Sequencing.com — Outsmart Your Genes
Knowledge CenterDNA EducationBlog

AGK-Related Disorders: Sengers Syndrome & Cataract 38

Medically reviewed by Brandon Colby, MD, last reviewed

AGK-related disorders and Sengers syndrome

AGK-related disorders are rare inherited conditions caused by variants in the AGK gene. Some cause cataracts present at birth without affecting other parts of the body, while Sengers syndrome also affects the heart and muscles. This article explains what the AGK gene does, how these conditions are inherited, and how genetic testing fits into diagnosis.

What the AGK Gene Does

The AGK gene provides instructions for making a protein that works in mitochondria, the parts of cells that produce energy.

This protein has two main jobs:

  • It helps make fats that cells use to build their membranes and send signals.
  • It helps place proteins in the inner membrane of mitochondria. These proteins move substances needed for energy production.

When the AGK protein is missing or does not work properly, cells may have trouble producing the energy they need. Problems with either job may contribute to AGK-related disease.

Conditions Linked to the AGK Gene

  • Sengers syndrome: The main AGK-related disorder. This mitochondrial condition was first described in 1975 and linked to the AGK gene in 2012. Key features include cataracts present at birth or in the first weeks of life, hypertrophic cardiomyopathy (thickening of the heart muscle), muscle weakness, exercise intolerance and lactic acidosis (a buildup of lactic acid in the blood).
  • Cataract 38, autosomal recessive: AGK variants have been reported in one family with cataracts present from birth and no heart or muscle involvement.

The severity of Sengers syndrome varies. In some infants, cardiomyopathy and lactic acidosis appear early and can be life-threatening. Others have a milder course and live into adulthood. A 2014 study reviewed the features seen in 29 patients and described this range.

Researchers have also reported a form of Sengers syndrome associated with a disease-causing variant in both copies of TIMM29. This finding suggests that a Sengers-like clinical picture is not always caused by variants in AGK.

How AGK-Related Disorders Are Inherited

Both conditions, Sengers syndrome and Cataract 38, follow an autosomal recessive pattern. A person may be affected when both copies of the AGK gene carry a disease-causing variant, one inherited from each parent. Parents who each carry one variant are typically healthy carriers. When both parents are carriers, each pregnancy has a 25% chance of an affected child, a 50% chance of a child who is a carrier and a 25% chance of a child who inherits neither variant.

Diagnosing AGK-Related Disorders

Doctors may suspect Sengers syndrome when an infant has congenital cataracts together with a thickened heart muscle, low muscle tone or high lactic acid levels. Evaluation may include an eye exam, an echocardiogram, blood lactate testing and sometimes a muscle biopsy. Finding disease-causing variants in both copies of the AGK gene supports the diagnosis, which a physician makes alongside the clinical findings.

Because cataracts often appear first, a child may initially be tested only for genes linked to isolated cataracts. Some AGK changes are also larger deletions that standard sequencing analysis can miss. A 2026 case report described a child with Sengers syndrome who was first thought to have isolated cataracts until copy number analysis found an AGK deletion.

How Genetic Testing Can Help

  • Supporting a diagnosis: Identifying AGK variants, together with clinical findings, can help a physician confirm Sengers syndrome and give families a clearer explanation for their child's symptoms.
  • Planning care: There is currently no cure or variant-specific treatment for Sengers syndrome. A confirmed diagnosis helps the care team plan early cataract surgery, regular heart monitoring and management of cardiomyopathy and lactic acidosis.
  • Family planning: Once the variants in a family are known, relatives can be tested to learn whether they are carriers, and couples can discuss reproductive options with a genetic counselor.

Living with a rare condition like Sengers syndrome, or waiting for answers about a child's health, can feel overwhelming. A confirmed genetic diagnosis can help families and care teams plan monitoring, connect with the right specialists and understand the chances for future pregnancies. If you have questions about AGK-related disorders or a test result, your physician or a genetic counselor is the best place to start.

Resources

These organizations and resources are provided for education and support. They are not endorsements or medical advice.