Lowe Syndrome
Summary
Clinical characteristics.
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including low molecular-weight (LMW) proteinuria, aminoaciduria, bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, hypercalciuria, sodium and potassium wasting, and polyuria. The features of symptomatic Fanconi syndrome do not usually become manifest until after the first few months of life, except for LMW proteinuria. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease between the second and fourth decades of life.
Diagnosis/testing.
The diagnosis of Lowe syndrome is established in a male proband with typical clinical and laboratory findings and a hemizygous pathogenic variant in OCRL identified by molecular genetic testing. The diagnosis of Lowe syndrome is rare in females but can be established in a female proband who demonstrates the same clinical and laboratory findings as a male proband and who is found to have a heterozygous pathogenic variant in OCRL by molecular genetic testing.
Management.
Treatment of manifestations:
- Early removal of cataracts with postoperative glasses; management of glaucoma; early infant therapy, preschool intervention program and individualized education program throughout schooling; behavior modification plan; anticonvulsant therapy if seizures are present.
- Treatment of renal tubular dysfunction includes oral supplements of sodium and potassium bicarbonate or citrate to correct acidosis and hypokalemia, and oral phosphate and oral calcitriol (1,25-dihydroxyvitamin D3) to correct hypophosphatemia and renal rickets; treatment of ESRD with chronic dialysis and renal transplant in selected individuals.
- Consider human growth hormone therapy to improve growth velocity; tube feedings may be needed to treat infant feeding problems associated with hypotonia; standard treatment for gastroesophageal reflux if present. Bracing or surgery for severe or progressive scoliosis or joint hypermobility; resection of fibromas and cutaneous cysts if painful or impairing function.
Surveillance: Intraocular pressure monitoring every six months for life, other eye evaluations at intervals determined by specialist; at least annual assessment of kidney function, growth, developmental progress; annual evaluation for scoliosis and joint problems; semiannual dental examinations.
Circumstances to avoid: Corneal contact lenses because of associated risk of corneal keloid formation and complexities of contact lens care; artificial lens implants because of probable increased risk of glaucoma.
Genetic counseling.
Lowe syndrome is inherited in an X-linked manner. De novo pathogenic variants have been reported in 32% of males affected with Lowe syndrome. A high risk of germline mosaicism (4.5%) has been identified. When a mother is a heterozygous, each pregnancy has a 25% chance of an affected son, a 25% chance of a heterozygous daughter, a 25% chance of an unaffected son, and a 25% chance of a daughter who is not heterozygous. No affected male is known to have reproduced. Approximately 95% of heterozygous females older than age 15 years have characteristic findings in the lens of the eye on slit lamp examination by an experienced ophthalmologist using both direct and retroillumination. Once the OCRL pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
Diagnosis
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.
Note: LMW proteinuria, characterized by the excretion of proteins such as retinal binding protein and N-acetyl glucosaminidase, is seen in Lowe syndrome, the allelic disorder Dent disease (see Genetically Related Disorders), and many other diseases associated with the Fanconi syndrome. In Lowe syndrome, LMW proteinuria can be seen early in life even in the absence of clinically significant aminoaciduria or other renal tubular abnormalities [Laube et al 2004]. Thus, LMW may be the most sensitive early marker of the renal dysfunction occurring in this disorder.
Establishing the Diagnosis
Male proband. The diagnosis of Lowe syndrome is established in a male proband with typical clinical and laboratory findings and a hemizygous pathogenic variant in OCRL identified by molecular genetic testing (see Table 1).
Note: If a variant of unknown significance or no pathogenic variant is identified in a male with a clinical diagnosis consistent with Lowe syndrome, testing of inositol polyphosphate 5-phosphatase OCRL-1 activity in cultured skin fibroblasts is a possible option. Affected males have less than 10% normal activity of the enzyme. Such testing is abnormal in more than 99% of affected males and was shown to have high negative predictive value for Lowe syndrome in individuals referred with only partial overlap with Lowe syndrome phenotype who had no pathogenic variant found in OCRL [Hichri et al 2011].
Female proband. The diagnosis of Lowe syndrome in females is rare but can be established in a female proband with the same clinical and laboratory findings as a male proband and a heterozygous pathogenic variant in OCRL identified by molecular genetic testing. If a diagnosis of Lowe syndrome is established in a female, it is recommended that the clinician search for two pathogenic variants (one on each X chromosome) or an X-autosome translocation or other biologic cause for highly skewed inactivation of the X chromosome carrying the normal allele in a female heterozygote [Mueller et al 1991, Cau et al 2006].
Molecular Genetic Testing
Approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Lowe syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with atypical features or in whom the diagnosis of Lowe syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
Option 1. When the phenotypic and laboratory findings suggest the diagnosis of Lowe syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
- Single-gene testing. Sequence analysis of OCRL detects small intragenic deletions/insertions and missense, nonsense, and splice site variants. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.Note: Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
- A multigene panel that includes OCRL and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Option 2. When the diagnosis of Lowe syndrome is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Table 1.
Molecular Genetic Testing Used in Lowe Syndrome
| Gene 1 | Method | Proportion of Probands with a Pathogenic Variant 2 Detectable by Method |
|---|---|---|
| OCRL | Sequence analysis 3, 4 | ~95% 5 |
| Gene-targeted deletion/duplication analysis 6 | ~5% 5 | |
| Karyotype | Rare 7 |
- 1.
See Table A. Genes and Databases for chromosome locus and protein.
- 2.
See Molecular Genetics for information on allelic variants detected in this gene.
- 3.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
- 4.
Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
- 5.
Monnier et al [2000], Hichri et al [2011], Recker et al [2015]
- 6.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
- 7.
Translocations between an autosome and an X chromosome with a breakpoint through OCRL (Xq26.1) have been observed in females with Lowe syndrome [Hodgson et al 1986, Reilly et al 1988, Mueller et al 1991]; therefore, in an individual with Lowe syndrome in whom a pathogenic variant has not been detected by other methods, karyotype may be considered.
Clinical Characteristics
Clinical Description
Usually only males have the disorder. A few affected females with the clinical manifestations of Lowe syndrome have been reported [Cau et al 2006].
The major clinical manifestations found in males with Lowe syndrome involve the eyes, central nervous system, and kidneys. Nearly all post-pubertal heterozygous females have lens opacities; a few will have additional findings. With the wide availability of molecular genetic testing, phenotypic heterogeneity appears to be substantially greater than previously suspected, such that individuals who lack certain features of Lowe syndrome can still have pathogenic variants in OCRL.
Males
Eyes. Dense congenital cataracts, formed as a result of abnormal metabolism or migration of the embryonic lens epithelium, are found in all affected boys. Although present at birth, the cataracts may not be detected until a few weeks of life. Rarely, the lens opacities are so mild that they do not affect visual development, even into the teen years.
- Microphthalmos and enophthalmos, related to the lens abnormality, are noted occasionally.
- Infantile glaucoma, present in approximately 50% of affected males, is difficult to control and often results in buphthalmos (enlarged eyes) and progressive visual loss [McSpadden 2000, Nussbaum & Suchy 2001]. Often the glaucoma is not detected until after the lenses have been removed. The glaucoma is severe and requires surgical, rather than medical, management.
- Strabismus, retinal dystrophy, secondary corneal scarring, and calcific band keratopathy with keloid formation [Cibis et al 1982] may cause additional visual impairment [McSpadden 2000, Nussbaum & Suchy 2001].
All boys have impaired vision; corrected acuity is rarely better than 20/100 [McSpadden 2000, Nussbaum & Suchy 2001]. With decreased visual acuity, nystagmus develops early in life, even with early and uncomplicated surgery. Self-stimulatory activity also increases, i.e., rhythmic flapping of the hands, eye rubbing, and repetitive rocking movements. Despite aggressive intervention, visual disability may progress to blindness.
Central nervous system. Generalized infantile hypotonia is noted soon after birth and is of central origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but neither normal motor tone nor strength is ever achieved.
- Feeding difficulties in infancy associated with poor head control, sucking, or swallowing may be a consequence of the hypotonia.
- Decreased motor tone also results in delayed motor milestones. Independent ambulation occurs in approximately 25% of boys between age three and six years and in 75% by age six to 13 years. Some never walk, requiring the use of a wheelchair for mobility [McSpadden 2000].
Approximately 50% of affected boys have seizure disorders, most often of the generalized type and usually starting before age six years [McSpadden 2000].
Behavior problems (i.e., self-stimulation or stereotypic and obsessive-compulsive behaviors) are frequent and include many problems common to visually and intellectually handicapped individuals. Occasionally, violent tantrums or aggressive and self-abusive behaviors occur [Charnas & Gahl 1991, Kenworthy et al 1993].
Almost all affected males have some degree of intellectual impairment. Between 10% and 25% of affected males function in the low-normal or borderline range, approximately 25% function in the mild-to-moderate range, and 50%-65% function in the severe-to-profound range of intellectual disability [Kenworthy et al 1993]. Delayed language development is evident in early childhood. Most individuals learn to communicate verbally to some extent by age seven years; some eventually become quite verbal [McSpadden 2000]. Love of music and rhythm are notable.
As adults, most affected men reside with their families. A few are functional enough to live in a group home or even independently with appropriate assistance and guidance.
Kidneys. Affected boys have varying degrees of proximal renal tubular dysfunction of the renal Fanconi type. The features of symptomatic Fanconi syndrome do not usually become manifest until after the first few months of life, except for low molecular-weight (LMW) proteinuria.
- LMW proteins are normally filtered by the glomerulus, then reabsorbed in the proximal tubule through endocytosis and metabolized in lysosomes in proximal tubular cells.
- When reabsorption and/or metabolism are dysfunctional, LMW proteins, including retinol-binding protein, beta-2-microglobulin, and the lysosmal enzyme N-acetyl glucosaminidase, are lost in the urine. LMW proteinuria has been identified as early as just after birth [Laube et al 2004] and may be the most sensitive early marker for renal involvement of Lowe syndrome.
The molecular size of albumin is at the upper end of the size range for LMW proteins, so the small percentage of albumin that is normally filtered by the glomerulus is also reabsorbed and metabolized by the proximal tubule via the LMW protein transport process.
In Lowe syndrome, proximal renal tubular dysfunction often leads to clinically apparent albuminuria (urine dipstick albumin 1-4+; nephrotic range proteinuria >1 g/m2/day in more than half), while serum albumin remains normal [Bökenkamp & Ludwig 2016]. Albuminuria is better known as a marker of glomerular injury in other diseases such as diabetes mellitus; in Lowe syndrome it likely reflects proximal tubular dysfunction, especially early in life before chronic renal failure occurs.
All boys have LMW proteinuria and albuminuria, likely due to downstream disordered endocytosis and postendocytic membrane trafficking in the proximal tubular cell [Cui et al 2010, De Matteis et al 2017]. Most boys have aminoaciduria [Bökenkamp & Ludwig 2016]. Some boys develop full-blown renal Fanconi syndrome with bicarbonaturia and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, sodium and potassium wasting, and polyuria with an apparent urine-concentrating defect from the massive solute loss in the urine. Few of these boys have renal glucose wasting, which is frequently observed in other diseases with full-spectrum renal Fanconi syndrome [Bockenhauer et al 2008, Bökenkamp & Ludwig 2016, Zaniew et al 2018]. Other boys have little or no bicarbonaturia and phosphaturia, but LMW proteinuria and hypercalciuria with nephrocalcinosis and nephrolithiasis (calcium oxalate and calcium phosphate stones) similar to Dent disease [Bockenhauer et al 2008, Bökenkamp & Ludwig 2016].
Progressive glomerulosclerosis likely results from progressive renal tubular injury, which eventually may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) between the second and fourth decades of life [McSpadden 2000, Nussbaum & Suchy 2001, Zaniew et al 2018].
Life span. Most males do not live past age 40 years. In older individuals, death has been related to progressive renal failure or scoliosis. Death from dehydration, pneumonia, and infections occurs at all ages [McSpadden 2000].
Short stature. Although birth length is usually normal, linear growth velocity is below normal and short stature becomes evident by age one year. The average adult height is approximately 155 cm [McSpadden 2000]. CKD and acidosis along with renal rickets or other bone disease may contribute to the short stature. Some boys have been treated with growth hormone, resulting in an increase in height but persistence of short stature for age [Zaniew et al 2018].
Feeding and gastrointestinal concerns
- Slow weight gain may occur because of insufficient caloric intake.
- Gastroesophageal reflux, most common in infancy, may be seen at any age.
- Aspiration of food along with a decreased ability to cough effectively to clear lung fields may lead to atelectasis, pneumonia, or chronic lung disease.
- Poor abdominal muscle tone increases the risk for chronic constipation and the development of (predominantly inguinal) hernias.
Bone disease in affected boys may be related to Fanconi syndrome with phosphaturia, inadequate renal production of 1,25-dihydroxyvitamin D, and chronic acidosis as well as CKD. The bone disease may appear as classic changes of rickets on bone radiographs.
However, even in the presence of well-corrected Fanconi syndrome and no findings of rickets, some boys have repeat pathologic bone fractures with poor healing and bone demineralization on radiographs or bone densitometry [E Brewer, personal observation].
Whether some of the bone disease is related to inactivity resulting from muscle hypotonia and immobilization in severely affected boys or to a primary defect in bone mineralization/molecular transport requires further study.
Other musculoskeletal concerns
- Decreased truncal motor tone increases the risk of developing scoliosis, present in approximately 50% of affected boys [McSpadden 2000].
- Hypermobile joints may result in joint dislocation, especially of the hips and knees.
- In affected teenagers and adults, joint swelling, arthritis, tenosynovitis, and subcutaneous benign fibromas, often on the hands and feet and most especially in areas of repeated trauma, are noted frequently [Athreya et al 1983, Elliman & Woodley 1983].
- Elevated serum creatine kinase (CK), AST, and LDH are typical in Lowe syndrome and likely due to abnormal muscle metabolism [Charnas et al 1991, Bökenkamp & Ludwig 2016]. Decreased plasma carnitine concentration has been reported in approximately one third of individuals with Lowe syndrome [Charnas et al 1991], but the need for or efficacy of carnitine supplementation has never been studied, and therapy continues to be individualized.
Genitourinary issues
- Undescended testes (cryptorchidism) are noted in approximately one third of affected boys [McSpadden 2000, Recker et al 2015]. Isolated LH elevation at baseline and on GnRH stimulation testing was observed in an infant with undescended testes [Warner et al 2017].
- Puberty may be delayed in onset; otherwise, male secondary sexual development is normal.
Teeth and skin findings. Dental malformations and generalized mobility of primary teeth with decreased or dysplastic dentin formation may also be related to a primary dental abnormality in Lowe syndrome [Harrison et al 1999].
Superficial cysts may occur in the mouth and on the skin, especially the scalp, lower back and buttocks.The skin cysts may become painful and occasionally infected. Histologic examination revealed epidermal cysts in which the dermis was lined by several layers of stratified squamous epithelium with a granular layer and filled with keratin flakes [Ikehara & Utani 2017]. Cysts have also been found in imaging studies of the kidneys and brain. These findings suggest that an abnormality in connective tissue may also be involved in the pathogenesis of the disorder [McSpadden 2000, Kim et al 2014, Murakami et al 2018].
Coagulation disorder. The OCRL-1 protein is found in human platelets. Prolonged or delayed bleeding following surgery, such as cataract extraction has been reported. An intrinsic platelet defect in these individuals that can be detected using a platelet function analyzer (PFA-100) was identified; other coagulation profile related tests, including platelet counts, gave normal results [Lasne et al 2010]. In another study, thrombocytopenia/low normal platelets were found in about 20% [Recker et al 2015].
Females
Approximately 95% of postpubertal heterozygous females have characteristic findings in the lens of each eye on slit lamp examination through a dilated pupil by an experienced ophthalmologist. The lens findings have correlated with the results of molecular genetic studies in predicting heterozygosity for the pathogenic variant in OCRL in postpubertal females [Lin et al 1999, McSpadden 2000, Röschinger et al 2000, Nussbaum & Suchy 2001]. While the lens findings may appear in prepubertal females as well (especially the less common axial posterior central opacity), their absence does not exclude the possibility of heterozygosity.
Most heterozygous females show numerous irregular, punctate, smooth, off-white (white to gray) opacities, present in the lens cortex, more in the anterior cortex than the posterior cortex, and distributed in radial bands that wrap around the lens equator. Classically, the nucleus is spared. On retroillumination, the opacities are distributed in a radial, spoke-like pattern and can be relatively dense in a wedge shape comparable to an hour or two on the face of a clock, alternating with a similar-sized wedge with few to no opacities.
A few heterozygous females (~10%) have a dense central precapsular dead-white cataract at the posterior pole of the lens that may be visually significant if it is large. Similarly, the cataracts in some heterozygous females may become visually significant by the fourth decade and require surgery without the diagnostic importance being recognized.
The manifestations of Lowe syndrome besides those seen in the lens are not observed in heterozygous females unless there is either rare X;autosome translocation with the X chromosome breakpoint at OCRL or extremely skewed X inactivation. In an example of the latter, a female with two structurally normal X chromosomes showed classic, severe Lowe syndrome as a result of a familial defect in X inactivation inherited from her father. The paternally derived X chromosome containing a normal OCRL gene remained inactive in 100% of cells, while the maternally derived X chromosome carrying a pathogenic variant of ORCL was active in 100% of cells tested [Cau et al 2006].
Genotype-Phenotype Correlations
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 [Leahey et al 1993]. 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.
Penetrance
Penetrance is complete, with variability in severity of phenotype in affected males within any given family.
Nomenclature
Oculocerebrorenal syndrome, the formal term for this disorder, is synonymous with Lowe syndrome, and may be preferred to avoid eponymous syndrome nomenclature.
Prevalence
Lowe syndrome is an uncommon, pan ethnic disorder with an estimated prevalence of 1:500,000 in the general population, based on observations of the American Lowe Syndrome Association and the Italian Association of Lowe syndrome [Bökenkamp & Ludwig 2016].
The disorder has been seen in America, Europe, Australia, Japan, and India and is believed to occur worldwide.
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.
Table 2.
Disorders to Consider in the Differential Diagnosis of Lowe Syndrome
| Differential Diagnosis Disorder | Gene(s) | MOI | Clinical Features of Differential Diagnosis Disorder | |
|---|---|---|---|---|
| Overlapping w/Lowe syndrome | Distinguishing from Lowe syndrome | |||
| Zellweger spectrum disorder | PEX1 PEX6 PEX12 PEX26 PEX10 PEX2 PEX5 PEX13 PEX16 PEX3 PEX19 PEX14 PEX11β | AR |
|
|
| Nance-Horan syndrome (OMIM 302350) | NHS | XL |
|
|
| Smith-Lemli-Opitz syndrome | DHCR7 | AR |
| Multiple major & minor malformations including:
|
| Congenital myotonic dystrophy type 1 | DMPK | AD |
|
|
| Disorders of mitochondrial oxidative phosphorylation 3 | See footnote 1 | See footnote 1 |
|
|
| Cystinosis | CTNS | AR |
|
|
| Donnai-Barrow syndrome | LRP2 | AR |
|
|
AD = autosomal dominant; AR = autosomal recessive; CKD = chronic kidney disease; DD = developmental delay; ID = intellectual disability; LMW = low molecular-weight; MOI = mode of inheritance; mt = mitochondrial; RTA = renal tubular acidosis; SNHL = sensorineural hearing loss; XL = X-linked
- 1.
Mitochondrial disorders may be caused by defects of nuclear DNA or mtDNA: nuclear gene defects may be inherited in an autosomal recessive, autosomal dominant, or X-linked manner, mitochondrial DNA defects are transmitted by maternal inheritance.
- 2.
Cystine-depleting therapy begun just after birth can attenuate the Fanconi syndrome.
- 3.
Finsterer & Scorza [2017]
- 4.
Anglani et al [2018]
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with Lowe syndrome, the evaluations summarized in Table 3 (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 |
| |
| Kidneys | Assess renal tubular function. | Tests should include:
|
| If hematuria or hypercalciuria is present, renal ultrasound to look for nephrolithiasis or nephrocalcinosis. | ||