Introduction
Lowe syndrome is associated with cataracts at birth, kidney issues that typically appear in the first year of life, and brain abnormalities linked to intellectual difficulties. Lowe syndrome is an X-linked genetic disorder that is inherited. Many people with Lowe syndrome experience delayed development, and their intellectual capacity can range from average to seriously diminished. Children with this illness have also been noted to experience behavioral issues and seizures. Neonatal hypotonia, a condition in which most affected children are born with poor muscle tone, can cause respiratory issues, feeding issues, and a delay in developing motor abilities, including sitting, standing, and walking. Other names for Lowe syndrome are
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Oculocerebral syndrome of Lowe (OCRL).
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Oculocerebral syndrome.
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Phosphatidylinositol-4,5-bisphosphate-5-phosphatase deficiency.
What Are the Causes of Lowe Syndrome?
The OCRL gene is mutated in Lowe syndrome. The membrane phospholipid family of fat (lipid) molecules is modified by an enzyme produced by the OCRL gene. The OCRL enzyme helps manage the movement of some chemicals into and out of the cell membrane by regulating the amounts of particular membrane phospholipids. The actin cytoskeleton, a web of fibers that forms the cell's structural framework, is partially regulated by this enzyme. The actin cytoskeleton performs various vital tasks, including regulating cell shape and enabling movement. Certain OCRL gene mutations stop the OCRL enzyme from ever being produced. Some mutations cause the enzyme's activity to decrease or disappear entirely or stop it from interacting with other proteins inside the cell. The mechanism through which OCRL mutations result in the distinctive traits of Lowe syndrome is currently under investigation. It is unclear why the medical issues connected with this illness are primarily restricted to the brain, kidneys, and eyes when the OCRL enzyme is present throughout the body. Other enzymes can make up for the faulty OCRL enzyme in undamaged tissues.
How Is Lowe Syndrome Inherited?
This disorder has an X-linked pattern of inheritance. If the defective gene that causes a disorder is found on the X chromosome, one of the two sex chromosomes, the ailment is said to be X-linked. One mutated copy of the gene per cell is enough to induce the disease in males (who have only one X chromosome). A mutation must exist in both copies of the gene in females (who have two X chromosomes) for it to result in the condition. Males are typically affected by most X-linked illnesses substantially more often than females. Fathers cannot pass on X-linked qualities to their sons, a trait of X-linked inheritance. In some instances of Lowe syndrome, the mutated OCRL gene is inherited by the mother of the sick male. Some cases are caused by novel gene mutations and affect boys who have no family history of the condition. Lowe syndrome symptoms are absent in females with one mutant copy of the OCRL gene. Nonetheless, a thorough eye examination can reveal alterations in the eye's lens in most female carriers. Usually, these alterations do not impede eyesight.
What Are the Symptoms of Lowe Syndrome?
The signs and symptoms of Lowe syndrome include:
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Cataracts are present at birth in both eyes.
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Glaucoma (a condition where elevated pressure in the eye damages the optic nerve and may even lead to blindness).
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Hypotonia (abnormally low muscle tone) may present at birth.
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Behavioral problems.
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Keloids (abnormal growth in the cornea) may present in one or both eyes.
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Seizures.
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Kidney issues like proximal tubular dysfunction of Fanconi type result in the loss of some chemicals (such as phosphates, bicarbonates, and amino acids) into the urine that is usually filtered before excretion or reabsorbed by the body.
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Short stature.
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Dental cysts and abnormal dentin formation.
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Scoliosis (a condition where the spine is curved sideways).
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Vitamin D deficiency results in soft bones that are more prone to fracture.
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Rickets (a condition where the bones become soft and weak).
Following surgery, some patients have had a delayed bleeding diathesis defined by normal hemostasis and clot formation, which is then abruptly followed by bleeding a few hours later. This may be a crucial factor to consider with any operation, particularly with cataracts and glaucoma surgeries where internal bleeding could have significant consequences.
How Is Lowe Syndrome Diagnosed?
The different diagnostic modalities of Lowe syndrome are:
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Skin Fibroblast Culture: Reduced inositol polyphosphate-6-phosphate activity of OCRL-1.
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Electroencephalography: This test will be done for neurologic findings.
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Electromyography: They are suggested to check musculoskeletal findings.
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Serologic Testing: Metabolic acidosis (this condition arises when excess acid production in the body), reduced GFR (glomerular filtration rate), hypokalemia (low potassium level in blood), vitamin-D deficiency, and increased liver transaminases and CPK (creatine phosphokinase).
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Urinalysis: Aminoaciduria (presence of amino acids in urine) and proteinuria (presence of proteins in the urine) are determined by undergoing this test.
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Molecular Genetic Testing or Enzyme Assay - This test is done to detect OCRL gene mutation.
How Is Lowe Syndrome Managed?
A medical team of pediatric ophthalmologists, nephrologists, geneticists, nutritionists, endocrinologists, neurologists, child development experts, general surgeons, orthopedists, and dentists is typically needed to treat Lowe syndrome.
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Hypotonia, or Low Muscle Tone: They can occasionally cause eating issues that may necessitate tube feeding and conventional treatments for acid reflux.
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Cataract: To ensure optimal eyesight development, early cataract removal is advised. Both contact lenses and spectacles help correct eyesight.
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Glaucoma: Half of all males have glaucoma, which can occasionally be treated with eye drops, but surgery is frequently necessary and not always successful.
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Keloids: Although surgical removal of corneal keloids is occasionally possible, they typically recur more violently than before. A trustworthy treatment cannot consistently remove corneal keloids.
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Proximal Tubular Dysfunction: Oral Sodium and Potassium bicarbonate or citrate supplementation treat proximal tubular dysfunction of the Fanconi type. Doses must be established individually.
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Rickets: Oral phosphate and Calcitriol are prescribed to cure (or prevent) rickets. Periodically checking on bone density is recommended.
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Anticonvulsant Drugs: They are used to treat seizure disorders.
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Medication and Behavior Modification: This method is used to address behavioral issues.
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Early Intervention Programs: Physical therapy, occupational therapy, speech and language therapy, special education services, and assistance for visually impaired children should all be included in early intervention programs. These programs should start in the first few months of life.
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Others: Boys with Lowe syndrome need regular checks for renal function, scoliosis, joint issues, eye issues (particularly later-onset glaucoma), growth, developmental progress, and dental issues. In some late-adolescent adult men, end-stage renal illness has been successfully managed with dialysis (a process of removing waste and excess fluid build-up from the blood when the kidney fails to function properly) and kidney transplantation.
Conclusion
The outcome varies, and early diagnosis is essential to avoid potentially fatal complications brought on by renal disease, hypotonia, or infection. Importantly, the degree of neurological and renal deterioration significantly impacts the quality of life. Visual acuity is rarely better than 20/100 and is greatly influenced by the severity and course of amblyopia (one eye's impaired vision due to early abnormal visual development) and glaucoma complications. However, the lifespan of the affected person can be improved by treating the associated symptoms.
