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World Journal of Pediatrics : WJP Jul 2023Fanconi-Debré-de Toni syndrome (also known as Fanconi renotubular syndrome, or FRST) profoundly increased the understanding of the functions of the proximal convoluted... (Review)
Review
BACKGROUND
Fanconi-Debré-de Toni syndrome (also known as Fanconi renotubular syndrome, or FRST) profoundly increased the understanding of the functions of the proximal convoluted tubule (PCT) and provided important insights into the pathophysiology of several kidney diseases and drug toxicities.
DATA SOURCES
We searched Pubmed and Scopus databases to find relevant articles about FRST. This review article focuses on the physiology of the PCT, as well as on the physiopathology of FRST in children, its diagnosis, and treatment.
RESULTS
FRST encompasses a wide variety of inherited and acquired PCT alterations that lead to impairment of PCT reabsorption. In children, FRST often presents as a secondary feature of systemic disorders that impair energy supply, such as Lowe's syndrome, Dent's disease, cystinosis, hereditary fructose intolerance, galactosemia, tyrosinemia, Alport syndrome, and Wilson's disease. Although rare, congenital causes of FRST greatly impact the morbidity and mortality of patients and impose diagnostic challenges. Furthermore, its treatment is diverse and considers the ability of the clinician to identify the correct etiology of the disease.
CONCLUSION
The early diagnosis and treatment of pediatric patients with FRST improve the prognosis and the quality of life.
Topics: Humans; Child; Fanconi Syndrome; Quality of Life; Cystinosis; Oculocerebrorenal Syndrome; Kidney Diseases
PubMed: 36729281
DOI: 10.1007/s12519-023-00685-y -
Ophthalmology. Glaucoma 2024Ultrasound biomicroscopy comparison of two infants with Lowe oculocerebrorenal syndrome, one with glaucoma and one without, found differences in corneal curvature, iris...
Ultrasound biomicroscopy comparison of two infants with Lowe oculocerebrorenal syndrome, one with glaucoma and one without, found differences in corneal curvature, iris thickness, trabecular-iris angle, and lens morphology are potential glaucoma-associated features.
Topics: Humans; Oculocerebrorenal Syndrome; Glaucoma; Cataract
PubMed: 37364636
DOI: 10.1016/j.ogla.2023.06.010 -
Special Care in Dentistry : Official... 2024Lowe syndrome (LS) is an uncommon condition that affects the brain, kidneys, nervous system, and eyes, predominantly in males. The aim of this study was to examine... (Observational Study)
Observational Study
INTRODUCTION
Lowe syndrome (LS) is an uncommon condition that affects the brain, kidneys, nervous system, and eyes, predominantly in males. The aim of this study was to examine dental conditions, dental treatments, and access and/or barriers to care for those with LS compared to healthy individuals.
METHODS
Surveys assessing dental conditions, dental treatments, and access and/or barriers to care were administered to families in the Lowe Syndrome Association and families with healthy children who had dental appointments at the Tufts University School of Dental Medicine (TUSDM) pediatric dental clinic. One parent or a guardian of pediatric patients with LS or not at TUSDM was asked to complete an online survey.
RESULTS
One hundred and eight surveys were obtained (n:58 from the LS group and n:50 from the healthy group). The LS group was significantly more likely (p < .05) to report "crooked/misaligned teeth," "difficult time chewing," "bad breath," and "mouth cysts" and was significantly less likely to report 6-month examination, "cleaning," and "filling." The LS group reported significantly greater difficulty locating a dentist.
CONCLUSION
The findings of this study indicate that individuals with LS are more vulnerable to developing severe dental conditions and experiencing difficulties in accessing dental care than healthy individuals. Additionally, those who present with this syndrome may be less likely to receive specific necessary dental treatments. As a result, it is essential to offer appropriate dental care and support to individuals with LS to guarantee they achieve optimal oral health.
Topics: Male; Child; Humans; Oculocerebrorenal Syndrome; Oral Health; Surveys and Questionnaires; Health Status; Health Services Accessibility
PubMed: 37128874
DOI: 10.1111/scd.12870 -
Pediatric Nephrology (Berlin, Germany) Aug 2024Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of...
BACKGROUND
Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of an atypical phenotype, investigates the genetic characteristics of eight children diagnosed with Lowe syndrome in southern China, and performs functional analysis of the novel variants.
METHODS
Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants.
RESULTS
In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation.
CONCLUSION
This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome.
Topics: Humans; Oculocerebrorenal Syndrome; Male; Phenotype; Female; Child; Phosphoric Monoester Hydrolases; China; Child, Preschool; Retrospective Studies; Exome Sequencing; Infant; Adolescent; Mutation; Asian People; Codon, Nonsense; East Asian People
PubMed: 38589698
DOI: 10.1007/s00467-024-06356-y -
Oral Surgery, Oral Medicine, Oral... Dec 2023Lowe syndrome (LS) is a rare disease (1:500,000) with X-linked recessive inheritance involving the kidneys, eyes, and nervous system. A Mexican 25-year-old male patient... (Review)
Review
Lowe syndrome (LS) is a rare disease (1:500,000) with X-linked recessive inheritance involving the kidneys, eyes, and nervous system. A Mexican 25-year-old male patient presented for diagnosis of multiple radiolucent lesions observed on routine radiographic examination. General aspects revealed cognitive delay, eye alterations, and kidney involvement, which support the diagnosis of LS. Radiolucent well-delimited lesions were observed in both mandibular angle and symphysis. Under general anesthesia, incisional biopsy and decompression were performed. Histological aspects led to diagnosing odontogenic keratocyst (OKC) for all lesions. The lesions in the right and left mandibular angles were decompressed, and the symphyseal lesion was enucleated. A 2-month follow-up shows the bone healing process. There are few reports detailing oral findings in LS. Here, we reported the first case of multiple OKC in a patient with LS. In addition, we performed a literature review on odontogenic lesions in patients affected by LS.
Topics: Male; Humans; Adult; Oculocerebrorenal Syndrome; Odontogenic Cysts; Odontogenic Tumors; Mandible; Diagnosis, Differential
PubMed: 37891120
DOI: 10.1016/j.oooo.2023.07.008 -
Prenatal Diagnosis May 2024Oculocerebrorenal syndrome (Lowe syndrome) is a rare X-linked disorder affecting 1/500,000 males that most frequently affects the eyes, central nervous system, and...
Oculocerebrorenal syndrome (Lowe syndrome) is a rare X-linked disorder affecting 1/500,000 males that most frequently affects the eyes, central nervous system, and kidneys. Phenotypic presentation includes congenital cataracts, developmental delay, intellectual disability, and Fanconi-type renal dysfunction. Lowe Syndrome is caused by hemizygous loss of function variants in the OCRL gene. While individuals may live into the third and fourth decade of life, some will die in the first few years of either renal failure or infection. While early diagnosis is important, few cases have documented the prenatal phenotype of this condition, which has included bilateral cataracts and variable neurological abnormalities. We report a case of a family with an extensive history of congenital cataracts, immune compromise, and neonatal death in male members. The fetus was found to have a unilateral cataract, mild ventriculomegaly, vertebral anomalies, and an underlying diagnosis of Lowe Syndrome with a mutation in OCRL at c.2582-1G>C (IVS23-1G>C).
Topics: Humans; Oculocerebrorenal Syndrome; Female; Male; Phenotype; Pregnancy; Cataract; Adult; Phosphoric Monoester Hydrolases; Prenatal Diagnosis; Infant, Newborn
PubMed: 38554254
DOI: 10.1002/pd.6563 -
Cell Communication and Signaling : CCS Dec 2023This study aimed to identify an orcl1 mutation in a patient with Dent-2 Disease and investigate the underlying mechanisms.
BACKGROUND
This study aimed to identify an orcl1 mutation in a patient with Dent-2 Disease and investigate the underlying mechanisms.
METHODS
The ocrl1 mutation was identified through exome sequencing. Knockdown of orcl1 and overexpression of the orcl1 mutant were performed in HK-2 and MPC5 cells to study its function, while flow cytometry measured reactive oxygen species (ROS), phosphatidylserine levels, and cell apoptosis. Scanning electron microscopy observed crystal adhesion, while transmission electron microscopy examined kidney tissue pathology. Laser scanning confocal microscopy was used to examine endocytosis, and immunohistochemical and immunofluorescence assays detected protein expression. Additionally, podocyte-specific orcl1 knockout mice were generated to investigate the role of orcl1 in vivo.
RESULTS
We identified a mutation resulting in the replacement of Histidine with Arginine at position 318 (R318H) in ocrl1 in the proband. orcl1 was widely expressed in the kidney. In vitro experiments showed that knockdown of orcl1 and overexpression of ocrl1 mutant increased ROS, phosphatidylserine exocytosis, crystal adhesion, and cell apoptosis in HK-2 cells. Knockdown of orcl1 in podocytes reduced endocytosis and disrupted the cell cycle while increasing cell migration. In vivo studies in mice showed that conditional deletion of orcl1 in podocytes caused glomerular dysfunction, including proteinuria and fibrosis.
CONCLUSION
This study identified an R318H mutation in orcl1 in a patient with Dent-2 Disease. This mutation may contribute to renal injury by promoting ROS production and inducing cell apoptosis in tubular cells, while disrupting endocytosis and the cell cycle, and promoting cell migration of podocytes. Video Abstract.
Topics: Humans; Animals; Mice; Podocytes; Reactive Oxygen Species; Phosphatidylserines; Oculocerebrorenal Syndrome; Endocytosis; Apoptosis; Cell Cycle
PubMed: 38049819
DOI: 10.1186/s12964-023-01272-4 -
Children (Basel, Switzerland) Jul 2023Löwe syndrome (the oculocerebrorenal syndrome of Löwe, OCRL, OMIM #309000, ORPHA: 534) is a very rare multisystem X-linked disorder characterized by ocular, kidney and...
OBJECTIVES
Löwe syndrome (the oculocerebrorenal syndrome of Löwe, OCRL, OMIM #309000, ORPHA: 534) is a very rare multisystem X-linked disorder characterized by ocular, kidney and nervous system anomalies.
CASE PRESENTATION
We present the first Bulgarian genetically confirmed patient with OCRL. The patient had facial dysmorphism, cryptorchidism, congenital cataracts, nystagmus, delayed physical and mental development, and poor nutritional status. He had severe rickets, metabolic acidosis, hypokalaemia, hypophosphataemia, and low IGF-1 levels at the age of three, in addition to his developmental delay. The molecular-genetic analysis reported a pathogenic variant c.1124A>G, p.H375R in the gene. This variant was inherited from the mother, who was a carrier. Following the diagnosis of OCRL, treatment with potassium citrate, phosphate, and calcitriol was initiated, along with an increase in caloric intake. Following general physical and biochemical improvement, therapy with rhGH started 4 years ago, and current results are presented.
CONCLUSIONS
The patient with Löwe syndrome who was presented with a 6-year follow-up demonstrates the complexity of rare disease cases and the value of multidisciplinary care together with growth hormone treatment for better results in these patients.
PubMed: 37508663
DOI: 10.3390/children10071166