Excess of ammonia causes neurological dysfunction ranging from cognitive impairment to tremor, ataxia, seizures, coma and death. The brain is especially vulnerable to ammonia as it readily crosses the blood-brain barrier in its gaseous form, NH3, and rapidly saturates its principal removal pathway located in astrocytes. Rangroo Thrane and colleagues used a combination of two-photon imaging […]
Posts Categorized: Part 08: AMINO ACIDS
Neurocognitive functioning in adults with PKU
Weglage et al. investigated 57 adult patients with early-treated classical PKU (mean age 31 years) and 46 healthy controls, matched for age and socioeconomic status. MRI brain and evaluation for IQ, as well as for attention and information-processing were performed in all patients and controls. Neuropsychological assessments and MRI were repeated at a five-year-follow up. Over […]
Long-term BH4 responsive PKU patients
There are no established criteria for the identification of patients with phenylketonuria who are long-term BH4 responsive. Hennermann et al. reported that, based on their cohort of patients, long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. The most predictive […]
Lysosomal Lysine/Arginine Transporter Identified
In a forward genetic screen in C. elegans, Liu et al. identified LAAT-1, and its human counterpart PQLC2 as the lysosomal lysine/arginine transporter. Without this transporter, lysosomes become filled with arginine and lysine and this can cause cell death. Mutations in PQLC2 have not yet been identified in humans with lysosomal disorders. Liu B, Du […]
Liver-targeted gene therapy in PKU mice: neurogenic amines & neuropsych function
Aminergic deficit is one of the abnormalities found in the brain of hyperphenylalaninemic patients and a mouse model of PKU. Liver-targeted gene therapy has been previously reported to correct hyperphenylalaninemia and concomitant behavioral recovery in PKU mice. In this study Yagi et al. provide evidence that the functional recovery is mediated by reversal of the […]
New disorder of the methionine cycle
Bjursell MK, Blom HJ, Cayuela JA, Engvall ML, Lesko N, Balasubramaniam S,Brandberg G, Halldin M, Falkenberg M, Jakobs C, Smith D, Struys E, von Döbeln U, Gustafsson CM, Lundeberg J, Wedell A. Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function. Am J Hum Genet. 2011 Sep 28. PubMed PMID:21963049. Phenotype […]
Pathophysiology of UCDs
Ammonia accumulation in urea cycle defects (UCDs) leads to several cellular dysfunctions such as amino acid disturbances and disrupted neurotransmitter signaling (reviewed in Braissant et al, 2010, Mol Genet Metab 100 Suppl 1:S3-S12). Also, the pathophysiology of UCDs does not simply involve ammonia, and this is clinically supported by the fact that specific clinical features […]
Sapropterin and stability of blood phenylalanine in PKU
Variability in blood phenylalanine levels is inversely correlated with IQ and was recently shown to be a better predictor of IQ in early and continuously treated patients with PKU than mean blood phenylalanine levels. This study concludes that sapropterin results in increased stability of blood phenylalanine levels in BH4-responsive PKU. Sapropterin therapy increases stability of blood phenylalanine […]
Deletions in OTC
Mol Genet Metab. 2009 Mar;96(3):97-105. Epub 2009 Jan 12. High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. Shchelochkov OA, Li FY, Geraghty MT, Gallagher RC, Van Hove JL, Lichter-Konecki U, Fernhoff PM, Copeland S, Reimschisel T, Cederbaum S, Lee B, Chinault AC, Wong LJ. http://www.ncbi.nlm.nih.gov/pubmed/19138872 This […]
UCD cross-sectional study in the US
This study performed by 8 US sites included 183 patients. The data was obtained by interviews, physical examinations, neuropsychological testing and laboratory analyses. OTC deficiency was the most frequent condition. 39% of all patients had intellectual and developmental disabilities. For more details on this very useful cross-sectional study, please refer to: Mol Genet Metab. 2008 […]
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