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Disease Profile

Neonatal intrahepatic cholestasis caused by citrin deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

E72.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NICCD; Neonatal-onset citrullinemia type II; Citrin deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; RDCRN

Summary

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. This leads to transient intrahepatic cholestasis and variable liver dysfunction in children younger than one year of age. NICCD is generally not severe, and symptoms disappear by age one year with appropriate treatment. Years or even decades later, however, some of these individuals develop the characteristic features of adult-onset type II citrullinemia. NICCD is caused by mutations in the SLC25A13 gene. This condition is inherited in an autosomal recessive pattern.[1]

Symptoms

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by transient intrahepatic cholestasis, diffuse fatty liver, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, decreased coagulation factors, hemolytic anemia, hepatomegaly, variable liver dysfunction, and/or hypoglycemia in children younger than one year of age. NICCD is generally not severe, and symptoms typically disappear by age one year with appropriate treatment. At around age two, children with NICCD begin to show a particular fondness for protein-rich and fatty foods and an aversion to sugary and carbohydrate-rich foods. One of more decades later, some of these individuals develop neuropsychiatric symptoms characteristic of adult-onset citrullinemia type II.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Decreased circulating antibody level
0004313
Elevated alkaline phosphatase
Greatly elevated alkaline phosphatase
High serum alkaline phosphatase
Increased alkaline phosphatase
Increased serum alkaline phosphatase

[ more ]

0003155
Elevated alpha-fetoprotein
0006254
Elevated gamma-glutamyltransferase level
0030948
Elevated plasma citrulline
0011966
Hyperbilirubinemia
High blood bilirubin levels
0002904
Hypergalactosemia
0012024
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Hypoalbuminemia
Low blood albumin
0003073
Increased lactate dehydrogenase level
0025435
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Lactic acidosis
Increased lactate in body
0003128
Prolonged prothrombin time
0008151
30%-79% of people have these symptoms
Abnormal circulating alanine concentration
0010916
Abnormal circulating arginine concentration
0010909
Abnormal circulating glutamine concentration
0010903
Diarrhea
Watery stool
0002014
Elevated hepatic transaminase
High liver enzymes
0002910
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Hepatomegaly
Enlarged liver
0002240
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hyperammonemia
High blood ammonia levels
0001987
Hyperlysinemia
Elevated blood lysine
0002161
Hypertyrosinemia
Increased tyrosine in blood
0003231
5%-29% of people have these symptoms
Abnormal circulating serine concentration
0012278
Anemia
Low number of red blood cells or hemoglobin
0001903
Decreased HDL cholesterol concentration
Decreased circulating high-density lipoprotein cholesterol
Decreased HDL cholesterol
Low HDL-cholesterol

[ more ]

0003233
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hypermethioninemia
Increased methionine in blood
0003235
Hyperthreoninemia
High blood threonine levels
0003354
Increased LDL cholesterol concentration
Increased circulating LDL level
Increased LDL cholesterol

[ more ]

0003141
Increased urinary glycerol
0040301
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Ketonuria
0002919
Poor appetite
Decreased appetite
0004396
1%-4% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Intrahepatic cholestasis
0001406

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

    Treatment

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • GeneReviews provides a current, expert-authored, peer-reviewed, full-text article urea cycle disorders in general that you may find helpful. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus.gov provides more information on urea cycle disorders in general. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
        • Genetics Home Reference (GHR) contains information on Neonatal intrahepatic cholestasis caused by citrin deficiency. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Neonatal intrahepatic cholestasis caused by citrin deficiency. Click on the link to view a sample search on this topic.

            References

            1. Citrullinemia. Genetics Home Reference (GHR). 2017; https://ghr.nlm.nih.gov/condition/citrullinemia.
            2. Kobayashi K, Saheki T. Citrin Deficiency. GeneReviews. July 31, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1181/.

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