Lysine-Glycine Metabolism Disorders
Glutaric Acidemia Type 1:
• Glutaryl CoA is a joint product of lysine and tryptophan metabolism. Glutaric acidemia type I has glutaryl CoA dehydrogenase deficiency. This disease should not be confused with glutaric acidemia type II, an electron transport disorder.
• Patients may be asymptomatic for the first 2 years. In this asymptomatic period, there are some insidious neurological findings (irritability, hypotonia) and macrocephaly.
• In some patients, acute encephalopathic crises (dystonia, choreoathetosis, loss of head control, opistotonus) suddenly begin following infection. Even after the attack, dystonia and extrapyramidal findings remain. Mental development is usually normal.
• In another form, neurological findings progress slowly and metabolic crises (ketoacidosis, hyperammonemia, hypoglycemia) also develop in these patients.
• MR imaging shows degeneration of the putamen and caudate nucleus, and cortical atrophy (frontotemporal atrophy and hydrocephalus).
• Often confused with child abuse.
• Tryptophan and lysine restricted diet, riboflavin (B2) and carnitine are used in the treatment.
Lysinuric Protein Intolerance
• It is an autosomal recessive disorder of the transport system that ensures the absorption of lysine, ornithine and arginine in the intestine and kidney.
• Hyperammonemia attacks begin, especially after supplemental food and protein feeding.
• Mental development is generally normal.
• Osteoporosis, brittle hair and short stature are other findings. Some complications may develop in the course of lysinuric protein intolerance. Interstitial pneumonia is a hemophagocytic lymphohistiocytosis/macrophage activation syndrome with renal failure starting with fibrosis and alveolar proteinosis, hematuria and proteinuria.
• Protein-restricted diet and citrulline supplementation prevent hyperammonemia, but not organ complications.
Non-Ketotic Hyperglycinemia
• It develops as a result of the deficiency of mitochondrial glycine-destructive enzyme that converts glycine to CO2 and NH3.
• The most common form is neonatal non-ketotic hyperglycinemia.
• It progresses with non-sucking, lethargy, hypotonia, myoclonic seizures and hiccups between 6 hours and 8 days after birth.
• Glycine is high in blood and CSF. CSF/plasma glycine ratio increased (>0.08). In living children, psychomotor retardation and epilepsy remain.
• There is no effective treatment. Glycine restricted diet, sodium benzoate treatment does not change the neurological picture.
Histidin And Aspartate Metabolism Disorders
Histidine decarboxylase deficiency
Deficiency of the enzyme histidine decarboxylase, which produces histamine from histidine, results in familial Tourette's syndrome.
Canavan's Disease
• It is a leukodystrophy disease that develops as a result of the deficiency of the enzyme aspartoacylase, which removes the N acetyl group from N-acetyl aspartate.
• It starts with progressive macrocephaly, hypotonia, and delayed development between 3-6 months, and results in death towards the age of 1 as a result of spasticity, optic atrophy, convulsions and swallowing problems.
• Detection of N acetyl aspartate in the urine is diagnostic.