Lowe Syndrome - An Overview

Introduction

Lowe syndrome is an exceptionally rare condition affecting a gene located on the X chromosome that affects the eyes and leads to a change in vision. Lowe syndrome is also called oculocerebrorenal syndrome of Lowe. It is a multisystem disorder involving the eye, nervous system, and kidney. It has male predilection. The prevalence of the disease is approximately one in 50,000 in the general population. Lowe and colleagues first described Lowe syndrome in 1952.

What Are the Clinical Features Associated With Lowe Syndrome?

There is delayed development in patients suffering from Lowe syndrome, and the intellectual ability of the patients is moderate to severely compromised. It is also associated with behavioral changes and seizures. Weak muscle tone is present in individuals suffering from this disorder and is associated with feeding difficulties, problems with breathing, and delayed development of motor skills such as standing, sitting, and walking, and it also involves the gonads. Fanconi syndrome is associated with Lowe syndrome and affects the kidneys. It leads to increased urination and dehydration. In addition, there is an abnormal loss of certain substances such as organic acids, albumin, and protein. Glaucoma is associated with nearly 50 percent of the cases.

What Are the Causes of Lowe Syndrome?

• Lowe syndrome shows X-linked inheritance (affects genes located on the X chromosome) and affects males more than females.

• The major cause is a mutation in the OCRL (oculocerebrorenal syndrome protein) gene.

• Cells are the basic structural unit of any tissue. The cells are made up of a fatty substance known as membrane phospholipids that provide cellular integrity and also aid in the transport of vital substances such as proteins. This function is governed by the OCRL gene.

• A mutated OCRL gene results in an altered cellular framework, thereby, hindering the transport of proteins and other vital substances.

• OCRL gene mutation may affect various cell types, such as nerve cells, renal cells, and others.

What Are the Symptoms Associated With Lowe Syndrome?

1. Eyes - Congenital bilateral cataract (cloudy lens) is present in all patients. Glaucoma is present in 50 percent of patients in the early years of life and is occasionally seen later in life.

2. Nervous System - Severe hypotonia (decreased muscle tone ) is seen in Lowe syndrome patients with respiratory difficulty at an early age. Obsessive-compulsive disorder is seen with this syndrome. Severe episodes are seen in half of the patients. In some cases, febrile convulsions are also seen.

3. Renal - Fanconi syndrome is concomitant with Lowe syndrome, which worsens with age. Renal symptoms develop early in life and, if not treated, progress to end-stage renal failure.

How Is the Lowe Syndrome Diagnosed?

• Laboratory test indicates a reduced level of inositol polyphosphate-5-phosphatase activity.

• Genetic analysis is important to detect OCRL genes.

• For neurologic and musculoskeletal evaluation, electroencephalography (the test that measures electrical activity in the brain) or electromyography (a diagnostic test to assess the health of muscles) can be performed.

• Serologic tests should be done for Lowe disease to evaluate metabolic acidosis (a condition with too much acid in the body), reduced glomerular filtration rate, hypokalemia, vitamin D deficiency, and elevated creatinine phosphokinase and liver transaminases.

• Urine analysis will detect aminoaciduria and proteinuria.

What Is the Management of Lowe Syndrome?

Nervous System

• An interprofessional medical team is required that includes a pediatric ophthalmologist, nephrologist, geneticist, nutritionist, endocrinologist, neurologist, child development specialist, general surgeon, orthopedist, and dentist.

• Early targeted rehabilitation therapy treats hypotonia (decreased muscle tone) and its complications.

• Anticonvulsant drugs should treat seizures.

• Behavioral problems require psychological counseling.

• Drugs involve neuroleptics, and antidepressants such as tricyclic antidepressants can be given.

• Early intervention programs are recommended in early infancy, including physical therapy, occupational therapy, speech therapy, special education services, and services for the visually impaired.

Renal System

• Symptoms of Fanconi syndrome require early detection and treatment.

• Renal tubular acidosis is treated by alkali supplements such as sodium or potassium citrate and sodium bicarbonate.

• The end-stage renal disease requires renal dialysis and renal transplant.

• In case of polyuria, fluid supplements are given to the patients and can be given intravenous infusion.

Rickets

• Oral phosphates, calcitriol, and vitamin D supplements manage rickets.

• Bone density can be checked at regular intervals.

Eyes

• Surgery is done to remove cataracts, and it is recommended to promote optimum development of vision and management of the disease.

• Eyeglasses and contact lenses help to improve and correct vision.

• Glaucoma is treated with the help of eye drops. If conservative treatment does not work, surgery is done.

• Corneal keloids can occur, and surgery is done to remove them. However, there is no proven treatment to eradicate corneal keloids.

Musculoskeletal Complications

• Preventive treatments are required for musculoskeletal complications that maintain articular mobility to avoid contractures.

• The correct treatment of rickets should prevent osteopenia and pathological fractures.

• Standardized therapies such as surgery are required to prevent scoliosis (curvature in the spine).

• Because of low or decreased muscle tone, feeding problems are encountered, so a feeding tube is given.

What Is the Differential Diagnosis Associated With Lowe Syndrome?

• Congenital infections such as rubella (contagious viral infection characterized by a red rash). Abnormalities are present in the heart, ears, nerves, eyes, and ears, whereas Lowe syndrome mainly affects kidneys, nerves, and eyes and has no rash.

• Peroxisomal disorders (genetic metabolic disorders) are mainly characterized by decreased muscle tone, abnormal facial features, and mutation in different genes compared with Lowe syndrome.

• Muscle-Eye-Brain disease is a congenital disorder, and the genes responsible for this disorder differ from Lowe syndrome.

How to Prevent Lowe Syndrome?

Since Lowe syndrome is a genetic disorder, it is not preventable. However, there are certain measures that can be taken to manage the symptoms of the condition and prevent complications. These may include:

• Early Diagnosis: Early diagnosis of Lowe syndrome is essential to start early interventions and prevent or delay the onset of symptoms. Genetic testing is available for parents with a family history of the condition or for those who have had a child with Lowe syndrome.

• Regular Medical Checkups: Regular medical checkups can help monitor the progression of the disease and detect any potential complications early on.

• Genetic Counseling: Genetic counseling can help families understand the risks and inheritance patterns of Lowe syndrome and make informed decisions about family planning.

• Support and Resources: Connecting with support groups and resources can help families cope with the challenges of Lowe syndrome and access the latest information on research and treatments.

Conclusion

Lowe syndrome is a rare disorder characterized by multiple features and has increased prevalence in males. The syndrome has a variable prognosis, and early detection plays an important role in preventing fatalities that may be due to infections and renal and muscular ailments. Quality of life depends on the compromise of the nervous and renal systems, so early treatment is essential in treating the disorder.