Organic aciduria

Organic acidurias are a group of several dozen diseases with a common characteristic: the excretion of carboxylic acids in the urine. Organic acids accumulate in the body when the metabolism is disturbed, especially amino acids, then fatty acids and carbohydrates, rarely other substances.

Heredity:

Pathogenesis:

  • disorder of the cytosolic, mitochondrial or peroxisomal metabolic pathway (enzyme deficiency, cofactor deficiency)
  • substrate accumulation prior to failure

Symptoms:

Forms:

  1. Acute neonatal
    • severe disorder of intermediary metabolism
    • manifests itself in the first days or weeks of life
  2. Intermittent
    • partial deficiency of an enzyme that is sufficient for intermediate metabolism under normal conditions
    • the provoking stimulus is increased catabolism (e.g. surgery), increased protein intake, prolonged starvation
    • they are manifested by attacks of acute encephalopathy, acidosis, hypoglycemia
  3. Chronically ongoing
    • less common, progressive, difficult to influence
    • CNS disorders

The organic acidurias investigated as part of the nationwide newborn screening in the Czech Republic include:

Methylmalonic acidemia

  • It belongs to the group of organic acidurias
  • It is a disorder of the Methylmalonyl-Coa mutase enzyme
  • inheritance is AR
  • its non-hereditary form is caused by an excess of vitamin B12, which is a cofactor of the said enzyme

Clinical picture

  • a short symptom-free period after birth
  • then vomiting
  • lethargy
  • progressive impairment of consciousness
  • brain edema
  • liver and kidney failure
  • children die under the guise of sepsis, bleeding, or shock
  • in the acute stage - ketoacidosis and laboratory signs of liver and kidney failure
  • glycine, valine, methionine and methylmalonic acid are higher in blood and urine

Diagnosis

  • examination of organic AMK in urine and blood
  • the exact type of defect will be determined by enzymatic examination of cultured fibroblasts

Therapy

  • if suspected, protein intake should be stopped and muscle catabolism-glucose infusion must be avoided
  • with early treatment the prognosis can be good
  • in critically ill patients, we must use elimination methods for treatment: hemodialysis, hemodiafiltration, peritoneal dialysis and exchange transfusion (descending efficiency).
  • a lifelong diet with a restriction of the amino acids isoleucine, valine, methionine and threonine with the addition of essential AMK and carnitine in food supplements is necessary.[1]

References

  • HYÁNEK, Josef, et al. Dědičné metabolické poruchy. 1.. edition. Praha : Avicenum, 1990. pp. 342. ISBN 80-201-0064-4.
  1. ↑ BENEŠ, Jiří. Studijní materiály [online]. ©2007. [cit. 2010-04]. <http://www.jirben.wz.cz/>. HRODEK, Otto – VAVŘINEC, Jan, et al. Pediatrie. 1. edition. Praha : Galén, 2002. ISBN 80-7262-178-5.
Hereditary Metabolic Disorders (HMDs)
In general DMP of complex molecules • DMP of small molecules • Newborn screening • Screening for hereditary diseases • Examination methods for DMP
DMP amino acids Alkaptonuria
Organic aciduria –
DMP of the urea cycle Alkaptonuria • Ornithine transcarbamylase deficiency • Prolidase deficiency • Phenylketonuria • Glutaric aciduria • Hyperphenylalaninemia • Hyperornithineemia • Isovaleric aciduria • Leucinosis • Nonketotic hyperglycinemia • Cystinosis • Tyrosinemia
DMP of propionate, biotin

and cobalamin

Biotinidase deficiency • Methylmalonic acidemia • Propionic acidemia
DMP of purines and pyrimidines Hepatic porphyria • Cutaneous porphyria • Mitochondrial neurogastrointestinal encephalomyopathy
DMP sugars Glycogenoses • Fructoaldolase deficiency • Fructose-1,6-bisphofatase deficiency • Essential fructosuria • Galactokinase deficiency • Galactose-1-phosphate uridyltransferase deficiency
Mitochondrial DMP Phosphoenolcarboxykinase deficiency • LCHAD deficiency • MCAD deficiency • Pyruvate dehydrogenase deficiency • Pyruvate carboxylase deficiency • SCAD deficiency • Chronic progressive external ophthalmoplegia • Leber's hereditary optic neuropathy • Leigh syndrome • Maternal diabetes and deafness • Kearns -Sayre syndrome • VLCAD deficiency
DMP of peroxisomes Neonatal adenodystrophy • Refsum disease • Rhizomelic chondrodystrophia punctata • X-linked adrenoleukodystrophy • Zellweger syndrome
DMP of lysosomes Fabry disease • Gaucher disease • Krabbe disease • Danon disease • Mucolipidosis II • Metachromatic leukodystrophy • Mucopolysaccharidosis III • Niemann-Pick disease • Cystinosis • Tay-Sachs disease
Portal: Pathobiochemistry