Lowe syndrome

What else is it called?

  • Cerebrooculorenal syndrome
  • Lowe oculocerebrorenal syndrome
  • Oculocerebrorenal syndrome
  • Oculocerebrorenal syndrome of Lowe
  • Phosphatidylinositol-4,5-bisphosphate-5-phosphatase deficiency

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What causes it?

Lowe syndrome is an X-linked genetic disorder caused by a mutation in the OCRL gene that results in reduced activity of the phosphatidylinositol polyphosphate 5-phosphatase OCRL enzyme. This enzyme is involved in modifying fat molecules called phospholipids, with this condition the body is unable to modify phospholipids. About a third of affected males have a new mutation in the gene; in most of the rest, the disorder is inherited from a mother who is a genetic carrier of the condition.

How common is it?

Lowe syndrome is a rare genetic disorder that occurs almost exclusively in males. The prevalence is estimated to be between 1 and 10 males per 1,000,000 people. This condition has been reported in North and South America, Europe, Japan, and India.

What are the signs and symptoms?

Lowe syndrome predominantly affects the eyes, kidneys and the brain. Infants born with this condition usually have clouding of the lenses of both eyes [congenital cataracts] and other eye abnormalities which may affect your child’s vision. With only extreme cases would these require surgical removal.

It is estimated that half of the children who have this condition develop infantile glaucoma. Most children have a weak muscle tone from birth, behavioural problems and seizures have also been reported with this condition.

Kidney abnormalities such as Fanconi syndrome frequently develop in individuals with Lowe syndrome. The kidneys are involved in the uptake of certain salts and minerals and maintain levels within the body. With proximal tubular dysfunction of the Fanconi syndrome, the body cannot reabsorb nutrients. This may also lead to softening of bones and impact growth in the legs, potentially leading to hypophosphatemia rickets. Kidney problems that are carried into adult life can have serious implications on blood pressure and have the potential to be life threatening, leading to end stage renal disease.

How is it diagnosed?

Lowe syndrome is diagnosed when a reduced activity of the phosphatidylinositol polyphosphate 5-phosphatase OCRL enzyme is demonstrated in cultured skin cells [fibroblasts]. Molecular genetic testing for OCRL gene mutations is also available and accurately detects more than 95% of affected males.

Carrier testing for female relatives is available. Approximately 95% of carrier females older than 10 years of age have specific and distinctive abnormalities of the lens of the eye that can be diagnosed by an experienced ophthalmologist. Molecular genetic testing for carrier status is available if a specific OCRL gene mutation has been identified in a male relative. Biochemical testing for phosphatidylinositol polyphosphate 5-phosphatase OCRL enzyme activity is not reliable for carrier testing for Lowe syndrome because the range of enzyme activity spreads over the normal range.

Prenatal diagnosis is available with biochemical testing [enzyme assay] or molecular genetic testing if the OCRL gene mutation has been determined in an affected male relative or carrier mother.

Can it be treated?

Boys with Lowe syndrome should be monitored regularly for vision problems [especially later onset glaucoma], kidney function, growth, developmental progress, scoliosis, and joint problems, and dental problems. Treatment of Lowe syndrome usually requires a team of medical professionals including a paediatric ophthalmologist, nephrologist, geneticist, nutritionist, endocrinologist, neurologist, child development specialist, general surgeon, orthopaedist, and dentist. Low muscle tone [hypotonia] can sometimes result in feeding problems and may require tube feeding and standard measures for gastroesophageal reflux.

Proximal tubular dysfunction of the Fanconi type is treated with oral supplements of sodium and potassium bicarbonate or citrate. Doses must be determined on an individual basis. Oral phosphate and oral calcitriol are used to treat (or prevent) rickets. Bone density should be monitored periodically. Seizure disorders are treated with anticonvulsant medications. Behaviour problems are treated with behaviour modification and medications. End-stage renal disease has been treated successfully with dialysis and kidney transplantation in some late-adolescent adult men.

Do my family need to be tested?

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Most X-linked disorders affect males much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In some cases of Lowe syndrome, an affected male inherits the mutation from a mother who carries one altered copy of the OCRL gene. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family.

Females who carry one mutated copy of the OCRL gene do not have the characteristic features of Lowe syndrome. Most female carriers, however, have changes in the lens of the eye that can be observed with a thorough eye examination. These changes typically do not impair vision.

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: LAP070].

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