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 eme...

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Publicado en:European Journal of Pediatrics Vol. 178; no. 4; pp. 515 - 524
Autores principales: Moreira-Silva, Helena, Maio, Inês, Bandeira, Anabela, Gomes-Martins, Esmeralda, Santos-Silva, Ermelinda
Formato: Journal Article
Publicado: Springer Nature Apr2019
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00431-019-03328-5
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        atl: Metabolic liver diseases presenting with neonatal cholestasis: at the crossroad between old and new paradigms.
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        au:
          Moreira-Silva, Helena
          Maio, Inês
          Bandeira, Anabela
          Gomes-Martins, Esmeralda
          Santos-Silva, Ermelinda
        affil: Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte – CMIN, Centro Hospitalar Universitário do Porto, Largo da Maternidade de Júlio Dinis, 4050-651, Porto, Portugal
      sug:
        subj:
          Liver Failure, Acute Diagnosis
          Cholestasis Diagnosis
          Metabolism, Inborn Errors Diagnosis
          Sequence Analysis Methods
          Metabolism, Inborn Errors Complications
          Male
          Liver Failure, Acute Complications
          Female
          Metabolism, Inborn Errors Classification
          Infant, Newborn, Diseases
          Infant, Newborn
          Retrospective Design
          Infant
          Cholestasis Complications
          Scales
          Infant, Newborn: birth-1 month
          Infant: 1-23 months
          Male
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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