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Abstract: Background: There is increasing evidence that long‐term complications in organic acidemias are caused by impaired mitochondrial metabolism. Currently, there is no specific biomarker to monitor mitochondrial dysfunction in organic acidemias. Serum fibroblast growth factor 21 (FGF‐21) is a biomarker for mitochondrial disease and could be a candidate to monitor mitochondrial function in the deleterious course of disease. Methods: Data of 17 patients with classical organic acidemias (11 propionic acidemia (PA), four methylmalonic acidemia (MMA) and two isovaleric acidemia (IVA) patients) were included. The clinical course was evaluated; metabolic decompensations and long‐term complications were correlated with plasma FGF‐21 levels. Cardiomyopathy, prolonged QT interval, renal failure, and optic neuropathy were defined as long‐term complications. Results: Patients ages ranged from 16 months up to 32 years. Serious long‐term complications occurred in eight patients (five PA and three MMA patients). In MMA and PA patients plasma FGF‐21 levels during stable metabolic periods were significantly higher in patients with long‐term complications (Mdn = 2556.0 pg/ml) compared to patients without (Mdn = 287.0 pg/ml). A median plasma FGF‐21 level above 1500 pg/ml during a stable metabolic period, measured before the occurrence of long‐term complications, had a positive predictive value of 0.83 and a negative predictive value of 1.00 on long‐term complications in MMA and PA patients. Conclusion: This study demonstrates the potential role of FGF‐21 as a biomarker for long‐term complications in classical organic acidemias, attributed to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Key Clinical Message Severe recessive mitochondrial myopathy caused by FBXL4 gene mutations may present prenatally with polyhydramnios and cerebellar hypoplasia. Characteristic dysmorphic features are: high and arched eyebrows, triangular face, a slight upslant of palpebral fissures, and a prominent pointed chin. Metabolic investigations invariably show increased serum lactate and pyruvate levels. [ABSTRACT FROM AUTHOR]

The GLUT-1 deficiency is a metabolic disorder caused by a defect in glucose transport across the blood–brain barrier as a result of a defect in the glucose-transport protein. Patients present with epileptic seizures, delayed development, ataxia and hypotonia, and in many cases acquired microcephaly. In most patients, treatment with a ketogenic diet proved to be successful in controlling the epilepsy. We report a 9-year-old boy with retardation and ataxia, but without epilepsy, caused by GLUT-1 deficiency, proven biochemically and by DNA analysis. Treatment with a medium-chain triglyceride ketogenic diet had a beneficial effect. [ABSTRACT FROM AUTHOR]

The fatty acid composition was determined of liver, skeletal muscle and heart obtained post mortem from patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD), multiple acyl-CoA dehydrogenase deficiency (MADD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Increased amounts of 4-decenoic acid 10:1( n−6), 5-dodecenoic acid 12:1( n−7), 5-tetradecenoic acid 14:1( n−9), 5,8-tetradecadienoic acid 14:2( n−6) and 7,10-hexadecadienoic acid 16:2( n−6)—intermediates of unsaturated fatty acid oxidation—were found. Fractionation into different lipid classes showed that these fatty acids were exclusively present in the triglyceride fraction. They could not be detected in the free fatty acid fraction or in the phospholipid fraction. Our results suggest that intermediates of unsaturated fatty acid oxidation that accumulate as a consequence of MCADD, MADD and VLCADD are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation is characteristic for each disease, which makes fatty acid analysis of total lipid of post-mortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who died unexpected, for example with sudden infant death syndrome. [ABSTRACT FROM AUTHOR]

Evidence for the isomerization of the [M + NH4]+ adducts of nitrobenzene and triphenylnitrocyclohexenes to the isonitroso derivatives in the first field free region has been obtained. The isomerized adducts undergo successive loss of ṄO and ȮH or NH3 to give ions corresponding to the substitution products. Mass analysed ion kinetic energy and collisionally activated dissociation/mass analysed ion kinetic energy data reveal that the adduct decomposes by similar pathways in the second field free region. In the ion source an addition elimination reaction and nucleophilic substitution contribute to the formation of the substituted product ion. [ABSTRACT FROM AUTHOR]

For compounds C6H5X (XCl, Br, I) under chemical ionization conditions, methylamine causes ipso substitution of X by [NH2CH3]+ and by [NH2]+˙. C6H5F is less reactive; it gives some [C6H5NH2]+˙. Nitrobenzene gives an adduct ion [M+CH3NH3]+, a reduction product ion [C6H5NO2]+˙, and an ion at m/ z93, probably a substitution product [C6H5NH2]+˙, but no [C6H5NH2CH3]+. It is also shown that the ion m/ z94, formed from nitrobenzene with ammonia as reagent gas, is a substitution product rather than a reduction product ion. Carbonyl compounds C6H5. CO. X give adduct ions and some substitution, mainly [C6H5NH2]+˙. [ABSTRACT FROM AUTHOR]