Oculocerebrorenal Dystrophy (Lowe Syndrome) 

Updated: Apr 24, 2018
Author: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG 

Overview

Background

In 1952, Lowe and colleagues described an infant with congenital cataracts and mental retardation. When more patients were described, the phenotype was expanded to include the renal tubular defects that comprise Fanconi syndrome, and an X-linked inheritance pattern was noted. In 1992, Nussbaum and colleagues reported that mutations of OCRL1 caused the rare X-linked disorder oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, which includes the diagnostic triad of congenital cataracts, neonatal or infantile hypotonia with subsequent mental impairment, and renal tubular dysfunction.

Pathophysiology

Lowe syndrome is caused by an inherited mutation in the OCRL gene, mapped to chromosome Xq 26.1, which encodes the OCRL1 protein. The OCRL1 protein is an inositol polyphosphate 5-phosphatase primarily located in the trans- Golgi network (TGN), on endosomes, and at the endocytic clathrin coated pits. It can also translocate to plasma membrane ruffles upon stimulation with growth-factors.

The main substrates for Lowe syndrome are two phosphoinositides (Ptdln): PtdIn4,5P2 and PtdIn3,4,5P3. OCRL1 has been localized to the trans -Golgi network and various compartments of the endocytic pathway (traffic), where it is found in the clathrin-coated pits, clathrin-coated vesicles, variable functioning endosomes (early, signaling, recycling), and the basal body of primary cilia. Therefore, OCRL1 affects several cellular processes, namely membrane trafficking, actin cytoskeleton remodeling, cell migration, cell polarity, and phagocytosis. Cytokine defects have also been reported in mammalian cell lines lacking OCRL1 attributed to dysregulation of actin assembly.

In addition, OCRL1 plays an important role in ciliogenesis by modulating trafficking of ciliary components into the cilium, presumably through binding with Rab8. Studies in zebrafish demonstrated defects in cell migration, cell spreading, and primary cilia assembly in the presence of mutant OCRL1.[1] These studies provide strength to the classification of Lowe syndrome as part of the ciliopathy-associated diseases.

For a more thorough review of the role of phosphatidylinositol and the cellular and physiological functions of OCRL1 please refer to the following 2 reviews: (1) McCrea HJ, De Camilli P. Mutations in phosphoinositide metabolizing enzymes and human disease. Physiology (Bethesda). Feb 2009;24:8-16[2] and (2) Mehta ZB, Pietka G, Lowe M. The cellular and physiological functions of the Lowe syndrome protein OCRL1. Traffic. May 2014;15(5):471-87.[3]

Membrane trafficking defects caused by mutation in OCRL may explain renal tubular defects observed in Lowe syndrome, including the inability of proximal tubular cells (PTC) to reabsorb low-molecular weight (LMW) proteins and other solutes such as phosphorus and bicarbonate from the glomerular filtrate. The absorption of LMW proteins occurs in the PTC through clathrin-mediated endocytosis via 2 multiligand receptors (megalin and cubilin) present in the PTC apical border.

Megalin is internalized by endocytosis and delivered to vacuolar endosomes, which then sort megalin into recycling tubules and deliver it back to the plasma membrane, thus keeping an abundant number of megalin receptors at the apical surface of PTC for further endocytosis and recycling. In OCRL1 deficiency, megalin trafficking and recycling by the endosome is impaired, leading to accumulation of megalin in the endosome. The low number of megalin at the PTC apical border explains the reduced endocytosis of low-molecular weight proteins that occur in Lowe syndrome.[3] Proteomic analysis of urine from patients with Lowe syndrome typically show low levels of megalin and cubilin denoting a decrease in the number of these multiligand receptors in the PTC.[4]

The OCRL gene is located on Xq25-q26 and consists of 24 exons occupying 52kb. Sequence analysis detects mutations in 95% of males and 95% of female carriers. Several mutations in the OCRL gene have been described, including truncation mutations, missense mutations, and large deletions. New mutations do occur in about 32% of cases, and germline mosaicism is not uncommon. For more detailed genetic information, please refer to the Online Mendelian Inheritance in Man website catalog (OMIM).

Recently, mutations in the OCRL gene have also been identified with renal tubular reabsorption defects in a subset of patients with another X-linked disease called Dent-2 disease, characterized by LMW proteinuria, hypercalciuria, and nephrocalcinosis.[5, 6] Classic Dent disease (also called Dent-1 disease) typically does not include renal tubular acidosis or extra renal manifestations. It occurs due to a mutation in the CLCN5 gene located in Xp11.22 and encodes the chloride channel 5 (ClC-5). These CIC-5 channels are predominantly expressed in the proximal tubule and in the intercalated cells of the distal nephron.

Patients with Dent-2 disease can be easily differentiated from patients with Lowe syndrome based on their lack of major extra-renal manifestations such as cataracts and hypotonia. However, mildly elevated serum muscle enzyme levels, mild cognitive or behavioral impairment, growth retardation, and cryptorchidism have been reported in Dent-2 disease. Lowe syndrome and Dent-2 disease both share defective endocytic trafficking due to loss of OCRL1 function; therefore, cells that are highly polarized with a high rate of endocytosis, such as PTC, lens epithelium, and neurons, are expected to be more sensitive to the effects of OCRL1 nonfunctions.

However, despite recent advances in molecular genetics, the exact mechanism by which the mutations in OCRL gene causes the phenotypic characteristics of Lowe syndrome or the limited renal manifestations of Dent-2 disease remains poorly understood. Among possible theories for this phenotypic variability include presence of modifier loci in the gen and epigenetic factors.

Epidemiology

Frequency

International

Lowe syndrome is an uncommon, panethnic disorder with the prevalence of 1:200,000-1:500,000 births. In the United States, as of the year 2000, 190 living affected males were known to the Lowe Syndrome Association (LSA), which estimates this number to represent approximately 50% of all cases.

Mortality/Morbidity

The high mortality rate observed in the first few months of life is attributed to the severe metabolic derangements associated with Fanconi syndrome. These patients are predisposed to failure to thrive, severe metabolic acidosis, electrolyte imbalances, and dehydration. Patients with Lowe syndrome also have a tendency to develop pneumonia due to hypotonia and poor cough reflex. Other causes of death include infection and status epilepticus. Sudden unexplained death can also occur. Death usually occurs in the second or third decade of life. A few patients with Lowe syndrome are reported to have survived into the fourth and fifth decades of life with chronic kidney failure.

Sex

Lowe syndrome is inherited in an X-linked fashion. Thus, the vast majority of patients are males. Few cases have been reported in females. Most affected females have X-autosomal translocations involving the OCRL1 locus, which permits full expression of the Lowe syndrome phenotype.

Age

Although the diagnosis is not always straightforward, virtually all patients have some degree of hypotonia with the absence of deep tendon reflexes and cataracts present at birth. Other nervous system manifestations and mental retardation become obvious later. Renal tubular function may essentially be normal at birth, but the typical abnormalities often are detectable by age 1 year. Serum creatinine levels remain normal, with normal urinary creatinine clearance during the first decade of life. Chronic kidney disease with an increase in the serum creatinine levels develops slowly, starting in the second decade of life in some patients.

Prognosis

In childhood, death may occur as a result of renal dysfunction with electrolyte problems, hypotonia, seizures, infections (respiratory or enteric), or sudden death while sleeping.

Death in patients with Lowe syndrome that occurs between the second to fourth decades of life is usually due to progressive renal failure. The decision to initiate dialysis in patients with Lowe syndrome is medically and ethically complex and depends on the degree of mental retardation, the medical condition of patient, quality of life, and family and social system support. Successful dialysis and renal transplantation has been reported in few adult patients with Lowe syndrome.

Patient Education

Education is directed toward self-help skills and must be tailored to meet the individual strengths and weakness of each patient. Physical therapy should focus on encouraging walking and preventing secondary effects of hypotonia. Occupational therapy is directed toward personal hygiene. Behavioral difficulties may interfere with education, and specialized plans may be necessary to deal with these difficulties and maximize the child's learning.

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education article Cataracts.

The Lowe Syndrome Association website http://www.lowesyndrome.org/ is an excellent resource for information and support to families of children with Lowe syndrome.

 

Presentation

History

Oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, is most often diagnosed at birth or in early infancy based on physical characteristics; therefore, history does not usually contribute to the diagnosis. However, a careful review of history is important in documenting disease manifestations, especially neurological and behavioral abnormalities. Obtaining a detailed family history is essential in order to identify any potentially affected male relatives on the maternal side or potential maternal carrier status.

Intelligence

Although about 10% of boys with Lowe syndrome have intelligence within the low-normal to borderline ranges (intelligence quotient [IQ] of 70 and above), most have more significant intellectual impairment.

About one third of patients have profound mental retardation, but most have IQs that fall within the moderate range of 40-54. About 25% of patients have an IQ greater than 70.

Socioeconomic status, maternal IQ, OCRL1 mutation, and MRI findings do not correlate with intellectual outcome; thus, prediction of intellectual outcome at birth is not possible. Intelligence is stable over the person's life span.

Seizures

Seizures occur in about one half of all patients with Lowe syndrome and typically appear in children younger than 6 years. Seizure types vary widely and include myoclonic seizures, generalized tonic-clonic seizures, infantile spasms, partial complex seizures, and atonic seizures.

Febrile seizures are more common in persons with Lowe syndrome than in the general population (9% vs 1%).

Behavior

Although most patients with Lowe syndrome are friendly and sociable, a characteristic pattern of behavioral difficulties is common.

Abnormal behavior may include temper tantrums, aggression, unusual repetitive movements, irritability, and rigidity.

Individuals may also have unusual preoccupations or obsessions, and self-injurious behavior is not uncommon.

GI problems

Constipation is common and may be quite severe; severity typically decreases with age.

Renal

Renal dysfunction is not commonly evident at birth but rather noted during the first weeks or months of life and is typically a slowly progressive chronic renal failure that results in end-stage renal disease in the second or third decade of life.

Physical

The typical facial appearance of patients with Lowe syndrome consists of deep-set small eyes, frontal bossing, and an elongated face.

Ophthalmologic examination

Cataracts are a hallmark of Lowe syndrome and are always present at birth. Pathologic changes in the ocular lens occur prenatally and have been described in fetuses with Lowe syndrome at 20 weeks' gestation and 24 weeks' gestation.

Glaucoma, with or without buphthalmos, occurs in about 50-60% of boys with Lowe syndrome and is usually bilateral. Glaucoma is typically diagnosed in the first year of life but may present at any age.

Keloids may spontaneously form over the cornea or the conjunctiva in one or both eyes without preceding trauma. They may cause significant visual impairment. Corneal keloids occur in about 25% of patients, usually develop in children older than 5 years, and are bilateral in about one half of patients.

Many children with Lowe syndrome develop strabismus.

All boys have impaired vision; corrected acuity is rarely better than 20/100.

Examination of the nervous system

Neonatal generalized hypotonia due to CNS (brain) dysfunction is a consistent feature of OCRL. Feeding difficulties and delayed motor development may occur.

Although tone improves with age, most patients never achieve normal muscular tone and have consequential problems such as scoliosis and hernias.

Areflexia may also be present.

Decreased motor tone also results in delayed motor milestones. Independent ambulation occurs in approximately 25% of boys aged 3-6 years and in 75% by age 6-13 years. Some never walk and require the use of a wheelchair for mobility.[7]

Seizures may occur.

Orthopedic complications include hypophosphatemia and metabolic acidosis, which are causative factors in the development of bone disease. This bone disease includes rickets, osteomalacia, and osteopenia. Osteopenia is a consistent finding despite maintenance of normal serum phosphorus levels with therapy. Aside from osteopenia, the other bone manifestations can be prevented or ameliorated with treatment.

Fractures are common in boys with Lowe syndrome and often occur when they are learning how to walk. The femur is most often affected. About one third of patients with Lowe syndrome have more than one fracture. Osteopenia or osteoporosis may play a causative role in this propensity to fracture.

Joint swelling, arthritis, and tenosynovitis are common and typically occur in the late teenaged years and early adulthood. Nontender swelling of the small and large joints may occur. Plantar masses have also been reported. The cause of these abnormalities is unknown, and treatment is merely supportive.

Scoliosis is frequently present in patients with Lowe syndrome and may progress after puberty.

Both joint hypermobility and decreased movement that causes joint contractures have been reported.

Growth

Patients with Lowe syndrome have normal birth weights and lengths. However, severely diminished postnatal growth is typical, and, by age 1-3 years, growth parameters fall below the third percentile.

The average final adult height is 5'1".

Adult head circumferences are typically within the reference range.

Sexual development progresses at a normal pace.

Other significant physical examination findings

Cryptorchidism occurs in 15-40% of boys with Lowe syndrome.

Dermatologic and mucosal cysts may occur in multiple sites including the mouth, teeth (blue dome cysts), buttocks, and lower back. They can be painful and may become superinfected.

Delayed eruption of permanent teeth, crowding, hypoplastic enamel, constricted palate, taurodontism of the molars, dental caries, gingival inflammation due to mouth breathing, and excessive calculus deposits on teeth have been reported. Abnormal dentition due to excessive vertical facial length has been described in adult patients with Lowe syndrome. Dental cysts may occur.[8]

Causes

Lowe syndrome is an X-linked condition caused by mutations in the OCRL1 gene, which encodes inositol polyphosphate 5-phosphatase OCRL-1, which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P2). This enzyme appears to play a role in regulating protein trafficking, second messengers, and other aspects of cellular metabolism.

OCRL has been demonstrated to localize to the primary cilium. Recent research has shown that cilia from fibroblasts in patients with Lowe syndrome exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from a Lowe syndrome mouse model, as well as in Ocrl-null MEFs. Effects to the cilium may explain the multisystem nature of the condition.

Interestingly, OCRL1 mutation has been reported in 23% of kindreds with Dent-2 disease, which is another X-linked renal tubulopathy characterized by hypercalcuria and nephrocalcinosis.[6] A defect in the OCRL1 protein may cause the mildly elevated creatine kinase and lactate dehydrogenase (LDH) serum levels observed in this subgroup of patients, without the presence of cataract. Mitochondrial encephalomyopathies such as cytochrome oxidase deficiency can present similarly with hypotonia, mental retardation, cataracts, and renal tubular dysfunction.

Complications

Dental problems may occur.

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

The studies discussed below may be indicated in oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome.

Urinalysis, urinary electrolyte levels (including urine phosphorous and calcium levels), urinary amino acid levels, urine osmolality, and urinary carnitine levels

Renal tubular dysfunction (commonly described as Fanconi syndrome) is a cardinal manifestation of Lowe syndrome, but severity widely varies.

Proximal renal tubular acidosis due to bicarbonate loss in the urine has been reported.

Aminoaciduria varies in Lowe syndrome but is typically present.

Low molecular weight (LMW) proteinuria, such as retinol-binding protein and β2 microglobulin, are elevated in urine.

Albuminuria may be noted.

Hypercalcuria has been reported in patients with Lowe syndrome as part of the proximal tubulopathy or as a result of vitamin D treatment, leading to nephrocalcinosis or nephrolithiasis/urolithiasis.

Water resorption is impaired, resulting in high urine volume and low urine osmolality. Dehydration may be life threatening in the first years of life.

Hyperphosphaturia may lead to osteomalacia or rickets.

L-carnitine is lost in the urine. Whether carnitine wasting in the urine from severe Fanconi syndrome is the etiology of carnitine deficiency has not been studied adequately in Lowe syndrome.

Glycosuria is absent in the majority of patients with Lowe syndrome.

Plasma electrolyte levels

Clinically significant hypokalemia due to urinary losses is rare but may require replacement therapy.

Clinically significant hyponatremia and hypocalcemia are extremely rare.

Plasma alkaline phosphatase, calcium, and phosphorus levels and serum 25 hydroxy vitamin D level

Urinary losses of calcium and phosphorus predispose to the development of rickets and osteomalacia.

A rise in alkaline phosphatase levels is usually the first biochemical indicator of rickets.

Vitamin D deficiency due to lower exposure to sun is common in children and may worsen bone disease

Blood gas levels

Significant metabolic acidosis is caused by the urinary loss of bicarbonate.

Plasma carnitine levels

As carnitine is lost in the urine, plasma levels may be low and oral replacement therapy may be necessary.

Plasma creatinine levels and estimation of creatinine clearance

Progressive renal failure is heralded by a gradual increase in plasma creatinine and a decrease in creatinine clearance. The calculated glomerular filtration rate (GFR) using widely published formulas such as the Schwartz or the Schwartz Haycock formulas in children with Lowe syndrome were found to overestimate the true GFR due to low muscle mass. A lower k value in the corresponding formulas was suggested for use in patients with Lowe syndrome; for example, a k of .30 is used when creatinine is measured in mg/dL, and a k of 26 is used when creatinine is measured in mmol/L. Direct measurement of GFR using a renal glomerular marker such as iohexol or iothalamate is the preferred and accurate method to measure kidney function in patients with Lowe syndrome.

Other serum markers

Serum aspartate aminotransferase (AST), LDH, and creatine kinase levels are often elevated. AST and LDH levels may be 2-3 times the reference range.

Serum acid phosphatase levels may be elevated.

α-2 globulin levels may be abnormally elevated on serum protein electrophoresis findings.

Thyroxine (T4) levels, thyroxine-binding globulin (TBG) levels, and erythrocyte sedimentation rate (ESR) may be high.

Thrombocytopenia has been reported in Lowe syndrome and can be explained by the homology of the human OCRL protein to the phosphatidylinositol biphosphate 5-phosphatase present in human platelets, resulting in some functional overlap between these proteins.

Diagnostic testing

Measurement of inositol polyphosphate 5-phosphatase enzyme activity in cultured skin fibroblasts has been the preferred diagnostic test. Mutation analysis may be confirmatory and is increasingly used as the main diagnostic test. Few cases have been reported in females, who are more frequently carriers, with up to two-thirds of phenotypically significant cases secondary to a maternal carrier. Most affected females have X-autosomal translocations involving the OCRL1 locus with cytogenetic abnormalities (reciprocal translocation involving the X-chromosome), a 45,X karyotype, a uniparental disomy, or an extremely skewed X-inactivation, which subsequently permits full expression of the OCRL phenotype.

Imaging Studies

Brain MRI may demonstrate white matter abnormalities, particularly in the periventricular area. These signal abnormalities are caused by fluid-filled cysts, which appear to have no clinical significance. Tigroid pattern of white matter demyelination has been reported on MRI imaging and is thought to represent areas of normal white matter signaling interspersed with demyelinated areas.

Radiographs of the wrists and long bones may demonstrate changes that are typical of rickets, including metaphyseal flaring and osteopenia.

Renal imaging studies include the following:

  • Renal ultrasonography may show evidence of nephrocalcinosis or even nephrolithiasis.

  • Poor renal uptake of technetium 99 m (Tc99m) dimercaptosuccinic acid is reported in patients with Lowe syndrome.

Histologic Findings

Renal biopsies have demonstrated initial normal pathology with progression to tubular dilation around age 1-2 years and then subsequent increased glomerular cellularity, proteinaceous casts in tubular lumina, and focal glomerular sclerosis, as well as diffuse tubulointerstitial fibrosis in older children.

 

Treatment

Medical Care

Management of renal tubular acidosis in patients with oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, includes the following:

  • Careful monitoring of acid-base status and electrolyte levels is required. Alkali supplements, such as sodium bicarbonate, sodium citrate and citric acid (Bicitra), or sodium citrate and potassium citrate (Polycitra), are administered to maintain plasma bicarbonate levels at 22 mEq/L. The dose of sodium bicarbonate can vary from 1-10 mEq/kg/d divided into 3 or 4 doses. Potassium citrate is preferable in patients with hypercalcuria to decrease nephrocalcinosis and urinary calcium excretion.

  • Potassium and calcium supplementation may be required to offset renal losses.

  • Oral carnitine supplementation may be necessary if plasma levels are abnormally low.

Neutral phosphate and vitamin D supplementation and careful maintenance of normal acid-base status are necessary to avoid rickets and osteomalacia.

Acute illness with attendant risk of dehydration and electrolyte abnormalities should be treated with aggressive intravenous fluid and electrolyte therapy.

Cryptorchidism may improve with hormonal therapy.

Human growth hormone therapy may be used in patients with short stature to improve growth velocity.

Surgical Care

Ophthalmologic intervention

Removal of cataracts as early as possible, even within the first weeks of life, is indicated in order to provide the optimal visual stimulation to the developing brain.

Avoid corneal contact lenses because of associated risk of corneal keloid formation and complexities of contact lens care; artificial lens implants should also be avoided because of probable increased risk of glaucoma.

Glaucoma develops in about one half of all patients with Lowe syndrome and is typically difficult to treat. Surgical implantation of artificial valves to control the release of intraocular fluid is often required

Corneal keloids can interfere with vision. Treatment may consist of surgical removal of the scar tissue or radiation therapy. Corneal transplantation is problematic because of the difficulty in administering the required intensive postoperative care.

Surgical correction of strabismus is sometimes required.

Other procedures

If testes do not spontaneously descend in boys with cryptorchidism by age 5 years, surgical correction may be necessary.

Nasogastric tube feeding or gastrostomy (sometimes with fundoplication) may be indicated.

Resection of fibromas and cutaneous cysts is indicated if they are painful or impair function.

Consultations

Ophthalmologist: Because eye complications are a primary manifestation of Lowe syndrome, meticulous management by an ophthalmologist is necessary. Cataract surgery is usually performed within the first few weeks of life. In addition, close monitoring of intraocular pressure is necessary because glaucoma is common and requires treatment. Corrective contact lenses or glasses, with or without eye patches, are required to manage the visual deficits caused by cataracts and strabismus.

Nephrologist: Renal Fanconi syndrome typically develops in children aged 1 year and requires replacement therapy to offset renal losses. Renal failure gradually develops within the second decade of life.

Orthopedist: Scoliosis and lone-bone deformities due to rickets and contractures may require orthopedic consultation.

Endocrinologist: Various endocrine problems in Lowe syndrome, such as growth hormone and luteinizing hormone dysfunction, have been described. Early detection and testing of the HPG axis in patients with Lowe syndrome can predict gonadal abnormalities and growth delays from a younger age, which enhances the overall case management into adolescence.

Clinical geneticist/metabolic disease specialist: A clinical geneticist/metabolic disease specialist is typically familiar with this very rare disorder and can help facilitate and interpret diagnostic testing. The specialist should work with the nephrologist and ensure proper genetic counseling.

Diet

Some physicians have tried low-protein diets in an attempt to offset the renal disease, but a clear benefit from this diet has not been demonstrated. In general, a low-protein diet is not recommended in children because it may interfere with growth.

Long-Term Monitoring

Hypotonia and mental retardation in oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, necessitate physical, speech, and feeding therapy.

Physical therapy should be initiated in infancy. The initial goals may be head control, sitting, rolling over, and locomotion.

Speech delays are common and are multifactorial in origin. Contributing factors include hypotonia, high palate, and intellectual delays.

Hypotonia often causes feeding difficulties. Sucking, swallowing, and chewing may be impaired, and therapy may be helpful.

Services for the visually handicapped can be helpful.

Inpatient & Outpatient Medications

Replacement of renal losses is essential.

Sodium citrate and citric acid (Bicitra) is an alkalizing agent used to manage metabolic acidosis. The therapeutic goal is to maintain serum bicarbonate levels at 22 mEq/L.

Neutral phosphate and vitamin D supplements may be necessary to prevent the development of osteomalacia or rickets caused by phosphaturia and calciuria. If a serum 25 hydroxy vitamin D study shows a level lower than 30 ng/mL, ergocalciferol or cholecalciferol is given to correct the deficiency. Active vitamin D (calcitriol) may be added for therapy of bone disease.

Carnitine may be used if renal losses are substantial enough to cause abnormally low blood levels.

Anticonvulsants are necessary in patients with seizures. However, anticonvulsants can interfere with vitamin D metabolism; therefore, caution is necessary.

 

Medication

Medication Summary

Medications are necessary in oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, to offset the renal losses of electrolytes and other substances.

Minerals and electrolytes

Class Summary

These agents are used to correct disturbances in fluid and electrolyte homoeostasis or acid-base balance. They are also used to reestablish osmotic equilibrium of specific ions. Renal losses of calcium and phosphate may predispose to the development of osteomalacia and rickets.

Calcitriol (Rocaltrol)

Used to manage rickets and osteomalacia. A synthetic vitamin D analog (1 α, 25-dihydroxycholecalciferol or 1 α, 25-dihydroxyvitamin D3) that is active in regulating the absorption of calcium from the intestinal tract and its utilization in the body.

Sodium citrate and citric acid (Bicitra)

Systemic alkalizer solution used to treat renal tubular acidosis. Following ingestion, citrate salts are oxidized to bicarbonate. Each mL contains 1 mEq sodium ion and is equivalent to 1 mEq bicarbonate.

Phosphate salts (Neutra-Phos)

Increases serum phosphate levels and is used to manage rickets and osteomalacia. Serum phosphate is important in regulating serum calcium concentration. In patients with increased urinary excretion of phosphorus and calcium, neutral phosphorus is necessary to offset these losses and to prevent osteomalacia and rickets. One g of phosphorus equals 32.29 mmol.

Amino acids

Class Summary

These are essential cofactors of fatty acid metabolism. Oral carnitine may be used to replace urinary losses. Its efficacy in altering the outcome of patients with oculocerebrorenal syndrome of Lowe is unclear.

Levocarnitine (Carnitor)

A carrier molecule involved in the transport of long-chain fatty acids across the inner mitochondrial membrane.