Diagnosis

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How is Citrin Deficiency Diagnosed?

Diagnosis is based on clinical and biochemical analysis. Biochemical analysis shows hyperammonemia (raised ammonia level), altered blood profile of amino acids with increased concentration of citrulline and arginine as well as threonine/serine ratio.

The diagnosis is confirmed by mutational study of the SLC25A13 gene. [Tsuboi et al 2001, Mutoh et al 2008]

1. Diagnostic Algorithm Illustration

Kobayashi, Saheki et al 2014

Figure 1. Diagnostic Algorithm of Citrin Deficiency

Diagnostic Algorithm Illustration: Citrin Deficiency

Note that food preferences (e.g., aversion to sugars) are important in the diagnosis of citrin deficiency, not only in typical CTLN2 but also in cases of growth retardation, hypoglycemia, pancreatitis, hypertriglyceridemia (etc.) in both children and adults 

2. Flow Chart for Diagnosis of Citrin Deficiency in Neonatals and Children

Kobayashi, Saheki et al 2014

Figure 2. Flow chart for diagnosis of citrin deficiency (Pagon RA et al. University of Washington, Seattle 1993 - 2017)

Flow chart for diagnosis of citrin deficiency

​TB = total bilirubin
DB = direct bilirubin
TBA = total bile acids
ALP = alkaline phosphatase
AFP = α-fetoprotein
PSTI = pancreatic secretory trypsin inhibitor

3. Abnormal Laboratory Findings

Table 1. Biochemical Findings in Citrin Deficiency by Phenotype
Phenotype (Age) Blood or Plasma Concentration of Ammonia (umol/L) Plasma or Serum Concentration of Citrulline (C)# Plasma or Serum Concentration of Arginine (A) (umol'L) Plasma or Serum Threonine-to-Serine Ratio Serum Concentration of Pancreatic Secretory Trypsin Inhibitor (PSTI)^ (ng/mL)
Control 18-47(*) 17-43(*) 54-130(*) 1.10 4.6-20(*)
NICCD (O-6 months) 60 300 205 2.29 30
FTTDCD Normal or slightly elevated Normal or slightly elevated Usually normal Unknown Unknown
CTLN2 152 418 198 2.32 71

Kobayashi et al 2006

# Citrullinemia, which can be detected on newborn screening, is the earliest identifiable biochemical abnormality of NICCD (Tamamori et al 2004).
^ Because the serum PSTI concentration is high in some individuals with NICCD (Tamamori et al 2002) and also in individuals before the onset of CTLN2 (Tsuboi et al 2001), the measurement of serum PSTI concentration may be useful in presymptomatic diagnosis of CTLN2.
*   Range

4. Pathologic Findings

These findings include fatty infiltration and mild fibrosis of the liver despite little or no liver dysfunction.

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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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