[MIM 603 471

Very rare. Citrullinemia type II is a severe subtype of citrine deficiency (SLC25A13 gene (7q21.3)). Citrine is a carrier of aspartate/glutamate from the mitochondria (liver, kidney, intestine) to the cytosol for the synthesis of urea, proteins and nucleotides. It also intervenes in the gluconeogenesis from lactate in the urea cycle and in the transfer of NADH into the mitochondria.

Different forms:

-        neonatal intrahepatic cholestasis caused by deficiency in citrine (or NICCD for Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency): obstructive jaundice with hepatomegaly: sometimes: hypoglycemia, hemolytic anemia, cataracts. No hyperammonemia but galactosemia may be present. The symptoms disappear around the age of 12 months, but the disease can reappear in the adult form many years later. It is sometimes referred to as a quiescent form where patients are aymptomatic but often have an aversion to carbohydrates and consume a lot of protein.

-        the classic form occurs in adults (between 20 and 50 years of age) and is clinically characterized  by recurrent episodes of hyperammonemia (with increase of the plasma citrulline levels) and neuropsychiatric events such as nocturnal delirium, confusion or drowsiness, agitation, disorientation, memory loss, abnormal behaviour (aggression, irritability, and hyperactivity) convulsions and coma. These seizures can be caused by an infection, a medication or the ingestion of alcohol. Often, death occurs in a clinical picture of cerebral edema . Sometimes hypertriglyceridemia, cardiopathy and hepatomas. These patients often have an aversion to carbohydrates and are big consumers of proteins.

-        neonatal intrahepatic cholestasis by deficiency in citrine (or NICCD for Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency): obstructive jaundice with hepatomegaly: sometimes: hypoglycemia, hemolytic anemia, cataracts. No hyperammonemia but a galactosemia may be present. The symptoms disappear around the age of 12 months, but the disease can reappear as an adult form many years later.

Curative treatment: liver transplant.

Symptomatic treatment: a carbohydrate-poor and protein-rich diet. Attention: in case of acute crisis,  the administration of carbohydrates or  glycerol (to decrease cerebral edema) worsens the situation

Anesthetic implications:

monitor the  blood level of glucose and ammonium; avoid IV Ringer's lactate as it can induce hyperlactatemia.

References :

-        Cano A,Valayannopoulos V.
Nouvelles pathologies,
In  Maladies métaboliques héréditaires, éd B Chabrol et P de Lonlay,  p159-75, Doin 2011 

-        Tao K-M, Shen L, Sun Y-M.
Lactate-buffered solutions in patients with citrin deficiency.
Can J Anesth 2022 ; 69 :786-7.

Updated: July 2022