Deficiency of Phenylalanine Hydroxylase which converts Phenylalanine to Tyrosine. Build up of phenylalanine in the blood which disrupts brain development in an unknown manner.
Clinical Findings in Phenylketonuria
Newborn screening is now done.
If not detected early, will have mental retardation. If treatment is discontinued after age 6 will have more subtle mental problems later (disrupted executive planning, concentration and memory problems).
High levels of phenylalanine and its metabolites (phenylacetate and phenyllactate) in urine
Genetics of Phenylketonuria
Treatment of Phenylketonuria
Restrict phenylalanine in diet (all natural protein) to minimize flux through pathway. Treatment continues for life.
Provide high levels of tetrahydrobiotrin (BH4) cofactor to enhance function of residual enzyme.
Supplement with Tyrosine
Experimentation with replacement by bacterial enzyme.
Metabolic disorder which causes a build-up in non-amino organic acid intermediates on an amino acid metabolic pathway.
Pathology in Propionic Acidemia
Deficiency in propionyl-CoA carboxylase which causes a build up in propionic acid.
Propionyl CoA precursers include: - VOMIT: Valine, Odd-chain FAs, Methionine, Isoleucine, Threonine - Cholesterol, Thiamine, Uracil - Normal GI Flora
Clinical Findings in Propionic Acidemia
Normally identified in newborn screening.
Mental Retardation Recurrant metabolic decompensation End organ failure Short lifespan even with careful treatment.
Child presenting with vomiting. Acidotic with anion gap. High levels of organic acid in urine. High Plasma Ammonia
Treatment of Propionic Acidemia
VOMIT free dietary formulation and Antibiotics to reduce GI bacteria.
Supplement with Biotin cofactor
Carnitidine is given to help elimination of propionic acid.
Treat hyperammonemia and give bicarbonate to buffer pH.
BH4 deficiency / Malignant PKU
Deficiency of tetrahydrobioptrin cofactor essential for phenylalanine hydroxlase AND other enzymes.
Presents the same as PKU but must rule out BH4 deficiency because PKU treatment will not address additional enzymatic disorders.
Pathology of Ornathene Transcarboxylase Deficiency (OTC)
Urea cycle defect prevents metabolism of ammonia in the liver and leads to hyperammonemia.
Also blocks the production of citruline.
Clinical Findings in Ornathene Transcarboxylase Deficiency
Can cause seizures, cereberal edema, hyperventilation and alkalosis,
Atypical cases (some female carriers) can present during times of stress, such as pregnancy, or after high protein load.
Treatment of OTC
Restrict all protein intake, minimal levels of essential amino acids.
Supplement with Citrulline
Liver Transplant is recommended and is currently the only enzyme replacement for ornathene decarboxylate.
Dialysis to remove ammonia, ammnoia scavenging medications
Genetics of Ornathene Transcarboxylase Deficiency
Pathology of Galactosemia
Deficiency of any of the key enzymes required to catabolize galactose (from lactose)