Phenylketonuria

Genome research is emerging as a new and important tool in biology used to obtain information on gene sequences, genomic interaction, and how genes work in concert to produce the final syndrome or phenotype. Defect in phenylalanine hydroxylase (PAH) gene result in Phenylketonuria (PKU). Molecular studies using the brain of the mouse model for PKU (PAHenu2) showed altered expression of several genes including upregulation of orexin A and a low activity of branched chain aminotransferase. These studies suggest that a single gene (PAH) defect is associated with altered expression, transcription and translation of other genes. It is the combination of the primary gene defect, the altered expression of other genes, and the new metabolic environment that is created, which lead to the phenotype

Methylmalonic Acidemia: Can Treatment be Improved?

Methylmalonic acidemia (MMA) is a severe metabolic disorder, particularly with complete deficiency of methylmalonyl-CoA mutase. Dietary restriction has led to overt signs of deficiencies including skin rashes, hair loss, and poor growth. More liberal intake of the restricted amino acids has resulted in better growth and less frequent episodes of illness

Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders

Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we propose may be responsible for ASDs and developmental delay

Treatment of Inborn Errors of Urea Synthesis — Activation of Alternative Pathways of Waste Nitrogen Synthesis and Excretion

Abstract Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation. The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium (±S.E.) was 36±2 μmol per liter, and that of benzoate was 1.5±1.0 mg per deciliter. Alternative pathways accounted for between 28 and 59 per cent of the total effective excretion of waste nitrogen. Nineteen infants had normal height, weight, and head circumference, and 13 had normal intellectual development. Activation of alternative pathways of waste nitrogen excretion can prolong survival and improve clinical outcome in children with inborn errors of urea synthesis. (N Engl J Med. 1982; 306:1387–92.