Definition
Organic acidemias are congenital metabolic disorders with OR transition, manifested by life-threatening severe metabolic acidosis attacks with high anion GAP in the first days of life, as a result of the accumulation of organic acids in body fluids due to various enzyme deficiencies.
Common Findings:
• Severe dehydration
• Ketoacidosis
• Hypoglycemia
• Hyperglycinemia
• Hyperammonemia (excluding MSUD)
• Neutropenia and thrombocytopenia.
• Severe vomiting (may mimic pyloric stenosis), central hypotonia, hypertonia in extremities, encephalopathy, convulsions are seen in the first 2-3 weeks after birth.
Maple Syrup Urine Disease (MSUD)
• It occurs as a result of the accumulation of branched chain amino acids and ketoacids due to the deficiency of branched chain α-ketoacid dehydrogenase enzyme complex activity required for the decarboxylation of the essential amino acids valine, leucine and isoleucine.
• It is autosomal recessive.
• Coenzyme is thiamine phosphate (vitamin B1).
• Isoleosin metabolites cause the smell of burnt sugar or bacon fenugreek in the urine.
• In the child who is normal at birth, in the 2-3 days occur Reluctance to feed, vomiting and dehydration . At the end of the first week, lethargy, convulsive seizures, characteristic odor in the urine and coma occur.
• Physical examination reveals hypertonicity and opistotonus and muscular rigidity. Hypotonia (trunk) and hypertonicity (extremity) are confused with neonatal tetanus due to attacks of muscular rigidity and repetitive limb movements such as boxing or cycling.
• There may be swelling of the anterior fontanelle with cerebral edema and it is confused with neonatal sepsis and meningitis.
Diagnosis:
• Diagnosis is made by detecting elevated plasma valine, leucine, isoleucine and alloisoleucine levels.
• In the urine, valine, leucine, isoleucine and their ketoacids are greatly increased. These ketoacids can be indicated by a yellow discoloration when a few drops of the 2,4-dinitrophenyl hydrazine (DNPH) reagent are dropped into the urine.
Treatment:
• The most effective treatment method is peritoneal dialysis. Mannitol and diuretics are given for cerebral edema.
• In the follow-up after acute treatment, a diet with restricted branched chain ammonacids should be given. Lifelong diet is essential.
• Some mild-to-moderate MSUD patients respond well to high-dose thiamine therapy.
• If isoleucine is excessively restricted in the diet, a picture similar to acrodermatitis enteropathica may develop.
Isovaleric Acidemia
• As a result of isovaleryl CoA dehydrogenase deficiency, the conversion of leucine to 3-methylcrotonic acid is impaired and isovaleryl CoA metabolites accumulate.
• Sweaty feet odor is its characteristic feature.
• acute attack; It is similar to diabetic ketoacidosis because of metabolic acidosis, ketosis, and hyperglycemia.
Diagnosis
Diagnosis is made by demonstrating the increase of isovaleric acid and isovaleric glycine in body fluids and urine.
Treatment
• Treatment consists of restoring hydration and removal of isovaleric acid and ammonia from the body. For this purpose, peritoneal dialysis can be performed.
• Isovaleric excretion is accelerated by increasing the formation of isovaleric glycine and isovaleryl carnitine, which have higher urinary clearance, by giving glycine and carnitine to the patients.
• A low protein diet is started.
Propionic Acidemia
• Propionyl CoA carboxylase is a biotin-dependent mitochondrial enzyme. In its deficiency, propionic acid and many metabolites of this acid accumulate in the blood and urine.
• The most important neurological sequela finding in children with propionic acidemia is metabolic stroke. In addition to pyramidal findings such as paraplegia, extrapyramidal findings such as dystonia, choreoathetosis and tremor due to basal ganglia (especially globus pallidus) damage are seen in these patients. Another important complication is cardiomyopathy and arrhythmias.
• Glycine accumulates in body fluids due to the inhibition of the glycine-degrading enzyme by the accumulated metabolites. This condition, which is also seen in patients with methylmalonic acidemia, is called ketotic hyperglycinemia.
Diagnosis
Propionic acid and methylcitric acid, which is a combination of propionic acid and oxaloacetate, are detected in the urine and blood. Accumulation of propionic acid in the blood can be confused with ethylene glycol poisoning.
Treatment
• Peritoneal dialysis and hemodialysis are used to remove ammonia and toxic metabolites in the treatment of acute attacks.
• Protein-poor diet, carnitine and biotin are used in the long-term follow-up of patients.
• Intestinal propionate production can be reduced with metronidazole.
Methylmalonic Acidemia
• It develops as a result of deficiency in methylmalonyl CoA mutase enzyme or defects in adenosylcobalamin formation.
• The cofactor is B12.
Diagnosis
• It is diagnosed with ketosis, acidosis, anemia, neutropenia, thrombocytopenia, hyperglycinemia and excessive accumulation of methylmalonic acid in body fluids.
• Cases who survived a severe attack in the neonatal period may relapse during infection periods or after high protein nutrition.
• One of the most important complications of methylmalonic acidemia is kidney involvement (Tubulointerstitial nephritis and CRF)
• This may be confused with ethylene glycol poisoning due to episodic clinical picture and biochemical abnormalities (propionate elevation in plasma).
• Metabolic stroke may develop as in propionic acidemia.
Treatment
• High dose of vitamin B12 is given. His diet is regulated and carnitine replacement is given.
• Intestinal propionate production can be reduced with metronidazole.
Beta-Ketothiolase Deficiency
Attacks can be confused with aspirin intoxication. The colorimetric acetoacetate test used for salicylate is positive.
Multiple Carboxylase Deficiency
• The cofactor of all carboxalases (pyruvate carboxylase, propionyl CoA carboxylase, 3-methylcrotinyl CoA carboxylase and acetyl CoA carboxylase) in the body is biotin.
• Free biotin enables cocarboxylases to become active. The enzyme holocarboxylase synthetase binds biotin to the apoproteins of carboxylase enzymes. The biotinidase enzyme also ensures that biotin is separated from these proteins and dietary proteins in the intestine.
• Deficiency of these enzymes or biotinidase results in dysfunction of all carboxylases and organic acidemia.
Biotinidase deficiency
• In the deficiency of biotinidase, the function of carboxylases, which play a role in gluconeogenesis, fatty acid synthesis and amino acid catabolism, which requires biotin, is impaired. It shows autosomal recessive inheritance.
• Symptoms appear between 1 week and 2 years after birth.
• Growth retardation, ataxia, myoclonic convulsions, hypotonia, skin findings (erythematous rash), alopecia, bilepharokeratoconjunctivitis, immunodeficiency (T cell), candidiasis, hearing loss, optic atrophy, ketoacidosis and organic aciduria, which can result in death, are observed in these patients. Lactic acid and ammonia levels rise.
• Response to free biotin (5-20 mg/day) is good in treatment.
Holocarboxylase synthetase deficiency
• OR passes. The findings are similar to biotinidase deficiency. It usually begins in the first week after birth. Even at birth, there are respiratory problems such as tachypnea and apnea.
• High dose biotin (10-80 mg/day) is used in the treatment.
Acquired biotin deficiency
• It is seen in those who take total parenteral nutrition therapy without biotin, those who use antiepileptics (phenytoin, carbamazepine and pyrimidone), those who have short bowel syndrome and those who eat raw eggs (avidin prevents biotin absorption).