Historically, the diagnosis of Lowe syndrome in a potentially affected male was usually made by a geneticist (a physician specifically trained in genetics). In many cases, however, there are a few initial clues (symptoms) to assist in diagnosis. For example, you may see low muscle tone, cataracts, infantile glaucoma, undescended testes, or a sacral dimple. A number of the clues (symptoms) of Lowe syndrome may not manifest themselves until a later age.

Today we have a number of highly accurate diagnostic techniques available. This page will help you understand those techniques and when they are applicable. We will discuss the methods for both post-natal and pre-natal situations.

The Genetics Behind Lowe Syndrome

LS is caused by a single defective gene (an alteration or “mutation”) in a gene called OCRL1. Because of this defective gene, an essential enzyme called PIP2-5-phosphatase is not produced. This is the underlying cause of Lowe syndrome.

This enzyme is essential to normal metabolic processes that take place in a part of the cell called the Golgi apparatus. Because of the enzyme deficiency, cell functions regulated by the Golgi are abnormal, leading to many of the effects of Lowe syndrome, including cataracts and kidney and brain problems. The gene has been mapped and the missing enzyme identified, but exactly how the deficiency leads to these effects is not yet fully understood.

The gene responsible for Lowe syndrome was identified in 1992, and in 1995 researchers discovered that the gene defect causes the enzyme deficiency. Researchers continue to investigate the function of the gene and the complex biochemistry and cellular mechanisms of Lowe syndrome, as well as areas such as behavior and clinical care.

In rare cases, Lowe syndrome can also occur in females. Learn how this happens.

Because the OCRL1 gene and the PIP2-5-phosphatase enzyme are what testing looks for, both DNA and enzyme-based diagnostic methods below are built on this genetic cause.

Learn More

For a detailed medical description of Lowe syndrome, visit GeneReviews. Clinicians and researchers can find additional references on our For Healthcare Providers page.

How Lowe Syndrome is Diagnosed

The actual method(s) used to diagnose Lowe syndrome will depend on whether it is a pre-natal or post-natal situation. The following sections provide more information on the available diagnostic techniques for both post-natal and pre-natal situations.

Testing After Birth (Post-Natal)

    Since clinical diagnosis is not considered accurate by itself, it is usually used as a precursor to one of the scientific diagnostic methods available today (Enzyme or DNA analysis).

    In clinical diagnosis, the known symptoms of Lowe syndrome are compared to those of an affected male. Family history is also carefully examined, usually with the aid of a genetic counselor. Assuming there is a reasonable suspicion of Lowe syndrome, the child’s mother can be examined by a trained ophthalmologist for the tell-tale “snowflake” lenticular opacities.

    Scientific research has shown that the X-linked gene mutation that causes Lowe syndrome leads to a deficiency in the production of a certain enzyme (phosphatidylinositol-4, 5-bisphosphate phosphatase).

    We can look at the level of this enzyme in a potentially affected male to confirm Lowe syndrome diagnosis. The enzyme test is done by obtaining a small skin sample, which is cultured and sent to one of the available testing laboratories.

    Through research, we understand where the defective gene (called OCRL1) is located, and also the specific job it has relating to enzyme production. We are able to perform DNA analysis on a potentially affected male to prove a diagnosis of Lowe syndrome with approximately a 99% accuracy.

    DNA analysis can also be used to test for the Lowe syndrome mutation in potential female carriers.

    Testing Before Birth (Pre-Natal)

      Scientific research has shown that the X-linked gene mutation that causes Lowe syndrome leads to a deficiency in the production of a certain enzyme (phosphatidylinositol-4, 5-bisphosphate phosphatase).

      Provided the actual gene mutation is known, DNA Analysis can be used effectively for pre-natal diagnosis.

      Ultrasound examination of the unborn fetus to determine the existence of cataracts. This technique is most useful in situations where there is a strong family history of Lowe syndrome.

      Flowcharts

      These flowcharts illustrate the general steps taken to confirm a diagnosis of Lowe syndrome.

      Post-Natal Diagnosis
      Pre-Natal Diagnosis

      Where to Get Tested

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