Neither maternal nor fetal mutation (E474Q) in the α-subunit of the trifunctional protein is frequent in pregnancies complicated by HELLP syndrome

Mütze, S.; Ahillen, Ines; Rudnik-Schoeneborn, Sabine; Eggermann, Thomas; Leeners, Brigitte; Neumaier-Wagner, P; Kuse, S; Rath, Werner; Zerres, Klaus

doi:10.1515/jpm.2007.012

Cited by 18 publications

(8 citation statements)

References 11 publications

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“…Retinopathy has been associated with deficiency of docosahexanoic acid (DHA) under a longchain fat-restricted diet (Gillingham et al 2005); however, low DHA levels have also been reported in VLCAD deficiency (VLCADD) that does not present with retinopathy. The occurrence of maternal hemolysis, liver dysfunction, and low platelets (HELLP syndrome) or acute fatty liver of pregnancy (AFLP) has been associated with an LCHAD-or TFP-deficient fetus; however, it also occurs in women not carrying an affected fetus (Mütze et al 2007). Recent evidence suggests a fetal-maternal interaction and approximately one in five women who develop AFLP or HELLP syndrome may carry an LCHAD-deficient fetus (Ibdah 2006).…”

Section: Lchad and Tfp Deficienciesmentioning

confidence: 99%

Mitochondrial fatty acid oxidation disorders: clinical presentation of long‐chain fatty acid oxidation defects before and after newborn screening

Spiekerkoetter

2010

J of Inher Metab Disea

147

151

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The different long-chain fatty acid oxidation defects present with similar heterogeneous clinical phenotypes of different severity. Organs mainly affected comprise the heart, liver, and skeletal muscles. All symptoms are reversible with sufficient energy supply. In some long-chain fatty acid oxidation defects, disease-specific symptoms occur. Only in disorders of the mitochondrial trifunctional protein (TFP) complex, including long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (LCHAD) deficiency, neuropathy and retinopathy develop that are progressive and irreversible despite current treatment measures. In most long-chain fatty acid oxidation defects, no clear genotype-phenotype correlation exists due to molecular heterogeneity. However, some isolated mutations have been identified to be associated with only mild phenotypes, e.g., the V243A mutation in very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. LCHAD deficiency is due to the prevalent homozygous 1528G>C mutation and presents with heterogeneous clinical phenotypes, suggesting the importance of other environmental and genetic factors. For some disorders, it was shown that residual enzyme activity measured in fibroblasts or lymphocytes correlated with severity of clinical phenotype. Implementation of newborn screening has significantly reduced morbidity and mortality of long-chain fatty acid oxidation defects. However, the severest forms of TFP deficiency are still highly associated with neonatal death. Newborn screening also identifies a great number of mildly affected patients who may never develop clinical symptoms throughout life. However, later-onset exercise-induced myopathic symptoms remain characteristic clinical features of long-chain fatty acid oxidation defects. Disease prevalence has increased with newborn screening.

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Section: Lchad and Tfp Deficienciesmentioning

confidence: 99%

Mitochondrial fatty acid oxidation disorders: clinical presentation of long‐chain fatty acid oxidation defects before and after newborn screening

Spiekerkoetter

2010

J of Inher Metab Disea

147

151

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“…7 Mutze y cols., publicaron la ausencia de la mutación fetal y materna en embarazos complicados con HELLP. 8 La mortalidad comunicada de los niños con deficiencia completa de PTM o LCHAD ha sido del 75-90%. 5 El tratamiento dietético temprano en estos niños reduce drásticamente la mortalidad.…”

Section: Discussionunclassified

Deficiencia de 3-hidroxiacil coA deshidrogenasa de cadena larga, asociación con HELLP y hallazgos en la espectroscopia por resonancia magnética

Deltetto¹

2012

Arch Argent Pediat

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RESUMENLa deficiencia de 3-hidroxiacil coA deshidrogenasa de cadena larga (LCHAD) es uno de los trastornos de la betaoxidación de ácidos grasos. La presentación clínica más frecuente incluye trastornos de conciencia, hipoglucemia y disfunción hepá-tica gatillados por ayuno prolongado o infecciones. Una vez desencadenada, la crisis metabólica presenta alta mortalidad. El síndrome HELLP y la hepatitis grasa aguda del embarazo (AFLP) son trastornos del tercer trimestre del embarazo. Se ha asociado estas enfermedades durante la gestación con defectos hereditarios de la betaoxidación en el feto. Comunicamos el caso clínico de un trastorno de beta oxidación (deficiencia de LCHAD) asociado a HELLP materno. Describimos como hallazgos en la resonancia magnética espectroscópica un pico de ácido láctico y lípidos significativo. La pesquisa de estos trastornos de la betaoxidación al nacimiento, ante el antecedente de HELLP materno, permite el diagnóstico de la enfermedad previo al desarrollo de los síntomas. Palabras clave: deficiencia de LCHAD, síndrome HELLP, pesquisa neonatal, resonancia magnética espectroscópica. SUMMARYLCHAD deficiency is a disorder of fatty acid beta oxidation. The most common clinical presentation includes disorders of consciousness, hypoglycemia and liver dysfunction triggered by prolonged fasting or infection. Once a metabolic crisis is triggered, there is a high mortality. HELLP syndrome and acute fatty liver failure of pregnancy (AFLP) are disorders of the third trimester of pregnancy. These diseases have been associated during pregnancy with hereditary defects of beta-oxidation in the fetus. We report a case of beta-oxidation disorder (LCHAD deficiency) associated with maternal HELLP. We described a peak of lipid and lactic on magnetic resonance spectroscopic Deficiencia de 3-hidroxiacil coA deshidrogenasa de cadena larga, asociación con HELLP y hallazgos en la espectroscopia por resonancia magnética

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“…Holub et al performed acylcarnitine profiles and LCHAD common mutation screening in 88 newborns from mothers who suffered HELLP syndrome in Austria, not detecting any fatty acid oxidation disorder in the offspring [4]. More recently Mutze et al investigated the frequency of the 1528G>C mutation in 103 mothers with HELLP syndrome, in 82 children of affected pregnancies, and in 21 fathers in families where fetal DNA was not available [6]. The mutation was not detected in the study population indicating that neither maternal nor fetal heterozygosity for the 1528G>C mutation is a relevant factor of HELLP syndrome.…”

Section: Discussionmentioning

confidence: 99%

Acute fatty liver of pregnancy and neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency

et al. 2008

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Here we report a 7-month-old girl with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency with hypoketotic hypoglycemia; the mother had a history of acute fatty liver in a previous pregnancy leading to fetal death at 34 weeks of gestation. The misense mutation 1528G > C was detected in both alleles in the proband and in one allele in both parents. We emphasize that screening for fatty acid oxidation disorders and specifically LCHAD deficiency should be performed in newborns from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe or recurrent HELLP syndrome.

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Neither maternal nor fetal mutation (E474Q) in the α-subunit of the trifunctional protein is frequent in pregnancies complicated by HELLP syndrome

Abstract: Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome.

Cited by 18 publications

References 11 publications

Mitochondrial fatty acid oxidation disorders: clinical presentation of long‐chain fatty acid oxidation defects before and after newborn screening

Mitochondrial fatty acid oxidation disorders: clinical presentation of long‐chain fatty acid oxidation defects before and after newborn screening

Deficiencia de 3-hidroxiacil coA deshidrogenasa de cadena larga, asociación con HELLP y hallazgos en la espectroscopia por resonancia magnética

Acute fatty liver of pregnancy and neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency

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