Neonatal intrahepatic cholestasis due to citrin deficiency

What it is

From: Orphanet

A mild subtype of citrin deficiency characterized clinically by low birth weight, failure to thrive, transient intrahepatic cholestasis, multiple aminoacidemia, galactosemia, hypoproteinemia, hepatomegaly, decreased coagulation factors, hemolytic anemia, variable but mostly mild liver dysfunction, and hypoglycemia.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal circulating lipid concentration · Very frequent (99-80%)

Any deviation from the normal concentration of lipid in the blood circulation.

Cholestasis · Very frequent (99-80%)

Impairment of bile flow due to obstruction in bile ducts.

Decreased circulating antibody level · Very frequent (99-80%)

An abnormally decreased level of immunoglobulin in blood.

Elevated alpha-fetoprotein · Very frequent (99-80%)

The concentration of alpha-fetoprotein in the blood circulation is above the upper limit of normal.

Elevated circulating alkaline phosphatase concentration · Very frequent (99-80%)

Abnormally increased serum levels of alkaline phosphatase activity.

Elevated gamma-glutamyltransferase level · Very frequent (99-80%)

Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.

Elevated plasma citrulline · Very frequent (99-80%)

The concentration of citrulline in the blood circulation is above the upper limit of normal.

Hyperbilirubinemia · Very frequent (99-80%)

An increased amount of bilirubin in the blood.

Hypergalactosemia · Very frequent (99-80%)

The concentration of galactose in the blood circulation is above the upper limit of normal.

Hypertriglyceridemia · Very frequent (99-80%)

The concentration of triglyceride in the blood circulation is above the upper limit of normal.

Hypoalbuminemia · Very frequent (99-80%)

The concentration of albumin in the blood circulation is below the lower limit of normal.

Increased circulating lactate dehydrogenase concentration · Very frequent (99-80%)

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

Jaundice · Very frequent (99-80%)

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

Lactic acidosis · Very frequent (99-80%)

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

Other findings in the same source

From: Orphanet

Additional reported features include Prolonged prothrombin time (Very frequent (99-80%)); Abnormal circulating alanine concentration (Frequent (79-30%)); Abnormality of arginine metabolism (Frequent (79-30%)); Abnormality of glutamine metabolism (Frequent (79-30%)); Diarrhea (Frequent (79-30%)); Elevated circulating hepatic transaminase concentration (Frequent (79-30%)); Hepatic steatosis (Frequent (79-30%)); Hepatomegaly (Frequent (79-30%)); Hepatosplenomegaly (Frequent (79-30%)); Hyperammonemia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Neonatal intrahepatic cholestasis due to citrin deficiency is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Neonatal intrahepatic cholestasis due to citrin deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.