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, a number of the symptoms of Lowe Syndrome may not manifest themselves until a later age.
Today we have a number of highly accurate diagnostic techniques available. The section will help you understand those techniques and when they are applicable. We will discuss the methods for both post-natal and pre-natal situations. For example, you may see low muscle tone, cataracts, infantile glaucoma, undescended testes, sacral dimple. A number of the clues (symptoms) of lowe syndrome may not manifest themselves until a later age.
A very detailed medical description of Lowe Syndrome can be found on GeneReviews. This article is suggested for medical professionals and researchers who need to learn more about Lowe Syndrome, including the technical details of diagnosis and the genetics involved with Lowe Syndrome.Go to Article
The actual method(s) used to diagnose Lowe Syndrome will depend on whether it is 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.
Since clinical diagnosis is not considered accurate by itself, it is usually used as pre-cursor 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 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 (visit the Carrier Detection section and go to the opthalmologic examination sub-section).
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.
The following diagnostic techniques are available for diagnosing a male who may be affected by Lowe Syndrome. The flowchart illustrates the general steps taken to confirm a diagnosis of Lowe Syndrome.
The following diagnostic techniques are available in pre-natal situations. The flowchart illustrates the general steps taken to confirm a diagnosis of Lowe Syndrome in a fetus.
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.
Due to the extensive medical research on Lowe Syndrome in the last decade, a reliable biochemical diagnostic test is now available. What makes this test possible is the discovery of the deficient enzyme in 1995 by Dr. Robert Nussbaum and his colleagues at the National Institutes of Health (NIH). The missing enzyme is called phosphatidylinositol 4,5-biphosphate 5 phosphatase.
The test is done by obtaining a small skin sample, usually in the child’s local community. Over several weeks, a fibroblast cell culture is grown using the skin sample. This culture is sent to one of the available testing laboratories, such as the Biochemical Genetics Laboratory at Baylor College of Medicine in Houston, Texas, where it usually takes a few weeks to obtain the results.
Costs involved include physician’s fees for taking the skin sample, the cost for establishing the initial culture, shipping costs, and the cost of analysis at the Baylor lab. Currently, the cost of the lab analysis is $320. Many insurance programs will cover most of these costs. Parents and their physicians who are interested in making arrangements to have the test done should contact Dr. O’Brien.
The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex. Am J Hum Genet. 1995 Oct;57(4):817-23.
Lowe Syndrome, a deficiency of phosphatidylinositol 4,5-biophosphate 4-phosphatase in the Golgi apparatus. Hum Mol Genet. 1995 Dec;4(12):2245-50.
The following table is a listing of laboratories that provide DNA and/or biochemical tests for Lowe Syndrome.
Rifaat Rawashdeh, MS, MSc
Phone: (404) 778-8523
Fax: (404) 778-8559
Alice Tanner, PhD, MS, CGC
Phone: (404) 778-8469
Contact: Sharon F Suchy, PhD, FACMG
Phone: (301) 519-2100 ext 6139
Fax: (301) 519-2892
Genetic Counselor: María Garcia-Hoyos, PhD
Phone: (+34) 963212340
Fax: (+34) 963212341
Contact: Anne Quaschner
Genetic Counselor: Dr Uta Goelnitz, PhD
Phone: (+49) (0)381-20 36 52 16
Fax: (+49) (0)381-20 36 52 19
Contact: Mato Nagel, MD
Phone: (+49) 3576287822
Fax: (+49) 3576387944
Contact: Dr Hagen Pommerenke, PhD
Phone: (+49) 381-7022750
Fax: (+49) 381-7022759
Contact: Nicole Monnier, PhD
Phone: (+33) 476765573
Fax: (+33) 476765837
Contact: Joel L Lunardi, PhD
Phone: (+33) 476765573
Fax: (+33) 476765837