Hepatic Carnitine Palmitoyltransferase I Deficiency Presenting as Maternal Illness in Pregnancy

Innes, A. Micheil; Seargeant, L.E.; Balachandra, K; Roe, Charles R.; Wanders, Ronald J. A.; Ruiter, J. P. N.; Casiro, Oscar G.; Grewar, David; Greenberg, Cheryl R.

doi:10.1203/00006450-200001000-00010

Cited by 138 publications

(68 citation statements)

References 14 publications

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“…The results clearly show that CPT-IA deficiency can easily be overlooked when using the classical biomarker, i.e., high concentrations of C0 in plasma, as the sole criterion for diagnosis, as previously reported (Bergman 1994;Bonnefont et al 2004;Innes et al 2000;Primassin and Spiekerkoetter 2010;de Sain-van der Velden et al 2013). Blood spot acylcarnitines, in particular the ratio of C0/ (C16:0-ac+C18:0-ac), seem to have high diagnostic value for CPT-IA deficiency (Fingerhut et al 2001;McHugh et al 2011;Primassin and Spiekerkoetter 2010;de Sain-van der Velden et al 2013;Sim et al 2001).…”

Section: Discussionsupporting

confidence: 50%

“…It became, however, increasingly clear that this diagnostic parameter is problematic and that the diagnosis could be easily overlooked since quite often the concentration of C0 in plasma was found to be normal (Bergman 1994;Bonnefont et al 2004;Innes et al 2000;Primassin and Spiekerkoetter 2010;de Sain-van der Velden et al 2013). It has been suggested that a high concentration of C0 in blood spot is more sensitive than its concentration in plasma (Primassin and Spiekerkoetter 2010;de Sain-van der Velden et al 2013;Sim et al 2001).…”

mentioning

confidence: 99%

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Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles

Heiner‐Fokkema

Vaz

Maatman³

et al. 2016

JIMD Reports

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Background: Carnitine palmitoyltransferase IA (CPT-IA) deficiency is an inherited disorder of the carnitine cycle (MIM #255120). Patients affected by this deficiency might be missed easily because of lack of specific and sensitive biochemical markers. In this study, sensitivity and specificity of plasma free carnitine (C0) and long-chain acylcarnitines (lc-ac: C16:0-, C16:1-, C18:0-, C18:1-and C18:2-ac) was evaluated, including the sum of lc-ac (∑lc-ac) and the molar ratios C0/(C16:0-ac+C18:0-ac) and C0/ ∑lc-ac.Methods: Nine plasma acylcarnitine profiles of 4 CPT-IA deficient patients were compared with profiles of 2,190 subjects suspected of or diagnosed with an inherited disorder of metabolism. Age-dependent reference values were calculated based on the patient population without a definite diagnosis of an inborn error of metabolism (n ¼ 1,600). Sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves were calculated based on samples of the whole patient population.Results: Concentrations of C0 in plasma were normal in all CPT-IA deficient patient samples. ROC analyses showed highest diagnostic values for C18:0-ac, C18:1-ac, and ∑lc-ac (AUC 1.000) and lowest for C0 (AUC 0.738). Combining two markers, i.e., a plasma C18:1-ac concentration <0.05 mmol/L and a molar ratio of C0/(C16:0-ac +C18:0-ac) >587, specificity to diagnose CPT-IA deficiency increased to 99.3% compared with either C18:1-ac (97.4%) or C0/(C16:0-ac+C18:0-ac) (96.9%) alone, all at a sensitivity of 100%.Conclusions: Combination of a low concentration of C18:1-ac with a high molar ratio of C0/(C16:0-ac+C18:0-ac) ratio in plasma has high diagnostic value for CPT-IA deficiency. Patients with a clinical suspicion of CPT-IA deficiency can be diagnosed with this test combination. Background

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Section: Discussionsupporting

confidence: 50%

mentioning

confidence: 99%

Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles

Heiner‐Fokkema

Vaz

Maatman³

et al. 2016

JIMD Reports

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“…carnitine palmitoyl transferase. 24 Presence of FAO defects in the fetus is estimated to increase by 18 fold the risk of AFLP and other pregnancy related disorders in the mother. 25 However, not all mothers with AFLP have these described mutations, 26,27 and not all mothers carrying fetus homozygous for these defects develop AFLP.…”

Section: Association Of Fetal Fatty Acid Oxidation Defects With Matermentioning

confidence: 99%

Pregnancy-Related Liver Disorders

Goel

Jamwal

Ramachandran

et al. 2014

Journal of Clinical and Experimental Hepatology

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Pregnancy-related liver disorders accounted for 8% of all maternal deaths at our center from 1999 to 2011. Of the three pregnancy-related liver disorders (acute fatty liver of pregnancy (AFLP), HELLP (Hemolysis, elevated liver enzymes, low platelets) syndrome and pre-eclamptic liver dysfunction, which can lead to adverse maternal and fetal outcome, AFLP is most typically under -diagnosed. Risk of maternal death can be minimised by timely recognition and early/aggressive multi-specialty management of these conditions. Urgent termination of pregnancy remains the cornerstone of therapy for some of these life threatening disorders, but recent advancements in our understanding help us in better overall management of these patients. This review focuses on various aspects of pregnancy-related liver disorders. ( J CLIN EXP HEPATOL 2014;4:151-162) A ny liver disorder can occur co-incidentally in pregnancy. Pregnancy can also occur in a patient with pre-existent chronic liver disorder/portal hypertension. In addition, liver dysfunction in pregnancy can also be secondary to pregnancy (i.e. pregnancy-related liver disorders). The 5 pregnancy-related liver disorders-acute fatty liver of pregnancy (AFLP), HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), pre-eclamptic liver dysfunction, intrahepatic cholestasis of pregnancy (ICP) and hyperemesis gravidarum-occur in different gestational time periods.

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“…Protrombin zamanı (PT) ve aktive parsiyel tromboplastin zamanında (APTT) uzama, ciddi hipoglisemi, artmış kreatinin düzeyi gibi bulguların akut yağlı karaciğerde görülme sıklılığı HELLP sendromundan daha fazladır. Akut yağlı karaciğer ile komplike olan kadınların çoğu HELLP sendromlu kadınlardan daha fazla olarak kalıtımsal yağ asitlerinin mitokondrial beta oksidasyon defekti, uzun zincirli 3 hidroksi açil koaenzim A dehidrojenaz eksikliği, kısa zincirli açil koenzim A dehidrojenaz eksikliği, karnitin palmitoiltransferaz 1 eksiklği gibi kazanılmış defektlere sahiptir 12,13,15,24,25 . Bu ayırıcı tanı için tipik bulgu değildir.…”

Section: Gebeliğin Akut Yağlı Karaciğeriunclassified

HELLP sendromu

ACAR¹,

ÇETİNDAĞ²,

ALKILIÇ³

et al. 2014

Arşiv Kaynak Tarama Dergisi

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1Ankara Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabulum Dalı, Ankara, Turkey ÖZET HELLP sendromu intravasküler hemoliz, karaciğer enzim yüksekliği ve trombosit düşüklüğü durumu olarak tanımlanmaktadır. %0,1ile %0,8 oranında bir insidansı mevcuttur. Genetik yatkınlık durumunda risk artmaktadır. Ayrıca preeklampsinin aksine multipartite riski artıran bir durumdur. Tanısı HELLP sendromu tanımında da yer alan değerlerdeki değişimlerle konulmaktadır. Özellikle trombosit sayısı sınıflamalarda da kullanılmaktadır. Ayırıcı tanıda akılda bulunması gereken durumlar şiddetli preeklampsi, gebeliğin akut yağlı karaciğeri, hemolitik üremik sendrom, trombotik trombositopenik purpura durumlar ile ayırıcı tanısı yapılması gerekmektedir. Maternal olarak disemine intravasküler koagülasyon (DIC), plasenta dekolmanı, akut renal yetmezlik, pulmoner ödem, subkapsüler karaciğer hematomu, retina dekolmanı gibi komplikasyonlar ile karşılaşabiliriz. Tedavide ise şu an için önerilen hastanın stabilizasyonu, kan basıncı kontrolü ve magnezyum sülfat infüzyonu başlanması önerilmektedir. Daha sonra ise fetal hafta, fetal distress ve maternal distress açısından değerlendirilerek bu risklerin olması durumunda doğum düşünülmelidir. Eğer risk faktörleri negatif ve fetus 24 ile 34 hafta arasında ise steroid dozu tamamlanıp devamında doğum planlanmalıdır. Sonuç olarak HELLP sendromunun kesin tedavisi doğumdur. Steroid tedavisi ve diğer tedavi seçenekleri ile ilgili geniş randomize çalışmalara ihtiyaç vardır. Anahtar kelimeler: HELLP sendromu, tanı, sınıflama, komplikasyon, tedavi ABSTRACT HELLP syndrome is characterized by hemolysis, elevated liver enzymes and thrombocytopenia. With anincidence of 0.1%-0.8% it is known to be effected by genetic predisposition. Unlike preeclempsia multiparity increases the risk of HELLP syndrome. Diagnosis is made by the classic clinical triad. Thrombocyte counts are especially important for classification of the disease. When making a

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Hepatic Carnitine Palmitoyltransferase I Deficiency Presenting as Maternal Illness in Pregnancy

Cited by 138 publications

References 14 publications

Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles

Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles

Pregnancy-Related Liver Disorders

HELLP sendromu

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