Acidemia isovaleric

Urine is preferred for these tests. The small volumes required make it practicable to spot the urine onto cotton fiber filter paper and allow it to dry out, for ease of shipment by mail. The limited experience in applying MS/ MS for these analytes suggests that the levels of pathognomonic metabolites should significantly exceed control values for purines and pyrimidines regardless of the patient s clinical state (Table E.4). This is true also of acyl-glycines for certain disorders such as propionic acidemia, isovaleric acidemia and MCAD deficiency (Table E.3), although it appears that most other... 

Reaction 3 is analogous to the dehydrogenation of fatty acyl-CoA thioesters (see Figure 22—3). In isovaleric acidemia, ingestion of protein-rich foods elevates isovalerate, the deacylation product of isovaleryl-CoA. Figures 30-20, 30-21, and 30-22 illustrate the subsequent reactions unique to each amino acid skeleton. 

Mutation of the dihydrolipoate reductase component impairs decarboxylation of branched-chain a-keto acids, of pyruvate, and of a-ketoglutarate. In intermittent branched-chain ketonuria, the a-keto acid decarboxylase retains some activity, and symptoms occur later in life. The impaired enzyme in isovaleric acidemia is isovaleryl-CoA dehydrogenase (reaction 3, Figure 30-19). Vomiting, acidosis, and coma follow ingestion of excess protein. Accumulated... 

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Low protein diet to restrict intake of leucine (precursor to isovaleric acidemia)... 

Intravenous L-camitine and acetyl-L-camitine in medium-chain acyl-coenzyme A dehydrogenase deficiency and isovaleric acidemia. 

Tanaka (1990) Isovaleric acidemia personal history, clinical survey, and study of the molecular basis. Progr Clin Biol Res 321 273-290... 

Fig. 3.2.5 Profiles of acylcarnitines as their butyl esters in plasma (precursor of m/z 85 scan) of a normal control (a) and patients with various organic acidemias. Propionylcarnitine (C> m/z 274 peak 3) is the primary marker for both propionic acidemia (b) and methylmalonic acidemias (c). Note that an elevation of methylmalonylcarnitine (C4-UC m/z 374) is not typically found in patients with methylmalonic acidemias. In the three cases of ethylmalonic encephalopathy (d) analyzed in our laboratory, elevations of ,- (m/z 288 peak 4) and C5-acylcarnitine (m/z 302 peak 5) species were noted. Isolated C5-acylcarnitine elevations are encountered in patients with isovaleric acidemia (e), where it represents isovalerylcarnitine. Cs-Acylcarnitine is also elevated in patients with short/branched chain acyl-CoA dehydrogenase deficiency, where it represents 2-methylbutyrylcarnitine (see Fig. 3.2.4), and in patients treated with antibiotics that contain pivalic acid, where it represents pivaloylcarnitine [20, 59, 60]. Patients with /3-ketothio-lase deficiency (f) present with elevations of tiglylcarnitine (C5 i m/z 300 peak 6) and C5-OH acylcarnitine (m/z 318 peak 7). In most cases of 3-methylcrotonyl-CoA carboxylase deficiency (g) Cs-OH acylcarnitine is the only abnormal acylcarnitine species present. The differential diagnosis of C5-OH acylcarnitine elevations includes eight different conditions (Table 3.2.1). Also note that C5-OH acylcarnitine represents 3-hydroxy isovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase deficiency (g), and 2-methyl 3-hydroxy butyrylcarnitine in / -ketothiolase deficiency...

Roe CR, Millington DS, Maltby DA, Kahler SG, Bohan TP (1984) L-carnitine therapy in isovaleric acidemia J Clin Invest 74 2290-2295... 

Ensenauer R, Vockley J, Willard JM, et al (2004) A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet 75 1136-1142... 

Leucine Isovaleric acidemia Neonatal vomiting, acidosis, lethargy, and coma survivors mentally retarded Isovaleryl-CoA dehydrogenase... 

Figure 20.20 Pathways of branched-chain amino acid metabolism. A, B, C, D, E, and F indicate defects in valinemia, maple syrup urine disease, isovaleric acidemia, /3-hydroxyisovaleric aciduria, a-methyl-j3-hydroxybutyric aciduria, and methylmalonic aciduria, respectively.

Isovaleric acidemia. This is believed to be a defect in the step from isovaleryl Co A to beta-methyl cro-tonyl Co A, in the metabolism of leucine. Rather than a maple syrup odor, there is an odor of sweaty feet . The patient has various neurologic disturbances and mental retardation. Isovaleric acid is elevated in the plasma. It is treated by restricting dietary intake of leucine. 

Therapeutic glycine. Isovaleric acidemia is an inherited disorder of leucine metabolism caused by a deficiency of isovaleryl CoA dehydrogenase. Many infants having this disease die in the first month of life. The administration of large amounts of glycine sometimes leads to marked clinical improvement. Propose a mechanism for the therapeutic action of glycine. 

Isovaleric acidemia (an autosomal recessive disorder of leucine metabolism causing episodes of acidosis during catabolic stress) and carnitine deficiency have been associated with a lowered threshold for bupivacaine-induced dysrhythmias (SEDA-22,142). 

Isovaleric acidemia (IVA) is a disorder of leucine catabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. Since the initial report 40 years ago, IVA has been the main focus of the work of Dr. Kay Tanaka, one of the pioneers and arguably most productive contributors to our current... 

Figure 55-14 Plasma profiles of plasma acylcarnitine butyl-ester derivatives. A, Normal control. B, Propionic acidemia. C, Short-chain acyl-CoA dehydrogenase deficiency. D, Isovaleric acidemia. E, Medium-chain acyl-CoA dehydrogenase deficiency. F, Very long-chain acyl-CoA dehydrogenase deficiency. G, Long-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency.The symbol marks internal standards [ Hjj-acetylcarnitine (m/z 263) [ HaJ-propionylcarnitine (m/z 277) fH ]-butyrylcarnitlne (m/z 295) pHal-octanoylcarnitine (m/z 347) [ Haj-dodecanoylcarnltine (m/z 403) [ Haj-palmitoy I carnitine (m/z 459).

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