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The ‘molar tooth sign’ is typically a neuroimaging finding, while nephronophytosis (NPH) or cystic dysplasia, retinal degeneration, aplasia, and/or cerebellar vermis hypoplasia are some of the manifestations of multi-organ involvement.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Renal involvement typically arises in childhood or young adulthood and leads to end-stage renal disease (ESRD) in a minority of cases.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Here, we present the case of a 41-year-old female who initially developed renal and respiratory failure. Our report outlines the exceptionally late onset of ESRD in older individuals with JS and underscores the significance of early detection.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 41-year-old female patient, undergoing maintenance hemodialysis treatment three times a week for five years, was admitted to the intensive care unit following respiratory arrest due to aspiration. After extubation, she was transferred to the nephrology clinic. The cause of her ESRD remained unknown. She had been diagnosed with hypertension three years prior and had been prescribed valsartan and amlodipine. Her parents did not have any additional health issues aside from hypertension and cerebral palsy. The patient exhibited mental retardation and was non-verbal, displaying generalized hypotonia. She showed prominent oculomotor apraxia and rotatory nystagmus, especially in lateral gaze, although a detailed eye examination was not feasible due to her lack of cooperation. She had experienced apnea–hyperpnea attacks since the neonatal period, and considering her current developmental delay, it was attributed to cerebral palsy. Vital signs were stable, except for elevated blood pressure at 180/100<span class="elsevierStyleHsp" style=""></span>mmHg. Biochemical profile showed anaemia (haemoglobin 8.0<span class="elsevierStyleHsp" style=""></span>g/dL (reference range 11.7–15.5)) and renal dysfunction (blood urea nitrogen 95<span class="elsevierStyleHsp" style=""></span>mg/dL (reference range 17–43), serum creatinine 5.32<span class="elsevierStyleHsp" style=""></span>mg/dL (reference range 0.66–1.09)). Brain computer tomography revealed the characteristic ‘molar tooth sign’ at the lower peduncles of the cerebellum (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Renal ultrasonography indicated reduced kidney sizes and parenchymal thickness, featuring hyperechoic kidneys containing multiple cortical cysts with thin septa. Based on the patient's neurological examination, brain tomography, renal ultrasonography, and laboratory findings, a diagnosis of JS was made. Her elevated blood pressure in the intensive care unit was attributed to excessive fluid administration and normalized with diuretic treatment. Unfortunately, the patient has died from sepsis approximately 2.5 years after discharge.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">JS and related disorders generally fall into six categories: pure JS, JS plus ocular defects, JS plus renal defects, JS plus oculo-renal defects, JS plus hepatic defects, and JS plus orofacio-digital defects.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Renal findings in JS exhibit considerable variability. In a series of 97 patients, renal involvement was noted in 30% of cases (NPH; 20%, unspecified cystic kidney disease; 7%, unilateral cystic dysplastic kidneys; 3%), with most cases being detected via ultrasonography. NPH represents the most common renal pathology in these circumstances.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The genes primarily affected in JS with renal defects are CEP290, RPGRIP1L, and TMEM67.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Unfortunately, due to limitations in our hospital's facilities, genetic testing was not performed for the index case or her relatives.</p><p id="par0020" class="elsevierStylePara elsevierViewall">ESRD in JS is a serious and insidious complication of renal disease, often overshadowed by the neurological issues in patients. Renal disease can go unnoticed for an extended period, typically diagnosed when kidney function is already impaired and complications have arisen. These complications, such as anemia and growth retardation, are only partially reversible. Furthermore, late diagnosis accelerates the progression toward renal failure.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> In a prospective study by Fleming et al., the average age of ESRD onset in patients with JS was 11.3 years, which is noteworthy.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Regardless of exact prevalence, early detection of renal injury is crucial for both children and adults at risk of adverse renal outcomes.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Urine osmolality<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and neutrophil gelatinase-associated lipocalin<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> are recognized as early indicators of renal injury in JS. Using these markers to detect renal damage early may help prevent the progression to ESRD, thereby reducing mortality and morbidity rates. In cases of unexplained renal failure with neurological findings, it is essential to consider JS and related conditions in the differential diagnosis, as in our case. Our patient commenced maintenance hemodialysis at the age of 36, which is relatively advanced for JS, and received her diagnosis at approximately 41 years of age. The delayed diagnosis contributed to a delay in preventing the mortality and morbidity associated with ESRD and its complications.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The earlier we diagnose JS and related disorders, the more awareness we can raise about the syndrome and its associated conditions, making it easier to prevent complications, such as renal failure, before they progress to end-stage disease. Therefore, early detection of structural or functional renal damage, along with prompt intervention and comprehensive complication assessment, can delay the need for renal transplantation or dialysis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Informed consent</span><p id="par0035" class="elsevierStylePara elsevierViewall">Verbal informed consent was obtained from the patient who agreed to take part in the study.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authorship</span><p id="par0040" class="elsevierStylePara elsevierViewall">Each Author has contributed substantially to the research, preparation and production of the paper and approves of its submission to the Journal.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">No conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Informed consent" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authorship" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1869 "Ancho" => 1600 "Tamanyo" => 210249 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cerebellar atrophy, deformation of the fourth ventricle and elongation of the superior cerebellar peduncles characterised by ‘molar tooth’ appearance on brain computer tomography.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Joubert syndrome (and related disorders) (OMIM 213300)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Parisi" 1 => "D. Doherty" 2 => "P.F. Chance" 3 => "I.A. Glass" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ejhg.5201648" "Revista" => array:6 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2007" "volumen" => "15" "paginaInicial" => "511" "paginaFinal" => "521" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17377524" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective evaluation of kidney disease in Joubert syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.R. Fleming" 1 => "D.A. Doherty" 2 => "M.A. Parisi" 3 => "I.A. Glass" 4 => "J. Bryant" 5 => "R. Fischer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.05660517" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2017" "volumen" => "12" "paginaInicial" => "1962" "paginaFinal" => "1973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29146704" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impaired urinary concentration ability is a sensitive predictor of renal disease progression in Joubert syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Nuovo" 1 => "L. Fuiano" 2 => "A. Micalizzi" 3 => "R. Battini" 4 => "E. Bertini" 5 => "R. Borgatti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfy333" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2020" "volumen" => "35" "paginaInicial" => "1195" "paginaFinal" => "1202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30403813" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Joubert syndrome diagnosed renally late" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Collard" 1 => "C. Byrne" 2 => "M. Georgiou" 3 => "M. Michaelides" 4 => "A. Dixit" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ckj/sfaa007" "Revista" => array:6 [ "tituloSerie" => "Clin Kidney J" "fecha" => "2020" "volumen" => "14" "paginaInicial" => "1017" "paginaFinal" => "1019" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33777383" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NGAL as an early biomarker of kidney disease in Joubert syndrome: three brothers compared" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Lacquaniti" 1 => "V. Chirico" 2 => "V. Donato" 3 => "S. Briuglia" 4 => "V. Cernaro" 5 => "R. Gallizzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/0886022X.2011.649677" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2012" "volumen" => "34" "paginaInicial" => "495" "paginaFinal" => "498" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22260509" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016200000007/v2_202405192235/S2387020624001001/v2_202405192235/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016200000007/v2_202405192235/S2387020624001001/v2_202405192235/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624001001?idApp=UINPBA00004N" ]