Metabolic liver diseases presenting with neonatal cholestasis: at the crossroad between old and new paradigms
Metabolic liver diseases (MLD) are an important group of disorders presenting with neonatal cholestasis (NC). The spectrum of liver involvement is wide and the presumptive diagnosis is traditionally based on clinical and laboratory findings. Recently, next-generation sequencing (NGS) panels have emerged as an appealing tool to diagnose neonatal/infantile cholestatic disorders. The aim of this study was to identify clinical phenotypes of liver injury and contribute to find a diagnostic methodology that integrates new molecular diagnostic tools. We retrospectively analyzed the clinical and biochemical features of 16 patients with MLD and NC. Patients were categorized into three groups: A—NC with liver failure (N = 8): tyrosinemia type I (n = 2), classic galactosemia (n = 5), mitochondrial DNA depletion syndrome (n = 1); B—NC evolving with chronic liver disease (N = 5): argininemia (n = 2); mitochondrial cytopathy (n = 1); congenital disorders of glycosylation type Ia (n = 1); Zellweger syndrome (n = 1); and C—transient NC (N = 3): Niemann-Pick type C (n = 2), citrullinemia type II (n = 1).
What is Known:
• Metabolic liver diseases are an important group of disorders presenting with neonatal cholestasis.
• The diagnostic approach is challenging and traditionally based on clinical and laboratory findings. Next-generation sequencing is a recent and rapidly developing tool in pediatric hepatology.
What is New:
• We provide a liver-targeted characterization of metabolic liver diseases presenting with neonatal cholestasis, categorizing them into three clinical phenotypes that may narrow the diagnostic possibilities.
• A clinical decision-making algorithm is proposed, in which the NGS technology is integrated.
KeywordsNeonatal cholestasis Transient neonatal cholestasis Liver failure Metabolic liver diseases Next-generation sequencing panels
Congenital disorder of glycosylation
Inborn errors of metabolism
International normalized ratio
Metabolic liver diseases
Niemann-Pick type C
Orthotopic liver transplant
Progressive familiar intrahepatic cholestasis
Helena Moreira Silva: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript.
Inês Maio: acquisition of data, analysis and interpretation of data.
Anabela Bandeira and Esmeralda Martins: patient diagnosis and follow-up, analysis and interpretation of data; critical revision of the manuscript.
Ermelinda Santos Silva: patient diagnosis and follow-up, study concept and design; study supervision; critical revision of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by our institutional scientific and ethics committee [Study N/REF.ª 2016. 081 (069-DEFI/066-CES)].
Clinical trial registration
Informed consent was obtained from all individual participants included in the study.
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