Since most inherited metabolic disorders congenital Stoffwechselfhler) are rare, their diagnosis requires a high index of suspicion. Early diagnosis leading to early treatment and avoid acute and chronic complications, impairments in the development and even death. Clarification of symptoms and complaints are often non-specific and usually by something other than the inherited metabolic disorder (such as infection.) Gives; these similar causes must be investigated. History and physical examination disturbances already manifest in the newborn, are often more severe. Many of these disorders are typically associated with lethargy, Essschwierigkeiten, vomiting and seizures. The interference with a late manifestation relate more growth and development, but vomiting, seizures and weakness may also occur. Growth delays indicate more attention to a reduced anabolism or increased catabolism and can caused by a decreased availability of energy-providing substrates (z. B. glycogen storage diseases [GSE]) or an insufficient energy or protein consumption have (eg. As organic acidification or urea cycle disorders ). Development delays can have a chronic energy shortage in the brain reflect (eg disorders of oxidative phosphorylation.); a reduced supply of needed carbohydrates which do not constitute sources of energy for the brain (eg. B. absence of uridine 5′-Diphesphat-galactose in an untreated galactosemia) or a chronic amino acid deficiency in the brain (eg. B. Tyrosinmangel in phenylketonuria) , Neuromuscular symptoms such as convulsions, muscle weakness, hypotension, myoclonus, muscle pain, strokes or coma suggest an acute shortage of energy in the brain (eg. As hypoglycemic seizures in GSE type I, strokes in a disruption of mitochondrial oxidative phosphorylation) or (in the muscles z. B. muscle weakness in muscle forms of GSE) out. The neuromuscular symptoms may also to an accumulation of toxic substances in the brain point (z. B. hyperammonämisches coma in urea cycle defects) or tissue death (eg. As rhabdomyolysis and myoglobinuria in patients with a lack of long-chain Hydroxyacyldehydrogenasen or muscle forms of GSE). Congenital malformations of the brain may reflect (z. B. ATP reduced output at pyruvate dehydrogenase deficiency) or critical precursors (z. B. reduced cholesterol at 7-Dehydrocholestrol-reductase deficiency or Smith during fetal development a reduced availability of energy Lemli-Opitz syndrome). Autonomic symptoms can of hypoglycemia due to an increased consumption or decreased glucose production (eg. B. vomiting, diaphoresis, pallor, and tachycardia in glycogen storage diseases [GSE] or hereditary fructose intolerance) or metabolic acidosis (z. B. vomiting and Kussmaul respiration in organic acidosis) originate. Some diseases cause both so causes such. Example, in the propionic accumulation of acyl-CoA metabolic acidosis and inhibits gluconeogenesis, which in turn causes hypoglycemia. Non-Physiological jaundice after the neonatal period indicates an intrinsic liver disease, especially if it is accompanied by an increase of the liver enzymes, however, (e. B. untreated galactosemia, hereditary fructose intolerance, tyrosinemia type 1) can be also caused by congenital metabolic disorders. Unusual smell of body fluids may indicate the accumulation of specific components such. B. sweet smell grease in isovaleric, sweet smell of smoke in maple syrup syndrome, mouse smell phenylketonuria, cooked cabbage smell of tyrosinemia. Discoloration of urine during air exposure, in some disorders (eg. As dark brown in Alkaptonurie, violet brown in porphyria) occur. Organomegaly can give an indication that certain substrates which can not be removed, to (z. B. hepatomegaly with hepatic forms of GSE and many lysosomal storage disorders, cardiomegaly at GSE type II) deposited in the organ cells. Augenveränderungenmit cataract there in a Galaktokinasemangel or classic galactosemia, and ophthalmoplegia and retinal degeneration in defects in the oxidative Phosphorylierung.Tests When a congenital metabolic disease is suspected, the investigation begins first with a review of the results of neonatal screening examination and then arranges simple screening methods normally include: glucose electrolytes blood and peripheral blood smear liver ammonia levels serum amino acid levels urinalysis organic uric the glucose measurements reveal hyperglycemia and hypoglycemia, the measurements must be set in relation to meals (for example Nüchternhypoglykämie at GSE.). The electrolyte measurements can reveal a metabolic acidosis and the presence or absence of an anion; metabolic acidosis requires the simultaneous measurement of blood gases. A non-anion acidosis occurs congenital abnormalities that cause a tubular damage (eg. B. galactosemia, tyrosinemia type I). Acidosis with anion gap also occurs in congenital disorders with an accumulation of titratable acids such as methylmalonic and propionic acidemia, they may also by a lactic acidosis (eg. As in a Pyruvatdecarboxylasemangel or defects in mitochondrial oxidative phosphorylation) occur. If the anion gap is increased lactate and pyruvate should be determined. An increase in the lactate / pyruvate ratio can distinguish defects in oxidative phosphorylation from those of the pyruvate metabolism, wherein the lactate / pyruvate ratio remains normal. Clinical Calculator: anion blood count and peripheral smear may hemolysis by a lack of energy in the red blood cells or defects in white blood cells (eg, in some disorders of Pentosephosphatstoffwechsels or GSE type II.) And reveal a cytopenia caused by accumulation of metabolites (z. B. neutropenia in propionic acidemia by the accumulation of propionyl-CoA) is caused. Liver function can have a hepatocellular damage, dysfunction, or both discover (z. B. an untreated galactosemia, hereditary fructose intolerance or tyrosinemia type I). Elevated ammonia levels indicate urea cycle defects, organic Azidämien and disorders of fatty acid oxidation. A ketonuria (in some GSE and in some organic Azidämien) may be revealed by urine analysis; the absence of ketones with acidosis may indicate a defect in fatty acid oxidation. More specific tests can be useful if ? 1 simple screening tests described above can be a hereditary disorder of the metabolism suspect. Carbohydrate metabolites, mucopolysaccharides and amino, or organic acids can be measured directly by chromatography and mass spectrometry. Quantitative plasma amino acid testing should include a plasma acylcarnitine profile. Tests on organic acids in urine should include a urine acylglycine profile. Tests for the confirmation of the diagnosis can also include a biopsy (e.g., hepatic biopsy, in order to distinguish hepatic forms of GSE of other disorders with a hepatomegaly, muscle biopsies for detecting frayed muscle fibers in mitochondrial myopathies.); Enzyme studies (eg. As testing of blood and skin cells for the diagnosis of lysosomal storage diseases) and DNA tests to identify the causative gene mutation. DNA tests can be performed on almost all cells (except red blood cells and platelets), which tissue biopsies can be avoided. However, the sensitivity is suboptimal, because not all mutations are characterized. Provocation tests are used to detect symptoms, findings and measurable biochemical pathological values ??that can not be detected in normal status. The use of provocative tests has decreased since there was highly sensitive methods for the determination of metabolites, but sometimes they can also be employed. Examples include the Fast Test (z. B. provocation of hypoglycemia in the hepatic form of GSE), provocation test (z. B. fructose test, to trigger the symptoms of hereditary fructose intolerance, Glukagontest in hepatic forms of GSE [the absence of hyperglycemia indicates a disease toward]) and the physiological challenge (z. B. ergometry to illuminate a lactate acid production, and other disorders in the muscular shape of the GSE). Since the challenge tests are often associated with a risk, they must take place under well controlled conditions and with a careful plan in the event of side effects.


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