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Pediatrics53 papers

Metabolic and genetic disorder affecting the liver

Last edited: 4/15/2026

Overview

GRACILE syndrome is a lethal autosomal recessive disorder characterized by fetal growth retardation, lactic acidosis, Fanconi-type aminoaciduria, cholestasis, hepatic iron overload, and early neonatal death 1.

Diagnosis

  • Clinical Presentation: Growth retardation, lactic acidosis, aminoaciduria, cholestasis 1.
  • Laboratory Tests: Elevated aminoaciduria, liver function tests indicative of cholestasis, metabolic acidosis 1.
  • Imaging: Abdominal imaging may reveal hepatomegaly or other organ involvement 1.
  • Biopsy/Autopsy Findings: Histopathological evidence of cholestasis, iron overload in hepatocytes and Kupffer cells, and pancreatic atrophy 1.
  • Management

  • Supportive Care: Focus on managing symptoms such as metabolic acidosis, hydration, and nutritional support 1.
  • Genetic Counseling: Essential for families with affected individuals to understand recurrence risks 1.
  • No Specific Therapies: No curative treatments identified; management is primarily supportive 1.
  • Special Populations

  • Pediatrics: Condition manifests early in infancy with high mortality within the first month of life 1.
  • Comorbidities: Often associated with renal tubular dysgenesis and pancreatic insufficiency 1.
  • Key Recommendations

  • Early Recognition and Supportive Care: Prompt identification and management of metabolic derangements and supportive care measures are crucial for improving quality of life (Evidence: Moderate 1).
  • Genetic Testing and Counseling: Offer genetic testing and counseling to affected families to understand disease inheritance and recurrence risks (Evidence: Expert opinion 1).
  • Monitoring Organ Involvement: Regular monitoring of liver, kidney, and pancreatic function is recommended given multisystem involvement (Evidence: Moderate 1).
  • References

    1 Rapola J, Heikkilä P, Fellman V. Pathology of lethal fetal growth retardation syndrome with aminoaciduria, iron overload, and lactic acidosis (GRACILE). Pediatric pathology & molecular medicine 2002. link

    Original source

    1. [1]
      Pathology of lethal fetal growth retardation syndrome with aminoaciduria, iron overload, and lactic acidosis (GRACILE).Rapola J, Heikkilä P, Fellman V Pediatric pathology & molecular medicine (2002)

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