It is not often that two medical disciplines come together, but when they do, our knowledge of both is enriched. In this article, we will be discussing 1 of 2 case studies of pregnant women with Alagille syndrome (ALGS) presented in a study written by Morton and Kumar and published in Obstetric Medicine.

The case study will be presented in concise bullet points for easy readability.

Presentation

  • A 29-year-old woman who was pregnant for the first time was transferred to their center at 20 weeks’ gestation due to hypertension, proteinuria, and abnormal renal function.
  • She had only a past medical history of polycystic ovary syndrome and was not on any medication. 
  • Her family history revealed that her adolescent half-sister had died following liver transplantation for ALGS. 

Investigations

  • Physical examination revealed a body mass index of 34 kg/m2 (obese) and blood pressure of 150/100 mm Hg. 
  • Chest auscultation revealed an ejection systolic murmur. 
  • Her blood and urine investigations were as follow:
    • Serum creatinine: 111 mmol/L (normal range: 30-70 micromol/L)
    • Alanine transaminase: 61 U/L (normal range: 5-30U/L)
    • Aspartate transaminase: 39 U/L (normal range: 5-30U/L) 
    • Urine protein:creatinine ratio (PCR): 179 mg/mmol (normal range: 0-15mg/mmol).
  • Abdominal ultrasound showed normal hepatobiliary structures. Bilateral renal cortical thinning could be observed. Renal artery stenosis was absent. 
  • Further investigations excluded pheochromocytoma, primary aldosteronism, obstructive sleep apnea, and vasculitis. 
  • Maternal echocardiography demonstrated increased flow velocity through the right pulmonary artery branch, which was suggestive of minor narrowing.

Treatment and Progression

  • Labetalol 200 mg twice a day was started for persistent hypertension. 
  • Generalized pruritus developed at 33 weeks’ gestation. The patient was started on ursodeoxycholic acid 1500 mg/day, with resolution of itch.
  • Serial fetal growth scans reveal progressive fetal growth restriction. 
  • At 36 weeks’ gestation, she developed a significant increase in blood pressure. Serum creatinine and urine PCR suggested a picture of superimposed preeclampsia, which prompted physicians to induce labor.
  • Serum bile acids were found to be normal.

Delivery 

  • A live male infant weighing 2014 g (about 4.4 lbs) was delivered. 
  • The placental weight was 279 g (3rd–5th percentile for gestational age). There was evidence of retroplacental hemorrhages and chronic villitis. The fetal/placental weight ratio was 7.2. 
  • Neonatal investigations revealed conjugated hyperbilirubinemia, elevated hepatic transaminases, and elevated gamma-glutamyl transferase. 
  • Neonatal echocardiography demonstrated mild pulmonary valve stenosis and hypoplasia of the branch pulmonary arteries. 
  • Neonatal renal ultrasound revealed multiple small echogenic medullary foci. 
  • Genetic testing of the neonate revealed heterozygosity in the JAG1 gene for a variant designated c.1153del,p.His385Thrfs*27. 
  • At the time of publication, the results for the genetic testing for the mother were pending. 

A Dangerous Pregnancy 

Morton and Kumar wrote, “Including the two cases detailed in this manuscript, there have been a total of only 11 successful pregnancies in women with ALGS described in the literature. Of these, fetal growth restriction was present in seven pregnancies (64%), pre-eclampsia in two pregnancies (18%), and one case of postpartum maternal pulmonary edema. Neonatal death following cardiac surgery occurred in one case.” 


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The extremely low known number of successful pregnancies among women with ALGS strongly suggests that ALGS causes conditions that are unfavorable for successful pregnancies. Morton and Kumar hypothesize that among the postulated causative factors for fetal growth restriction in women with ALGS are toxicity from bile acids and maternal vascular disease. 

Read more about ALGS etiology

Because ALGS is mostly inherited in an autosomal dominant manner, genetic counseling becomes important so that the parents fully understand the odds of their child inheriting the disease. Perge and Igaz, in their study on family screening and genetic counseling, wrote, “The main function of genetic counseling is the transfer of important pieces of information to the patient about the congenital or later-manifesting diseases. This process via informed consent should give enough information to the patient and the relatives to make decisions about the disease.” 

Adequate attention should be given to the woman with ALGS who intends to become pregnant. Morton and Kumar recommend that a number of factors are given due consideration before pregnancy, such as the patient’s extent of cardiac disease, and the presence of liver diseases such as cirrhosis or portal hypertension. In addition, patients should be advised that there is evidence that maternal cholestasis “may be associated with increased risk of fetal compromise, spontaneous preterm birth, and stillbirth,” they wrote. 

Read more about ALGS patient education

The ultimate aim of any genetic counseling is to answer a woman’s questions regarding her pregnancy, and to reassure her of the support available should she decide to become pregnant. The patient should be told of the kind of medical support available for a child born with ALGS, as well as the child’s expected quality of life and life expectancy.

“The chief goal of the genetic counseling is the prevention of the conception or the birth of a person who would suffer from a severe genetic disease and/or present information of the chance for having an affected descendant,” Perge and Igaz wrote. “If the prevention is not feasible, the alternative aim is to prevent the development of the consequences or to moderate its severity.”

References

Morton A, Kumar S. Alagille syndrome and pregnancyObstet Med. 2021;14(1):39-41. doi:10.1177/1753495X19849738

Perge P, Igaz P. Family screening and genetic counselingExp Suppl. 2019;111:29-32. doi:10.1007/978-3-030-25905-1_3