About Lowe Syndrome
Lowe Syndrome (LS) is a rare genetic condition that causes physical and mental handicaps, and medical problems. It was first described in 1952 by Drs. Lowe, Terrey, and MacLachlan at the Massachusetts General Hospital in Boston. 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.
The condition became known as "Lowe syndrome" named after Dr. Charles Lowe, the senior member of the group that described it. Because of the three major organ systems involved (eyes, brain, and kidney), it is also known as OCRL (oculo-cerebro-renal) syndrome. Much research has taken place in the last few years. The gene has been mapped and the deficient enzyme has been identified, although its role is not fully understood. 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 the genetics involved
Lowe syndrome virtually always presents only in males, however exceptionally rare cases have been documented in females. Individuals with Lowe Syndrome are born with cataracts in both eyes, which are usually removed at a few months of age. Most are fitted with glasses, contacts, or a combination of the two. Glaucoma is present in about 50% of Lowe syndrome cases, though usually not at birth. Prescription eye drop and/or surgery is required to maintain appropriate eye pressure in these cases
While not present at birth, many Lowe Syndrome
individuals develop kidney problems at approximately
one year of age. This is characterized by the
abnormal loss of certain substances into the urine,
including bicarbonate, sodium, potassium, amino
acids, organic acids, albumin and other small
proteins, calcium, phosphate, glucose, and
L-carnitine. This problem is known as Fanconi-type
renal tubular dysfunction and can also be seen in
certain other diseases and syndromes. In Lowe
syndrome, the Fanconi syndrome may be mild and
involve only a few substances or may be severe and
involve large losses of many substances. Medications
can be prescribed to replace the lost substances.
Recently the discovery of a common genetic basis for Lowe Syndrome and Dents disease has blurred the distinction between the two diseases. Please see the Dents section on this website.
Lowe Syndrome Diagnosis
Lowe syndrome is caused by a low activity of the enzyme inositol polyphosphate 5-phosphatase OCRL-1, which is encoded by the OCRL gene (chromosomal locus Xq26.1). Diagnosis may be confirmed by DNA tests or cultured skin fibroblasts demonstrating reduced (<10% of normal) activity of the enzyme.
The syndrome is caused by a DNA mutation - a single defective gene on the X-chromosome - that results in the lack of an enzyme. The mutation can occur without any family history (a spontaneous mutation) or may be inherited through the mother. Babies are born with bi-lateral cataracts, hypotomia (muscle weakness), kidney problems (wasting of essential nutrients) impaired growth, intellectual impairment and later may suffer brittle bones, arthritis, rickets, epilepsy (seizures) and behavior problems (autistic spectrum disorder). Many also have cysts and dental problems.
Children may be discovered to have fractures without the parents or carers realising. As for many Lowe ailments, dental problems are often only apparent to a pediatric specialist having the patience, time and ability to closely examine the children despite thier behaviour problems. Also See Caring for Lowe Children's Teeth.
The diagnosis may be confirmed by testing for reduced levels of the OCRL enzyme in cultured skin fibroblasts or by a DNA test using a blood sample. As some DNA tests may not identify a mutation an enzyme test is the only conclusive test.
See Baylor diagnostic flow chart and 2004 article by Great Ormond Street Hospital UK. entitled "Early proximal tubular dysfunction in Lowe's syndrome" Laube GF, Russell-Eggitt IM, van't Hoff WG. Institute of Child Health and Great Ormond Street Hospital for Children, London, UK. The early diagnosis of Lowe's syndrome can be difficult. Urinary excretion of retinol binding protein (RBP) and the lysosomal enzyme N-acetyl-glucosaminidase (NAG) were significantly increased in boys with Lowe's syndrome. Measurement of these urine parameters is recommended in suspected cases.
Symptoms vary widely. Some boys are mildly affected and able to attend normal schools with special needs help, while others are severely affected with loss of sight and mobility. The medical and behaviour problems may require respite care or full-time residential care. The NHS approach is of separate treatments of each clinical symptom, and family support by the local authorities through a special educational needs assessment (SEN). The "challenging behaviour" means that they frequently need to be handled in a playful manner, to prevent them from mischief. Parents, carers, teachers etc may need to be aware of UK laws on what is acceptable contact and on physical restraint.
UK DNA testing for Lowe Syndrome may be requested from Dr A Wallace Email: awallace @ smh5.cmht.nwest.nhs.uk St Mary's Hospital Regional Genetics Services, Hathersage Road, Manchester M13 0JH.
DNA and Biochemical tests and pre-natal testing is offered by Baylor College of Medicine USA.
The following is one parents description of the syndrome: Boys are born with cataracts in both eyes and hypotomia (muscle weakness/floppy baby syndrome) and failure to thrive. The cataracts are usually removed at a few months old and the baby fitted with glasses and later contact lenses. Glaucoma occurs in some cases when older. Due to the weak muscles, there may be feeding (needing tube feeding) and digestion problems, and delayed development with crawling, standing and walking. Some parents say Growth Hormone greatly improved muscle development.
After a year old, most boys develop kidney problems, with abnormal loss of substances in the urine, including bicarbonate, sodium, potassium, amino and organic acids, calcium, phosphate and L-carnitine. This is known as Fanconi-type renal tubular dysfunction. The losses may be mild to severe with large losses of many substances. Blood and urine tests are needed to establish the pH acidity and prescriptions needed to replace the lost substances. The kidney problems may also cause kidney stones and may be a factor for poor growth and small stature common with Lowe syndrome. Although not causing any medical problems, clusters of small cysts may become apparent on the skin around the sides of the waist. Cysts may also be shown by MRI scans to be present in the Brain.
Lowe Boys have mild to severe mental impairment,
delayed development and behaviour characterised as a
autistic spectrum disorder .The behaviour includes
temper tantrums, attention deficit disorder and obessive
behaviour. The degree of mental and behaviour
impairment varies widely and does not seem to be related
to the severity of the physical symptoms. Most children
can speak and hold a conversation (by 5 -10 years old),
read and even play computer games.
The boys have affectionate, happy and excited personalities with a cheeky sense of humor. When excited by a favorite subject many boys jump up and down with hand flapping and have obsessive behaviour with certain subjects such as videos or switches. Parents suffer from behaviour problems including stubbornness and severe temper tantrums (the famous Lowe Tantrum!) with periods of hyperactivity with inability to cooperate or control impulses. My son is aware of his behaviour and although unable to control it, will say sorry afterwards. Some also suffer from epileptic siezures that may become frequent and severe.