Clinical Signs and Symptoms


Citrin deficiency may cause a very diversified presentation of symptoms in different patients. Patients may have one or more symptoms at different onsets. Not all the patients would have all the symptoms at each onset.

​Neonatal Intrahepatic Cholestasis (NICCD) (age <1)

Possible symptoms:

  • Neonatal hepatic cholestasis
  • Growth stagnation 
  • Hepatomegaly
  • Diffuse fatty liver and parenchymal cell infiltration

NICCD is usually not severe and the symptoms generally resolved by age of one with proper treatment. In some rare cases it could be fatal due to infection and liver cirrhosis. Some of them may even need a liver transplant. [Kobayashi, Saheki et al 2014]

Starting around age one to two years, children show a strong preference for protein-rich and lipid-rich foods and an aversion to sugar-rich and carbohydrate-rich foods [Hachisu et al 2005, Saheki & Kobayashi 2005, Saheki et al 2008].

Citrullinemia Type II (CTLN2)

Severe Onset :

  • Recurrent Hyperammonemia (raised ammonia level)
  • Neuropsychiatric symptoms: delirium, aggressiveness, irritability, hyperactivity, disorientation, agitation, drowsiness, memory loss, tremors, convulsions and coma
  • In some cases, patient develops cerebral edema which can lead to death

​​Other possible presentations :​

  • Hepatoma, pancreatitis, hyperlipidemia(raised lipid level), fatty liver
  • Low BMI
  • Strong food preference (prefer protein, fat and dislike carbohydrate, feel sick after taking alcohol)

​In the second or later decades, some individuals with citrin deficiency develop severe CTLN2 with neuropsychiatric symptoms [Saheki & Kobayashi 2002]. Typically the transition from the adaptation (and/or compensation) stage following NICCD to the onset of CTLN2 is gradual. [Kobayashi, Saheki, et al 2014]

​CTLN2 onset could be sudden. The symptoms are often triggered by alcohol and sugar consumption, medication and/or surgery. And affected individuals may or may not have a previous history of NICCD or FTTDCD.

​Not every citrin deficiency patient will develop CTLN2. In fact, most patients do not develop CTLN2 with proper diet management and follow-ups. Please see more details under Incidence of the Condition.

Failure to Thrive and Dyslipidemia (FTTDCD) 

Possible symptoms:

  • Show preference for protein rich and / or lipid rich foods
  • Aversion to carbohydrate rich foods
  • Growth Retardation
  • Hypoglycemia (low blood sugar level)
  • Fatigue
  • Hyperlipidemia (raised lipid level)
  • Pancreatitis
  • Fatty Liver
  • Hepatoma

​​FTTDCD has recently been proposed as a novel post-NICCD phenotype before the onset of CTLN2 [Song et al 2011]. The clinical and laboratory features of FTTDCD are still being elucidated. During this period (traditionally assumed to be an “apparently healthy” stage before CTLN2 onset) some children were found to have laboratory and/or clinical abnormalities. [Kobayashi, Saheki et al 2014]

​FTTDCD has not been generally observed among post-NICCD patients.


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Citrin Foundation, set up in 2016 to tackle citrin deficiency, aims to provide end-to-end support to all citrin deficiency patients, from funding research that drives effective treatments and eventually cure, and provide support to patients and families. We are a patient-driven, not-for profit organization.

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