Genetic liver disease

Early identification of underlying genetic cause to prevent organ damage

Identifying underlying genetic disorders plays an important role in the treatment and care of patients with liver disease. Appropriate use of screening tests in routine clinical practice can rule out possible causes of liver disease and assist in early identification and treatment of genetic liver diseases to prevent terminal organ damage.

Alpha-1-antitrypsin (A1A) deficiency

Why pay for the "gold standard" of phenotyping when it is only necessary 3% of the time?

To aid in the diagnosis of A1A deficiency, we have developed a state-of-the-art proteotype assessment that
detects disease-causing variants S and Z. When physicians begin by ordering our recommended proteotyping
test, they will receive a definitive answer 97% of the time. In the other 3%, where the mass spectrometry
proteotype and quantitative serum level are conflicting, phenotyping will automatically be ordered and performed.

Which test should I order?

Genetic testing to identify causative mutations may prove useful for patients suspected to have A1A deficiency, based on clinical findings or serum A1A levels, but that do not have evidence of the SZ or ZZ genotype by routine methods. Our testing performs full sequencing of the SERPINA1 coding region for the detection of rare null and non-S or non-Z disease-associated mutations.

A Test in Focus

David Murray, M.D., Ph.D., provides a brief overview of the Alpha-1-Antitrypsin Proteotype S/Z by LC-MS/MS, Serum test now available from Mayo Medical Laboratories. This test should be ordered for individuals suspected of A1A deficiency and can be used for diagnosis and identification of a specific proteotype to determine prognosis.


Once local lab testing has identified individuals with increased transerffin-iron saturation in serum and serum ferritin, molecular testing can be done to establish or confirm the diagnosis of hereditary hemochromatosis. Our HFE gene analysis test detects the two common disease-causing mutations: C282Y and H63D. The S65C mutation is reported only when it is observed as part of the C282Y/S65C genotype.

Wilson disease

Early diagnosis of Wilson disease allows for treatment and prevention of permanent organ damage. However, diagnosing WD can be challenging because its signs and symptoms are often hard to distinguish from those of other liver diseases, such as hepatitis. To aid clinicians, our algorithmic approach to testing ensures the right test is performed at the right time.

First-tier screening

A variety of laboratory tests are recommended in the initial evaluation for Wilson disease, but in approximately 95% of cases, serum ceruloplasmin is below normal.

Copper tissue testing available, when necessary

Liver biopsy can be useful to help interpret discrepant biochemical or molecular results. Our Metals Laboratory has more than 30 years of clinical experience and a staff of 30 full-time employees.

Genetic testing to confirm diagnosis and identify at-risk family members

After initial testing, diagnosis can be confirmed through analysis of the ATP7B gene. Additionally, a confirmed genetic diagnosis enables the screening of siblings who may be able to start treatment before symptoms

Lysosomal acid lipase deficiency (LAL-D)

Late-onset LAL-D is likely underdiagnosed and frequently identified after liver pathology reveals findings similar to NAFLD or NASH. Early diagnosis of LAL-D is critical to stopping the progression of the disease, as studies have shown that nearly 50% of pediatric and adult LAL-D patients progress to fibrosis, cirrhosis, or liver transplantation within three years of first clinical manifestation.

New guidelines recommend LAL-D be ruled out when evaluating children
and adults for NAFLD

2017 NASPGHAN guidelines: Differential diagnosis for NAFLD in children

2017 AASLD guidelines: Differential diagnosis for NAFLD in adults

Learn more about how to order these evaluations at your institution.