Central Journal of Liver and Clinical Research Case Report *Corresponding author Daniel D. Mais, Department of Pathology, University of Texas Health, 7703 Floyd Curl Dr, San Antonio, TX 78229, Clinicopathologic Features of USA, Tel: 210-863-2646; Fax: 210-567-6729; Email: Submitted: 09 September 2017 Hepatic Involvement in Senior- Accepted: 08 October 2017 Published: 10 October 2017 Loken Syndrome: A Case Report ISSN: 2379-0830 Copyright and Review of Literature © 2017 Mais et al. OPEN ACCESS Lian-Qun Qiu and Daniel D. Mais* Department of Pathology, University of Texas Health, USA Keywords • Senior-loken syndrome • Congenital hepatic fibrosis Abstract • Retinopathy Senior-Loken syndrome is an autosomal recessive disorder, characterized by the • Nephronophthisis combination of nephronophthisis and retinopathy, the hepatic manifestations of which have not been well characterized. We describe here a case of a 14-year-old girl with Senior- Loken syndrome who presented with persistent elevation of liver enzymes. Histological examination of liver biopsy specimen revealed remarkable portal expansion featured by portal fibrosis and minute ductile duplication, consistent with the malformation of interlobular bile ducts. The liver parenchyma and lobular architecture were relatively preserved with minimal inflammation. The clinical and morphologic features for the triad of nephronophthisis, retinopathy, and congenital hepatic fibrosis were reviewed and compared with other cases available in the literature. We presented a case of Senior- Loken syndrome with severe nephronophthisis and mild retinal degeneration in association with congenital hepatic fibrosis. The liver involvement poses a big challenge to the clinical interventions after renal transplantation. ABBREVIATIONS The retinal lesions in the Senior-Loken syndrome are variable, ranging from Leber’samaurosis to retinitis pigmentosa. ALP: Alkaline Phosphatase; ALT: Alanine Aminotransferase; This condition causes vision problems, including an increased AST: Aspartate Aminotransferase sensitivity to light (photophobia), involuntary movements INTRODUCTION of the eyes (nystagmus), and extreme farsightedness (hyperopia). Retinitis pigmentosa is characterized by bone Senior-Løken syndrome is a rare autosome recessive spicule pigmentation of the retina and presents initially with disorder, characterized by the combination of nephronophthisis night blindness which slowly progress to daytime blindness. Leber’samaurosis is a severe form of retinal dystrophy which of life. The estimated prevalence is about 1 in 1 million people leads to blindness nystagmus and a diffuse atypical retinal and retinopathy, which usually presents in the first two decades et al., and Loken et al. [1,2], and has also been referred to as that have been reported in this syndrome include cataract, Coat’s hereditaryworldwide. renal-retinalIt was first described syndrome, in 1961,juvenile separately nephronophthisis by Senior pigmentation and pallor of the optic disc [7]. Other ocular findings with leberamaurosis, and renal dysplasia with retinal aplasia. Hepatic manifestations of Senior-Loken syndrome have been diseaseLiver and involvement keratoconus in [8,9]. Senior-Loken syndrome has been mentioned in a small number of reports. reported rarely, but the clinicopathologic features are not well characterized. The present case reports was aimed at describing Nephronophthisis presents initially with polyuria and the clinical and morphologic features in a recent case of polydipsia and progressing insidiously to end-stage renal disease Senior-Loken syndrome and, in conjunction with prior reports, summarizes the known features of liver involvement in this syndrome. theby the tubular second basement decade. Themembrane main histological [3,4]. It is findings the most are common tubular atrophy, interstitial fibrosis, and thickening and lamellation of CASE PRESENTATION presenting alone or in combination with another multisystem A 14-year-old female patient was referred to the pediatric disorder,genetic cause and ofSenior-Loken end stage renal syndrome disease accounts in the first for three about decades, 10-15 hepatology division for the evaluation of persistent elevation of % of cases [5-7]. liver enzymes with intermittent itching in the soles of the feet. Cite this article: Qiu LQ, Mais DD (2017) Clinicopathologic Features of Hepatic Involvement in Senior-Loken Syndrome: A Case Report and Review of Litera- ture. J Liver Clin Res 4(2): 1037. Mais et al. (2017) Email: Central She was asymptomatic overall, denying jaundice, icterus, disease secondary to nephronophthisis, and decreased night dark urine, fatigue, and malaise. Her family history was non- visionHer past due medical to retinitis history pigmentosa, was significant with a diagnosisfor end-stage of Senior- renal contributory. She was progressing normally in school. In early Loken syndrome type 1, with NPHP1 gene mutation, rendered in 2014. She subsequently underwent hemodialysis followed by 12 years of age, an ultrasound at that time was interpreted peritoneal dialysis, and cadaveric renal transplantation in July as2014 cirrhosis, when sheand firsta liver presented biopsy forwas end-stage performed. renal She diseasewas then at 2015. noted to have abnormal liver enzymes and alkaline phosphatase (ALP), with alanine aminotransferase (ALT) and aspartate Table 1: Age at Liver Clinical and morphologicalRetinal features of the triad of nephronophthisis, retinal lesion and congenital hepatic fibrosis. Case Sex diagnosis Hepatomegaly function Liver biopsy Other Follow-up Reference lesions (years) tests Diffuse Mild peri-lobular Tapetoretinal elevation Mental Died of uremia at 1 M 12 Y degeneration ALP: retardation age 13 bile duct normal fibrosis,proliferation small [6] Mental Tapetoretinal Minimal retardation, Died of uremia at 2 M 12 degeneration Y [23] elevation psychomotor (since birth) Portal fibrosis retardation Not able to Growth age 19 follow light retardation, Died of uremia at 3 M 4.5 and blindness Y Normal ductal polydactyly [25] age 5 within 4 years Portalproliferation fibrosis, and cerebral of age abnormalities Not able to Growth follow light AST 54 ductal retardation, Died of uremia at 4 M 5.5 and blindness Y Portalproliferation, fibrosis, [25] thymic atrophy, age 5.75 within 4 years ALP 240 centri-lobular ptosis of age ALT 65 congestion Liver failure 2 years later after kidney Pigmentary ALT 70 5 F 15 Y (not biopsy- transplantation and [24] retinopathy ALP 300 Liverproven) fibrosis cyclophosphamide therapy Fibrosis, Pigmentary ALT 53 portal A minor increase retinopathy ALP 222 F 13 Y in liver enzymes in [24] (night the rest: proliferation 4-year follow-up blindness) normal 6 ofinfiltration, bile ducts Mental retardation, Retinitis coloboma, 7 F 12.5 Y NA NA [5] pigmentosa skeletal Portal fibrosis anomalies, and cerebellar ataxia Mental retardation, kyphoscoliosis, Retinitis short 8 F 13 NA NA (not biopsy- NA [5] pigmentosa metatarsale IV), Liverproven) fibrosis cerebellar ataxia, pulmonary emphysema ALT:144- Retinitis 770 Ductal pigmentosa Hepato- AST: 37- F 12 proliferation, Current This report (decreased splenomegaly 300 9 night vision) 851 portal fibrosis ALP: 97- Notes: Abbreviations: ALT: Alanine Transaminase; AST: Aspartate Transaminase; ALP: Alkaline Phosphatase Case 2, mother had abnormal ERG; Cases 3 and 4 were monozygotic twins; Cases 5 and 6 were sisters from one family; NA, not available. J Liver Clin Res 4(2): 1037 (2017) 2/5 Mais et al. (2017) Email: Central aminotransferase (AST) being elevated to 1.5 to 2 times the nephronophthisis and retinopathy. Also reported are several variants, including some with short stature, kyphoscoliosis, small hands (short metacarpals), madarosis, dysmorphic features enzymesupper limit surged, of normal with inALT late of 2014. approximately Her liver enzymes 500 U/L, fluctuated AST 200 U/L,between and normalALP 800 to U/L. slightly Her serumelevated bilirubin until earlyand albumin2016 when had Cases in which there is hepatic involvement are rare and the remained normal throughout the course. clinicopathologicof face and hands, features pancreatitis, in such and caseshepatic therefore fibrosis [5,10-13].not well characterized. On examination, she was found to have short stature and underweight (< 5th percentile for age) before renal transplantation Senior-Loken syndrome, like nephronophthisis disorders in 2015 but had gained weight normally since, achieving normal generally, is considered one of the “ciliopathies,” multisystem developmental disorders stemming from defects in genes encoding ciliary proteins [4,14]. Mutations in NPHP2 and NPHP3 toranges have inhepatomegaly August 2016. and Her splenomegaly. eye examination There showed were no no stigmata icterus genes in particular, although only accounting for 1% of all cases ofor portalnystagmus hypertension, and negative and pupillaryupper endoscopy reflexes. showedShe was noalso varices. found of nephronophthisis overall, are prevalent among patients NPHP2-encoded protein Her laboratory studies were remarkable for pancytopenia, inversin interacts with nephrocystin-1, the product of NPHP1, particularly low platelet count, which were largely ascribed andwith togetherliver involvement these co-localize [4,15,16]. to Thecilia within the developing to hypersplenism after bone marrow biopsy to rule out NPHP3 encodes nephrocystin-3, which interacts hematological disorders in January 2014. Her transplanted renal with nephrocystin-1 and inversin and can inhibit