CASE REPORT

A Case of Severe Preeclampsia Leading to theDiagnosis of De Novo Abnormal Fatty AcidMetabolism and ACE Gene DeletionJesus I. Iruretagoyena, MD, Dinesh Shah, MDMaternal Fetal Medicine Division, Department of Obstetrics and Gynecology, Meriter Hospital, University of Wisconsin, Madison WI

Abstract

Background: Enzymes involved in the metabolism of free fatty acidsare essential for the proper use of caloric intake. Abnormalenzymes unable to degrade fatty acids will result in anaccumulation of fatty acids in organs like the liver, impairing itsfunction.

Case: A 28-year-old primigravid woman underwent induction oflabour because of severe preeclampsia. She was subsequentlyfound to be a carrier for mutations in several fatty acid enzymes aswell as the angiotensin converting enzyme.

Conclusion: During pregnancy, the increased need for fatty aciddegradation will expose women who are carriers of mutations inthese enzymes. The clinical manifestations in such women includeacute fatty liver of pregnancy that may mimic severepreeclampsia. Strict metabolic control to avoid excess fatty aciddegradation may allow for better pregnancy outcomes andnewborn assessment.

Résumé

Contexte : Les enzymes mis en cause dans le métabolisme desacides gras libres sont essentiels pour une bonne utilisation del’apport calorique. La présence d’enzymes anormaux incapablesde dégrader les acides gras entraînera une accumulation d’acidesgras dans des organes comme le foie, nuisant ainsi à sonfonctionnement.

Cas : Une primigravide de 28 ans a subi un déclenchement du travailen raison d’une grave prééclampsie. Nous avons subséquemmentconstaté qu’elle était porteuse de mutations affectant plusieursenzymes d’acide gras, ainsi que l’enzyme de conversion del’angiotensine.

Conclusion : Pendant la grossesse, la nécessité accrue de dégraderles acides gras fera en sorte de mettre en évidence les femmesqui s’avèrent être porteuses de mutations affectant les enzymes

mis en cause. Parmi les manifestations cliniques chez ces femmes,on trouve le foie gras aigu de la grossesse, lequel peu imiter laprééclampsie grave. Une maîtrise métabolique stricte visant àéviter la dégradation excessive des acides gras pourrait permettrel’obtention de meilleures issues de grossesse et la tenue d’unemeilleure évaluation néonatale.

J Obstet Gynaecol Can 2010;32(7):695–697

INTRODUCTION

Preeclampsia is commonly diagnosed by the presence of

hypertension and proteinuria during pregnancy. Severe

preeclampsia is considered when secondary organ manifes-

tations are seen.1 Liver involvement is one the most serious

manifestations, ranging from elevated liver enzymes to the

development of a liver capsule hematoma.� Acute fatty liver

of pregnancy is widely known to mimic the clinical picture

of severe preeclampsia with major manifestations of liver

failure.� Both fatty acid metabolism and ACE abnormalities

have been associated with this pathology.2,3

We present the case of a primigravid woman with severepreeclampsia at 34 weeks’ gestation and abnormal liverfunction. Postpartum genetic assessment showed that theseconditions resulted from homozygosity for two of theenzymes involved in fatty acid metabolism, as well as a carrierstate for an ACE deletion.

THE CASE

A previously well 28-year-old woman, gravida 1 para 0, hadsevere hyperemesis that persisted until the time of delivery.She was seen in the emergency department many timesbecause of vomiting, but was discharged each time afterfluid replacement and administration of antiemetics.

This pregnancy was complicated by several episodes ofabdominal pain, referred to the epigastric area, with vomitingand anorexia. Multiple assessments using abdominal imaging(ultrasound/CT scan) and hematology profiles during thesecond and third trimester showed no abnormality. The

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CASE REPORT

Key Words: Preeclampsia, angiotensin converting enzyme, ACE,short-chain acyl-coenzyme A dehydrogenase, SCAD

Competing Interests: None declared.

Received on November 17, 2009

Accepted on January 20, 2010

patient presented to her obstetrician at 33+2 weekscomplaining again of epigastric pain and was found to havean elevated blood pressure of 150/93. She was admitted tohospital.

On the day of admission, a 24-hour urine collectionrevealed 616 mg of protein that increased to 1390 mg thenext day. The patient’s blood pressure normalized with theuse of oral long-acting nifedipine. Laboratory assessmenton admission showed normal levels of liver enzymes andplatelets. Abdominal ultrasound showed oligohydramniosand a healthy fetus with an estimated fetal weight at the 40thpercentile.

The patient continued to complain of right upper quadrantpain and headache. She was given betamethasone to accel-erate fetal lung maturation. On the second hospital day, theabdominal pain and headache persisted. On the thirdhospital day, 48 hours after administration ofbetamethasone, labour was induced because of persistentsevere preeclampsia with blood pressure of 160/100,elevated liver enzymes (serum AST 700 U/L, serum ALT1000 U/L) and headaches. She delivered a 1700 g baby boyvaginally.

On the day of delivery, serum AST was 1500 U/L andserum ALT was 2400 U/L. On the same day, the patientcomplained of a fixed single blind spot on her left eye.Investigations four hours later showed a low serumfibrinogen of 134 mg/dL, INR of 1.5, a platelet concentrationof 34 × 109/L, a hemoglobin concentration of 9 g/L, ahematocrit of 29%, and a serum glucose level of 90 mg/dL.Treatment with magnesium sulfate and oral nifedipine wascontinued, with systolic blood pressures averaging 130 to140 mm Hg and diastolic pressures averaging 80 to 90 mmHg. Ophthalmologic assessment showed macular edemaand hypertensive retinopathy.

A CT scan of the abdomen on the second postpartum dayrevealed intrahepatic cholestasis, but no other abnormality.

On the third postpartum day, an increase in platelet countto 68 × 109/L was identified; serum fibrinogen increased to

225 mg/dL, the INR decreased to 1.3, and the hematocritremained stable at 29%. Serum AST reduced to 1100 U/L,and serum ALT reduced to 1500 U/L.

The patient reported no further epigastric or right upperquadrant pain by the fifth postpartum day. Her conditioncontinued to improve, and she was discharged on the seventhpostpartum day.

On subsequent genetic assessment, this patient was foundto be a homozygote for a common variant SCHAD mutation625 G to A, a homozygote for the common variant ACEgene deletion (Alu I/D in intron 16), and a carrier of anLCHAD polymorphism. Further testing showed that herson was also homozygous for SCHAD. The patient’s partnerwas tested and proved to be heterozygous for the SCHADmutation.

DISCUSSION

Fatty acids are the primary source of fuel for the heart andthe brain, but enzymes are required for them to be con-verted into energy. These enzymes are classified, accordingto the length of the fatty acid chain that they oxidize, as verylong chain dehydrogenase, long chain dehydrogenase, andshort chain dehydrogenase. Abnormalities in the genes codingfor these enzymes result in an abnormally functioningenzyme. In such cases, clinical manifestations may varyfrom subtle hypoglycemia with ketosis to frank myopathyand even death.4 Other manifestations include recurrentupper abdominal pain due to lactic acidosis with normalhematologic parameters. CT scanning may show intra-hepatic cholestasis.4

There have been several published reports of acute fattyliver of pregnancy with an abnormal genotype for theseenzymes.4–6 None of these have included the abnormalitiesidentified in the case we describe. The main feature inhistologic assessment in these cases is the deposition of fatdroplets distorting the liver architecture. The clinical mani-festations in these cases are thought to be the product ofliver failure due to destruction or necrosis of hepatocytes.5

The patient in our case complained of recurrent abdominalpain even before pregnancy, with normal findings onabdominal imaging and hematologic assessment. Thepostpartum CT scan showed intrahepatic cholestasis, whichhas been also associated with LCHAD deficiency.

The angiotensin converting enzyme transforms angiotensinI to angiotensin II, which is a potent vasoconstrictor.Angiotensin II is also involved in the inactivation of vasodi-lators such as bradykinins. Abnormalities in gene coding forthis enzyme have been associated with severe preeclampsia.7

CASE REPORT

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ABBREVIATIONS

ACE angiotensin converting enzyme

ALT alanine aminotransferase

AST aspartate aminotransferase

INR International Normalized Ratio

LCHAD long chain dehydrogenase

SCHAD short chain dehydrogenase

It has been hypothesized that being a carrier of fatty acidenzyme deficiency may be associated with placentalpathology because of the toxic nature of excessive fattyacids.8 Prolonged fasting can trigger the clinicalmanifestations of fatty acid enzyme deficiency. The worseningcondition of the patient in our case immediately after deliv-ery may have been related to the stress of labour, as well asprolonged fasting.

Despite the low incidence of the condition, it is reasonableto suggest that women who present with symptoms ofsevere preeclampsia and marked abnormalities of liverfunction should be screened for fatty acid enzymeabnormalities.

Further, if the patient is a carrier for a mutation, her infantmay be at risk for later development of metabolicabnormalities. This condition predicts adverse pregnancyoutcomes in future pregnancies, and thus close surveillanceis recommended.

ACKNOWLEDGEMENTS

The woman whose story is told in this case report hasprovided written consent for its publication.

REFERENCES

1. Creasy R, Frazier L, Resnik R, Iams J, Lockwood C, Moore T,eds. Maternal fetal medicine principles and practice. 6th ed. Philadelphia:Saunders Elsevier; 2009.

2. Gurdol F, Isbilen E, Yilmaz H, Isbir T, Dirican A. The association betweenpreeclampsia and angiotensin-converting enzyme insertion/deletionpolymorphism. Clin Chim Acta 2004;341:127–31.

3. Choi H, Kang JY, Yoon HS, Han SS, Whang CS, Moon IG, et al.Association of Angiotensin-converting enzyme and angiotensinogen genepolymorphisms with preeclampsia. J Korean Med Sci 2004;19:253–7.

4. den Boer M, Wanders R, Morris A, Heymans H, Wijburg F. Long-chain3 hydroxyacyl-coa dehydrogenase deficiency: clinical presentation andfollow up of 50 patients. Pediatrics 2002;109:99–104.

5. Oey NA, den Boer M, Ruiter JP, Wanders R, Duran M, Waterham H, et al.High activity of fatty acid oxidation enzymes in human placenta:implications for fetal maternal disease. J Inherit Metab Dis 2003;26:385–92.

6. Tyni T, Ekholm E, Pihko H. Pregnancy complications are frequent in longchain 3 hydroxyacyl coenzyme A dehydrogenase deficiency. Am J ObstetGynecol 1998;178: 603–8.

7. Matern D, Hart P, Murtha AP, Vockley J, Gregersen N, Millington DS, et al.Acute fatty liver of pregnancy associated with short-chain acyl-coenzymeA dehydrogenase deficiency. J Pediatr 2001;138:585–8.

8. Bouba I, Makrydimas G, Kalaitzidis R, Lolis DE, Siamopoulos KC,Georgiou I. Interaction between the polymorphisms of therenin-angiotensin system in preeclampsia. Eur J Obstet GynecolReprod Biol 2003;110:8–11.

A Case of Severe Preeclampsia Leading to the Diagnosis of De Novo Abnormal Fatty Acid Metabolism and ACE Gene Deletion

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