Related Experiment Video

Updated: Jul 29, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.7K

Infantile ATP7B-Related End-Stage Liver Disease: An Exceptional Wilson Disease Phenotype From Consecutive Generations

Emanuele Nicastro1, Maria Iascone2, Angelo Di Giorgio1

  • 1From the Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.

JPGN Reports
|May 19, 2023
PubMed

Insights

Wilson disease (WD) is a rare genetic disorder of copper metabolism. This case highlights an infant with Wilson disease presenting with neonatal cholestasis, suggesting intrauterine copper overload due to maternal undiagnosed WD.

Area of Science:

  • Genetics
  • Hepatology
  • Pediatrics

Background:

  • Wilson disease (WD) is an autosomal recessive disorder of copper metabolism.
  • It typically manifests after three years of age.

Observation:

  • A female infant presented with neonatal cholestasis, rapidly progressing to end-stage liver disease.
  • Clinical features included hepatosplenomegaly, neurological impairment, hemolytic anemia, and central hypothyroidism.
  • Whole exome sequencing revealed homozygous ATP7B mutations in the infant and heterozygous mutations in the mother.

Findings:

  • The patient had a homozygous ATP7B mutation (p.Gln7fs/p.His1069Gln), confirming Wilson disease.
  • The mother carried a heterozygous ATP7B mutation (p.His1069Gln/p.His1069Gln) and was diagnosed with cirrhotic WD.
  • Elevated liver copper levels (7-fold increase) and characteristic gene expression patterns supported copper toxicity due to ATP7B loss of function.

Implications:

  • This case represents an exceptionally early presentation of Wilson disease, potentially due to combined genetic factors and intrauterine copper overload.
  • Highlights the importance of considering WD in neonatal cholestasis, even with atypical presentations.
  • Suggests that maternal undiagnosed WD can contribute to severe intrauterine copper overload in offspring.

Keywords:
consecutive generationscopperliver transplantationneonatal cholestasisnext generation sequencing

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

9.8K
Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine09:54

Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine

Published on: November 4, 2018

8.2K

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
Inborn Errors of Metabolism01:20

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
207
Pedigree Analysis01:35

Pedigree Analysis

Overview
84.5K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.7K
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.7K
Smooth Endoplasmic Reticulum01:21

Smooth Endoplasmic Reticulum

Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.9K