Correction of secondary carnitine depletion Like many other organic acidemias,<unk>  causes carnitine depletion. Whole-blood carnitine can be raised by oral supplementation. However, this does not significantly change blood concentrations of glutarylcarnitine or esterified carnitine, suggesting that oral supplementation is suboptimal in raising tissue levels of carnitine. Clinical nutrition researchers have likewise concluded that oral carnitine raises plasma levels but does not affect those in muscles, where most of it is stored and used. In contrast, regular intravenous infusions of carnitine cause distinct clinical improvements: "decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake." Choline increases carnitine uptake and retention. Choline supplements are inexpensive, are safe (probably even in children requiring anticholinergics) and can increase exercise tolerance, truncal tone and general well-being, providing evidence of the suboptimal efficiency of carnitine supplementation alone. Selective precursor restriction Dietary control may help limit progression of the neurological damage. Lysine Lysine restriction, as well as carnitine supplementation, are considered the best predictors of a good prognosis for<unk> . This excludes, however, patients who already suffered an encephalopathic crisis, for whom the prognosis is more related to the treatment of their acquired disorder (striatal necrosis, frontotemporal atrophy). Protein restriction Vegetarian diets and, for younger children, breastfeeding are common ways to limit protein intake without endangering tryptophan transport to the brain. Tryptophan Formulas such as XLys, XTrp Analog, XLys, XTrp Maxamaid, XLys, XTrp Maxamum or Glutarex<unk>  are designed to provide amino acids other than lysine and tryptophan, to help prevent protein malnutrition. The entry of tryptophan into the brain is crucial in the proper synthesis of the neurotransmitter serotonin in the brain. One way to acutely cause depression, bulimia or anxiety in humans, in order to assess an individual's vulnerability to those disorders, is to supplement with a formula with all or most amino acids except tryptophan. Acute tryptophan depletion is a diagnostic procedure, not a treatment for<unk> . The protein synthesis elicited by the amino acids leads circulating amino acids, including tryptophan, to be incorporated into proteins. Tryptophan is thus lowered in the brain as a result of the protein synthesis enhancement, causing circulating tryptophan to drop more than other amino acids. A relative excess of other large neutral amino acids may also compete with tryptophan for transport across the blood–brain barrier through the large neutral amino acid transporter<unk> . The consequence is acute tryptophan depletion in the brain and a consequent decrease in serotonin synthesis. 5-Hydroxytryptophan, a precursor of serotonin that is not metabolized to glutaryl-CoA,<unk>  acid and secondary metabolites, could be used as an adjunct to selective tryptophan restriction, although it has risks. However, the evidence in favour of selective tryptophan restriction remains insufficient and the consensus is evolving towards the restriction of lysine only. In the Amish community, where<unk>  is overrepresented, patients with<unk>  typically do not receive tryptophan-free formulas, either as the sole source of amino acids or as a supplement to protein restriction. Enhancement of precursor anabolic pathways Lysine and hydroxylysine anabolic pathway enhancement A possible way to prevent the build-up of metabolites is to limit lysine and hydroxylysine degradation, as lysine is one of the most abundant amino acids and tryptophan is one of the least abundant amino acids. Interaction of GCDH deficiency with vitamin C levels Humans lack the enzyme L-gulonolactone oxidase, which is necessary for the synthesis of ascorbic acid (vitamin C), leaving them dependent on dietary sources of this vitamin. Vitamin C is a necessary cofactor for the utilization of lysine in collagen synthesis. Collagen, the most abundant protein in the human body, requires great amounts of lysine, the most abundant amino acid in proteins. Ascorbic acid, the main hydroxyl radical quencher, works as the cofactor providing the hydroxyl radical required for collagen cross-linking; lysine thus becomes hydroxylysine.<unk>  worsens during stresses and catabolic episodes, such as fasts and infections. Endogenous catabolism of proteins could be an important route for<unk>  acid production. It follows that collagen breakdown (and protein breakdown in general) should be prevented by all possible means. Ascorbic acid is used to prevent multiple organ failure and to lessen mortality and morbidity in intensive care units. It thus appears reasonable to add sufficient doses of ascorbic acid to the treatment protocol during stresses and other challenges to growth in order to stimulate collagen synthesis and thus prevent lysine breakdown. Tryptophan anabolic pathway enhancement The conversion of tryptophan to serotonin and other metabolites depends on vitamin B6. If tryptophan catabolism has any impact on brain<unk>  acid and other catabolite levels, vitamin B6 levels should be routinely assayed and normalized in the course of the treatment of<unk> . Management of intercurrent illnesses Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.
Glutaric aciduria type 1
Aspartylglucosaminuria
Hawkinsinuria
Alkaptonuria
Homocystinuria
2-Hydroxyglutaric aciduria
Essential fructosuria
Phenylketonuria