 2012 and December of 2014, 39 patients were enrolled prospectively to investigate the prevalence of glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None of them had GLUT1 deficiency. All patients seen in the same clinic within the same period were reviewed retrospectively.

Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.

Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features.

Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity.

We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase-the hydrolysis of N-acetyl-l-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells.

Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria.

Detection of variants in SLC6A8 and functional analysis of unclassified missense variants.

Creatine transporter deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. Currently, 38 pathogenic, including 15 missense variants, are reported. In this study, we report 33 novel, including 6 missense variants.