enar
enar
21
Nov

A Case Report on Rare Gestational Alloimmune Liver Disease (GALD)

By
,
0

Introduction

Gestational Alloimmune Liver Disease (GALD), formerly referred to as neonatal hemochromatosis or neonatal iron storage disease, is a rare disorder characterized by severe hepatic failure and iron deposition in both hepatic and extrahepatic tissues (hemosiderosis) during the fetal and neonatal periods. It is thought to result from an abnormal maternal immune response, similar to that seen in neonatal hemolytic disease, whereby maternal IgG antibodies cross the placenta, activating the complement cascade in the fetus and leading to hepatic injury.

A high immunohistochemical staining level for the human C5b-9 complex (the terminal complement cascade) is considered a hallmark diagnostic feature of GALD, alongside elevated serum ferritin and alpha-fetoprotein levels.

This report presents the clinical course of a six-day-old infant initially diagnosed with jaundice due to blood group incompatibility, whose condition rapidly progressed to lethargy, systemic depression, visceromegaly, edema, and seizures. The final diagnosis was revised to gestational alloimmune liver disease.

Clinical case presentation

Patient Information

  • Age and Gender: Male, 6 days old at admission.
  • Medical History:
    • Unknown antenatal and perinatal history, since the delivery took place at another hospital without discharge documentation.
    • Mather’s blood group: B negative.
    • Previous sibling death at two years of age due to acute liver failure.

Clinical History

The infant developed jaundice within hours of birth. Initial investigations revealed Rh blood group incompatibility. Blood exchange transfusions were performed twice using B-negative blood within the first 24 hours, combined with intensive phototherapy. Over subsequent days, the infant developed lethargy, systemic depression, visceromegaly, pitting edema, then seizures by the fourth day.

Laboratory results indicated anemia, thrombocytopenia, and coagulopathy, necessitating plasma and platelet transfusions. Deterioration led to referral to the Neonatal Intensive Care Unit (NICU).

Clinical Examination upon Admission

  • General condition: Poor, with marked lethargy, systemic depression, and a tendency to sleep.
  • Neurological examination: Absence of sucking and Moro reflexes.
  • Cardiovascular system: Presence of a grade 2/6 cardiac murmur.
  • Respiratory: Normal gas exchange.
  • Digestive system: Severe jaundice with palpable hepatosplenomegaly.
  • Extremities Pitting edema with palpable peripheral pulses.
  • No external dysmorphic features or significant anomalies.

Diagnostic Workup

Investigations at Referring Hospital

  • Before First Exchange Transfusion:
    • Hemoglobin (Hb): 8.3 g/dL (normal range: 14-20 g/dL).
    • Total bilirubin: 17.3 mg/dL (normal range: less than 12 mg/dL)
    • Indirect bilirubin: 11.3 mg/dL, (normal range often less than 1 to 5 mg/dL)
  • After the first blood Transfusion:
    • Hemoglobin (Hb): 12.6 g/dL.
    • Total bilirubin: 17.5 mg/dL.
    • Indirect bilirubin: 12.2 mg/dL, (normal range often less than 1-5 mg/dL)
  • After the second blood Transfusion:
    • Hemoglobin (Hb): 15.3 g/dL.
    • Total bilirubin: 12.3 mg/dL (normal range: less than 12 mg/dL)
    • Indirect bilirubin: 10.45 mg/dL, (normal range often less than 1 to 5 mg/dL)
    • Direct bilirubin: 1.85 mg/dL (normal less than 1 mg/dL)
    • CRP: 30 mg/dL, (normal less than 1 mg/dL)
    • Prothrombin (PT) time: 22 seconds, (normal 10-14 seconds)

Investigations at the NICU

  • Hemoglobin: 14.2 g/dL.
  • Number of platelets: 60,000 μL (normal range: 150,000-400,000).
  • Direct bilirubin: 5.1 mg/dL (normal range: less than 1 mg/dL)
  • Albumin: 2.6 g/dL (normal range: 3.5-5.4 g/dl).
  • Ferritin: 1981 ng/ml (normal range: 25-200).
  • Potassium (K): 3.3 mmol/L (normal range: 3.5-5.0 mmol/L).
  • Calcium (Ca): 3.26 mg/dL (normal range: 9-11 mg/dL)

Arterial blood gases:

  • pH:7.5 (normal range: 7.35-7.45)
  • pCO2: 39 mm Hg (normal range: 35-45 mm Hg).
  • HCO3: 37 mmol/L (normal range: 22-28 mmol/L).

Note: All standard diagnostic evaluations were conducted, yielding results within normal parameters; however, these findings were not detailed in the case report.

Other Investigations:

  • Cranial CT: Mild subdural hemorrhage.
  • Echocardiography: Small patent ductus arteriosus (PDA) And Patent Foramen Oval (PFO).
  • Abdominal Ultrasound: Hepatosplenomegaly.

Differential diagnosis

After the surveys, differential diagnoses included:

  1. Gestational Alloimmune Liver Disease (GALD)
  2. Graft-versus-host disease (GVHD)
  3. Hemophagocytic lymphohistiocytosis (HLH)
  4. Mitochondrial or metabolic disorders
  5. TORCH infections
  6. Fetal ischemia

Definitive diagnosis

Gestational Alloimmune Liver Disease (GALD)

Management

Therapeutic interventions

  • Transfusion: Blood exchange was performed twice.
  • Intravenous Immunoglobulin (IVIG): Administered at 1 g/kg, with a second dose the following day.
  • Ursodeoxycholic Acid: 20 mg/kg daily to improve bile flow.
  • Temporary Suspension of Breastfeeding: To prevent maternal IgG transfer through breast milk during treatment.

Treatment response

  • Significant reduction in bilirubin levels with gradual clinical improvement.
  • Progressive resolution of visceromegaly.

Outcomes and follow-up

  • Discharge: The infant was discharged after five days of IVIG treatment, with near-complete resolution of visceromegaly.
  • Laboratory Results at Discharge:
    • Hemoglobin: 12.5 g/dL
    • Platelets: 192,000/µL
    • Total Bilirubin: 2 mg/dL
  • Follow-Up After One Week: The infant showed significant improvement and was in good health.

Recommendations

Administration of IVIG in future pregnancies, starting from the 14th week of gestation until delivery is recommended to reduce recurrence risk.

Discussion

GALD originates during fetal life due to transplacental maternal IgG antibodies targeting fetal hepatic antigens, leading to severe liver inflammation and dysfunction. Exchange transfusion aims to reduce pathogenic antibodies, while IVIG prevents further damage. This case illustrates the typical clinical presentation of GALD, emphasizing the importance of early diagnosis and timely intervention to improve outcomes and reduce mortality associated with this disorder.

Conclusion

Early diagnosis and prompt immunotherapy are pivotal in improving outcomes and reducing mortality rates in GALD. Increasing medical awareness of this rare condition is essential to ensure timely recognition and appropriate management.

Acknowledgment

This case was managed at Hand in Hand Children and Women’s Hospital, supported by Hand in Hand for Relief and Development, by pediatric residents Dr. Sateef Al-Ahmad and Dr. Ahmad Al-Kurdi, under the supervision of neonatologist in the Syrian Board of Medical Specialties SBOMS Dr. Abdulmohsen Al-Hassan .

References

[1] A. Wehrman MD and K. M Loomes MD, “Causes of cholestasis in neonates and young infants,” 2024, UpToDate. [Online]. Available: https://www.uptodate.com/contents/causes-of-cholestasis-in-neonates-and-young-infants?search=gestational%20alloimmune%20liver%20disease&source=search_result&selectedTitle=2%7E4&usage_type=default&display_rank=2%23H23
[2] A. G. Feldman and P. F. Whitington, “Neonatal hemochromatosis,” Dec. 2013. doi: 10.1016/j.jceh.2013.10.004.







Recent Comments