ABSTRACT
The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and proximal renal tubular dysfunction. Whereas the ocular manifestations and severe muscular hypotonia are the typical first diagnostic clues apparent at birth, the manifestations of incomplete renal Fanconi syndrome are often recognized only later in life. Other characteristic features are progressive severe growth retardation and behavioral problems, with tantrums. Many patients develop a debilitating arthropathy. Treatment is symptomatic, and the life span rarely exceeds 40 years. The causative oculocerebrorenal syndrome of Lowe gene (OCRL) encodes the inositol polyphosphate 5-phosphatase OCRL-1. OCRL variants have not only been found in classic Lowe syndrome, but also in patients with a predominantly renal phenotype classified as Dent disease type 2 (Dent-2). Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for the loss of enzyme function. Extensive research has demonstrated that OCRL-1 is involved in multiple intracellular processes involving endocytic trafficking and actin skeleton dynamics. This explains the multi-organ manifestations of the disease. Still, the mechanisms underlying the wide phenotypic spectrum are poorly understood, and we are far from a causative therapy. In this review, we provide an update on clinical and molecular genetic findings in Lowe syndrome and the cellular and physiological functions of OCRL-1.
Subject(s)
Oculocerebrorenal Syndrome/therapy , Adolescent , Child , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 11 , Humans , Infant , Infant, Newborn , Molecular Biology , Mutation , Oculocerebrorenal Syndrome/genetics , Oculocerebrorenal Syndrome/pathology , WAGR SyndromeSubject(s)
Oculocerebrorenal Syndrome , Chromosomes, Human, X/genetics , Diagnosis, Differential , Female , Humans , Male , Oculocerebrorenal Syndrome/diagnosis , Oculocerebrorenal Syndrome/genetics , Oculocerebrorenal Syndrome/physiopathology , Oculocerebrorenal Syndrome/therapy , Phosphoric Monoester Hydrolases/genetics , Prognosis , Translocation, GeneticSubject(s)
Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 18/genetics , Cryptorchidism , Oculocerebrorenal Syndrome , Trisomy , Cryptorchidism/diagnosis , Cryptorchidism/epidemiology , Cryptorchidism/etiology , Cryptorchidism/physiopathology , Female , Humans , Male , Mutation , Oculocerebrorenal Syndrome/diagnosis , Oculocerebrorenal Syndrome/etiology , Oculocerebrorenal Syndrome/physiopathology , Oculocerebrorenal Syndrome/therapy , Phosphoric Monoester Hydrolases/genetics , Prognosis , SyndromeABSTRACT
Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years.
Subject(s)
Oculocerebrorenal Syndrome/diagnosis , Oculocerebrorenal Syndrome/therapy , Adolescent , Adult , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/therapy , Child , Child, Preschool , Diagnosis, Differential , Eye Diseases/diagnosis , Eye Diseases/therapy , Female , Genetic Carrier Screening/methods , Humans , Infant , Infant, Newborn , Kidney Diseases/diagnosis , Kidney Diseases/therapy , Middle Aged , Oculocerebrorenal Syndrome/etiology , Phosphatidylinositols/deficiency , Phosphoric Monoester Hydrolases/genetics , Pregnancy , Prenatal Diagnosis/methods , Prognosis , Quality of Life , Young AdultABSTRACT
El síndrome de Lowe, o síndrome oculocerebrorrenal, es una enfermedad hereditaria recesiva asociada al cromosoma X. Se caracteriza por defectos oculares (cataratas congénitas, glaucoma), defectos del sistema nervioso central (hipotonía generalizada con hiporreflexia y retraso mental severo) y alteraciones renales (disfunción tubular progresiva con acidosis e hiperaminoaciduria). En este artículo presentamos el caso de una mujer portadora asintomática del síndrome de Lowe y las repercusiones que esto conlleva en su historia obstétrica (AU)
Lowe Syndrome, or oculo-cerebro-renal syndrome is a rare X-linked disorder. It is characterized by ocular defects (congenital cataracts, glaucoma), central nervous defects (generalized muscular hypotonia, hyporeflexia, and severe mental retardation), and renal disorders (progressive tubular dysfunction with acidosis and hyperaminoaciduria). This article presents the case of an asymptomatic female carrier and her obstetric consequences (AU)
Subject(s)
Female , Adult , Humans , Oculocerebrorenal Syndrome/therapy , X Chromosome/genetics , Oculocerebrorenal Syndrome , Ultrasonography, Doppler, Color/methods , Umbilical Arteries , X Chromosome/pathology , X Chromosome , Intellectual Disability/complications , Intellectual Disability/diagnosis , Hereditary Sensory and Motor Neuropathy/complications , Ocular Hypotension/complications , Cataract Extraction/methods , Cataract/complications , Cataract/physiopathology , Glaucoma/complicationsSubject(s)
Oculocerebrorenal Syndrome , Adolescent , Adult , Behavior , Child , Child, Preschool , Chromosome Mapping , Eye Diseases , Forecasting , Genetic Carrier Screening , Genetic Counseling , Humans , Infant , Intelligence , Male , Musculoskeletal Diseases , Nervous System Diseases/physiopathology , Oculocerebrorenal Syndrome/diagnosis , Oculocerebrorenal Syndrome/genetics , Oculocerebrorenal Syndrome/physiopathology , Oculocerebrorenal Syndrome/therapy , Prenatal Diagnosis , ResearchABSTRACT
We report clinical features and course of Lowe's syndrome with regard to three cases. All of them are males and clear inherited transmission was demonstrated in patients 2 and 3 and was suggested in patient 1. Age at the moment of diagnosis oscillated between 7 and 18 years. The three cases showed weight and height percentiles under p 3. Congenital bilateral cataract and search nystagmus were found in all of them. Profound mental retardation, muscular hypotonicity and diminished or absent tendon reflexes constituted distinctive findings in the neurological area. Among renal manifestations stood out proteinuria, generalized hyperaminoaciduria and tubular renal acidosis, they carried from rickets and growth failure. Cases 1 and 2 has characteristic facies. Patient 1 died after series of recurrent bronchial and pulmonary infections: death happened during Fanconi's syndrome evolution. Cases 2 and 3 are in a stabilized period, with a longer life expectation, although they suffer from residual moderate renal failure.
