Clinical Guidance

To date, correlation of genotype with phenotype has not been established. Differing clinical courses have been noted in unrelated individuals with the same OCRL pathogenic variant . It is also now apparent that pathogenic variants in OCRL that result in total loss of OCRL expression occur both in individuals with Lowe syndrome and in individuals with the allelic disorder, Dent disease, but there have not been families in which one affected male has Lowe syndrome and a male relative with the same pathogenic variant has Dent disease.

Source: GeneReviews — "Lowe Syndrome"

Penetrance

Penetrance is complete, with variability in severity of phenotype in affected males within any given family.

Source: GeneReviews — "Lowe Syndrome"

Diagnostic Criteria

Suggestive Findings

Lowe syndrome should be suspected in a proband with a combination of the following features:

• Bilateral dense congenital cataracts

• Infantile congenital hypotonia

• Delayed development

• Proximal renal tubular transport dysfunction of the Fanconi type characterized by low molecular-weight (LMW) proteinuria (including retinol binding protein, N-acetyl glucosaminidase, and albumin), aminoaciduria and varying degrees of bicarbonaturia and acidosis, phosphaturia and hypophosphatemia, and hypercalciuria.

Source: GeneReviews — "Lowe Syndrome"

Differential Diagnosis

Low molecular-weight (LMW) proteinuria is a feature of Fanconi syndrome and can also be seen in other conditions including cystinosis, nephrotoxic drug injury to the tubules (e.g., aminoglycosides), and acute tubulointerstitial renal transplant rejection with tubular injury. However, the LMW proteinuria appears to be a more prominent feature of renal tubular dysfunction in Lowe syndrome and Dent disease than in these other disorders. Like Lowe syndrome, generalized congenital infections (e.g., rubella) are associated with a combination of congenital or neonatal-onset cataracts, hypotonia, proximal renal tubular dysfunction, and/or delayed development and should be considered in the differential diagnosis of Lowe syndrome. Genetic disorders that may be associated with these features are summarized in . Table 2. Disorders to Consider in the Differential Diagnosis of Lowe Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Lowe syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with Lowe Syndrome

System/Concern | Evaluation | Comment

Eyes | Ophthalmologic exam to assess for cataract glaucoma | Behavior problems may necessitate use of anesthesia for exam.

CNS | • Developmental behavior assessments

• EEG if seizures present to optimize therapy

|

Kidneys

| Assess renal tubular function. | Tests should incl:

• Serum electrolytes, glucose, calcium, phosphorus, creatinine

• Simultaneous urinalysis, urine pH, sodium, potassium, chloride, calcium, phosphorus, creatinine, amino acids, protein retinol-binding protein, /or N-acetyl glucosaminidase (if available)1

If hematuria or hypercalciuria is present, renal ultrasound to look for nephrolithiasis or nephrocalcinosis. |

If aciduria or phosphaturia present, test serum 1,25-dihydroxy vitamin D parathyroid hormone plus bone radiographs to evaluate for renal rickets. |

Growth/

Feeding

| • Growth parameters

• Infants assessed for feeding problems gastroesophageal reflux, incl a pH probe study

|

Skeletal

| Radiographs for bone pain or point tenderness to evaluate for fractures |

Dental

| Thorough clinical exam after tooth eruption | Generalized mobility of all primary teeth as well as subrachitic changes due to renal rickets

Hematologic

|...

Source: GeneReviews — "Lowe Syndrome"

Clinical Guidance

Corneal contact lenses. Because of the associated risks of corneal keloid formation and the inherent difficulties that the person with Lowe syndrome has in managing personal contact lens care, conventional eye glasses seem safer than corneal contact lenses. Artificial lens implants. Although some infants have had primary intraocular lens implantation at the time of cataract surgery, the associated risk of glaucoma appears higher in those infants with artificial lens implants. Therefore, artificial lens implants should be used with extreme caution, with intraocular pressure carefully monitored (under anesthesia if required) on a continual basis.

Source: GeneReviews — "Lowe Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Lowe Syndrome"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with Lowe Syndrome

System/Concern | Evaluation | Frequency

Eyes | Intraocular pressure monitoring | Every 6 mos life long

Other ophthalmic eval | • As determined by specialist based on type severity of eye abnormality

• Promptly w/any signs of intraocular pressure (e.g., excessive tearing, eye rubbing, change in clarity/transparency of cornea)

CNS | Developmental progress assessed educational plan updated | 2x/yr for 1st 3 yrs, then annually

Brain imaging for any regression in abilities |

Kidneys

| Kidney function assessment1 | At least annually

• If on supplemental bicarbonate or citrate, phosphorus or calcitriol or other vitamin D analog, need kidney function assessment1 w/blood urine tests

• May need serum vitamin D-25 hydroxy to assess for parent vitamin D deficiency

| Every 3-6 mos; more often after dose changes

Radiographs of long bones growth plates if renal bone disease is present | Regular intervals as needed, but no more than every 6 mos

Growth

| Height/length weight | • Every 1-2 mos in infants

• Every 3-6 mos in older children adolescents

• Every 3 mos if on growth hormone

Skeletal

| Monitor scoliosis joint hypermobility | Annually

Dental

| Exams by pediatric dentist | 2x/yr

1. Testing includes measurement of (a) serum concentrations of electrolyte, blood urea nitrogen (BUN), creatinine, calcium, phosphorus, albumin, intact parathyroid hormone, and 1,25-dihydroxyvitamin D and (b) urinalysis and random urine protein, calcium, and creatinine.

Source: GeneReviews — "Lowe Syndrome"