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European Journal of Pediatrics

, Volume 178, Issue 4, pp 515–523 | Cite as

Metabolic liver diseases presenting with neonatal cholestasis: at the crossroad between old and new paradigms

  • Helena Moreira-Silva
  • Inês Maio
  • Anabela Bandeira
  • Esmeralda Gomes-Martins
  • Ermelinda Santos-SilvaEmail author
Original Article

Abstract

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).

Conclusion: MLD presenting with NC can be categorized into three main clinical phenotypes of liver injury. We highlight transient NC as a clue for MLD that must be pursued. New molecular diagnostic tools can play a key role, but application criteria must be established to make them cost-effective.

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.

Keywords

Neonatal cholestasis Transient neonatal cholestasis Liver failure Metabolic liver diseases Next-generation sequencing panels 

Abbreviations

cB

Conjugated bilirubin

CDG

Congenital disorder of glycosylation

GGT

Gamma-glutamyltransferase

HE

Hepatic encephalopathy

IEM

Inborn errors of metabolism

INR

International normalized ratio

LF

Liver failure

MLD

Metabolic liver diseases

NBS

Newborn screening

NC

Neonatal cholestasis

NGS

Next-generation sequencing

NP-C

Niemann-Pick type C

OLT

Orthotopic liver transplant

PFIC

Progressive familiar intrahepatic cholestasis

Notes

Authors’ Contributions

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.

Ethical approval

The study was approved by our institutional scientific and ethics committee [Study N/REF.ª 2016. 081 (069-DEFI/066-CES)].

Clinical trial registration

Not applicable.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte – CMINCentro Hospitalar Universitário do PortoPortoPortugal
  2. 2.Pediatric Metabolic Unit, Centro Materno Infantil do Norte – CMINCentro Hospitalar Universitário do PortoPortoPortugal
  3. 3.Instituto de Ciências Biomédicas Abel SalazarPortoPortugal

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