Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency
Humans; Male; Prognosis; Mutation; Longitudinal Studies; Phenotype; Fibroblasts/metabolism; Lipid Metabolism; Multienzyme Complexes/deficiency; Mitochondria/pathology; Acyl-CoA Dehydrogenase; Cardiomyopathies/diagnosis/genetics; Carnitine/analogs & derivatives/metabolism; Exons; Fatty Acids/metabolism; Homozygote; Inborn Errors/diagnosis/genetics; Long-Chain/deficiency; Polyneuropathies/diagnosis/genetics; Rhabdomyolysis/diagnosis/genetics
General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency resulting from the common Glu510Gln mutation usually gives rise to a moderately severe phenotype with multiorgan involvement with high morbidity and mortality. However, isolated LCHAD deficiency can also be consistent with long-term survival in patients identified and treated from an early age. We present biochemical, clinical and mutation data in 9 patients spanning the full spectrum of disease. Fibroblast acylcarnitine profiling shows good correlation with clinical phenotype using the ratio C18(OH)/(C14(OH)+C12(OH)). This ratio shows a gradation of values, from high in four patients with severe neonatal disease (2.5+/-0.8), to low in two neuromyopathic patients (0.35, 0.2). Fibroblast fatty acid oxidation flux assays also show correlation with the patient phenotype, when expressed either as percentage residual activity with palmitate or as a ratio of percentage activity of myristate/oleate (M/O ratio). Fibroblasts from four patients with severe neonatal disease gave an M/O ratio of 4.0+/-0.6 compared to 1.97 and 1.62 in two neuromyopathic patients. Specific enzyme assay of LCHAD and long-chain 3-ketothiolase activity in patient cells shows lack of correlation with phenotype. These results show that measurements in intact cells, which allow all determinative and modifying cellular factors to be present, better reflect patient phenotype. Mutation analysis reveals a number of alpha- and beta-subunit mutations. Peripheral sensorimotor polyneuropathy, often as the initial major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed.
2005
Olpin SE; Clark S; Andresen BS; Bischoff C; Olsen RK; Gregersen N; Chakrapani A; Downing M; Manning NJ; Sharrard M; Bonham JR; Muntoni F; Turnbull DN; Pourfarzam M
Journal Of Inherited Metabolic Disease
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1007/s10545-005-0533-8" target="_blank" rel="noreferrer">10.1007/s10545-005-0533-8</a>
The goldilocks paradigm of starvation and refeeding
Humans; Blood Glucose/metabolism; Energy Metabolism/physiology; Fatty Acids/metabolism; Proteins/metabolism; Malnutrition/metabolism/therapy; Nutritional Support/contraindications/ethics; Starvation/metabolism/therapy
2006
Palesty JA; Dudrick SJ
Nutrition In Clinical Practice : Official Publication Of The American Society For Parenteral And Enteral Nutrition
2006
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1177/0115426506021002147" target="_blank" rel="noreferrer">10.1177/0115426506021002147</a>
Recurrent metabolic decompensation in profound carnitine palmitoyltransferase II deficiency
Child; Humans; Male; Preschool; Q3 Literature Search; Recurrence; Fatty Acids/metabolism; Lymphocytes/metabolism; Carnitine O-Palmitoyltransferase/deficiency/metabolism; Creatine Kinase/metabolism; Energy Intake; Liver/enzymology; Transaminases/metabolism
A 3-year-old boy had recurrent episodes of lethargy, encephalopathy, and hepatomegaly accompanied by hypoglycemia, elevated liver aminotransferase and creatine kinase values, and nonketotic dicarboxylic aciduria; the serum carnitine level was moderately reduced. Carnitine palmitoyltransferase II activity was decreased in lymphocytes and fibroblasts. Therapy with L-carnitine and a diet low in long-chain triglycerides did not prevent recurrent episodes.
1993
Elpeleg ON; Joseph A; Branski D; Christensen E; Holme E; Demaugre F; Saudubray JM; Gutman A
The Journal Of Pediatrics
1993
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/s0022-3476(09)90019-1" target="_blank" rel="noreferrer">10.1016/s0022-3476(09)90019-1</a>