Tyrosinemia Type I: FAH Gene Deletion/Duplication

Condition Description

Tyrosinemia Type I is an autosomal recessive inborn error of tyrosine metabolism [1]. In untreated children, it presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and renal tubular dysfunction associated with growth failure and rickets. Untreated children may have repeated, often unrecognized, neurologic crises that can include:

  • changes in mental status
  • abdominal pain
  • peripheral neuropathy
    • This may lead to liver failure, hepatocellular carcinoma, and potentially death before the age of ten years.

      Inclusion of tyrosinemia in the newborn screening panel has improved diagnosis of this condition and initiation of crucial therapy [2]. Combined treatment with nitisinone (orfadine) and a low-tyrosine/phenylalanine diet has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets.

      Tyrosinemia Type I results from deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). Typical biochemical findings include increased plasma and urine concentration of succinylacetone, elevated plasma concentrations of tyrosine, methionine, and phenylalanine, and elevated urinary concentration of tyrosine metabolites.

      The FAH enzyme is encoded by the FAH gene located at 15q23, and mutations to this gene are responsible for tyrosinemia by leading to reduced or absent FAH enzyme activity. The four common FAH mutations (IVS12+5 G&A, IVS6-1 G&T, IVS7-6 T&G, and P261L) account for approximately 60% of mutations in tyrosinemia type I in the general US population. The P261L mutation accounts for nearly 100% of mutations responsible for tyrosinemia type I in the Ashkenazi Jewish population [3]. IVS12+5 G&A accounts for 87.9% of mutations in the French Canadian population [4]. However, no genotype/phenotype correlation has been established [5]. Gene sequence analysis is available to test for mutations in the FAH gene.

Genes (1)


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of Tyrosinemia Type I.
  • Carrier testing in adults with a family history of Tyrosinemia Type I.


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations.

Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Please submit copies of diagnostic biochemical test results along with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
  • Amino Acid Analysis - Plasma (AA) and Organic Acids - Urine (OA) including succinylacetone and tyrosine metabolites.
  • Sequence analysis of the FAH gene is available and is required before deletion/duplication analysis.
  • Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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