<scp><i>SCYL1</i></scp> disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of <scp><i>SCYL1</i></scp>

McNiven, Vanda; Gattini, Daniela; Siddiqui, Iram; Pelletier, S. William; Brill, Herbert; Avitzur, Yaron; Mercimek‐Andrews, Saadet

doi:10.1002/ajmg.a.62079

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…2 Up to date, successful liver transplantation was reported in three patients without any hepatic crises after transplantation. 2,10 Our patient displayed gait abnormalities at the age of 22 months.…”

Section: Discussionmentioning

confidence: 72%

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SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation

Warasnhe,

Özçay,

Kılıç

et al. 2023

Pediatric Transplantation

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BackgroundPediatric acute liver failure (PALF) with undetermined etiology is associated with higher liver transplantation and lower spontaneous recovery (transplant‐free) rates. The diagnostic odyssey in PALF cases hinders appropriate management and follow‐up after liver transplantation. Advances in whole exome sequencing analysis have already been successful at identifying new genetic causes of PALF.Case PresentationWe report a 17‐year‐old girl who underwent liver transplantation at the age of 7 months due to acute liver failure and presented later with abnormal neurological manifestations, that is, gait disturbances, dysarthria, and mental retardation that led us to the diagnosis of SCYL1 deficiency.ConclusionPALF cases should be screened for possible underlying genetic disorders. Genetic studies and reanalysis of whole‐genome sequencing data may help identify new cases and clarify the genotype–phenotype correlation. SCYL1 deficiency should be suspected in PALF patients who develop neurological involvement after LT. Early diagnosis is vital for proper management of ALF crises in SCYL1 deficiency patients. Despite the reported favorable outcomes of ALF crises in SCYL1 deficiency, liver transplantation decision should be discussed on a case‐by‐case basis.

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Section: Discussionmentioning

confidence: 72%

“…Previously reported ALF crisis outcomes in patients with SCYL1 deficiency are generally favorable with spontaneous resolution nearly at the age of 4 years 2 . Up to date, successful liver transplantation was reported in three patients without any hepatic crises after transplantation 2,10 …”

Section: Discussionmentioning

confidence: 93%

SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation

Warasnhe,

Özçay,

Kılıç

et al. 2023

Pediatric Transplantation

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“…Most patients' liver episodes decline or cease in early childhood. Three of 18 patients have been reported to undergo liver transplantation at 23 months of age [ 1 ], 7 months [ 4 ], and 21 months [ 4 ] ( Table 1 ). However, none of the cases were expected to have SCYL1 mutation at the time of transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical fndings encompass recurrent episodes of PALF/low GGT cholestasis, cerebellar atrophy, ataxia, peripheral neuropathy, short stature, scoliosis, and hip dysplasia. Until now, three cases of liver transplantation have been identifed [1,4] (Table 1) among 18 patients with SCYL1 mutation reported [1][2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

CALFAN (Low γ-Glutamyl Transpeptidase (GGT) Cholestasis, Acute Liver Failure, and Neurodegeneration) Syndrome: A Case Report with 3-Year Follow-Up after Liver Transplantation in Early Adulthood

Youssef,

Mascia,

McGuire

et al. 2023

Case Reports in Hepatology

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CALFAN syndrome is an extremely rare disease consisting of recurrent pediatric acute liver failure (PALF), neurodegenerative diseases, and skeletal abnormalities associated with SCYL1 gene mutation. To date, three of 18 patients reported underwent liver transplantation in infancy and early childhood (7–23 months). Here, we report a case of CALFAN syndrome with infantile onset, recurrent jaundice/PALF requiring liver transplantation in early adulthood. At the most recent follow-up, 3 years after transplantation, the patient is doing well.

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Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency

Peters,

Dattner,

Schlieben

et al. 2024

J of Inher Metab Disea

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Among genetic disorders of vesicular trafficking, there are three causing recurrent acute liver failure (RALF): NBAS, RINT1, and SCYL1‐associated disease. These three disorders are characterized by liver crises triggered by febrile infections and account for a relevant proportion of RALF causes. While the frequency and severity of liver crises in NBAS and RINT1‐associated disease decrease with age, patients with SCYL1 variants present with a progressive, cholestatic course. In all three diseases, there is a multisystemic, partially overlapping phenotype with variable expression, including liver, skeletal, and nervous systems, all organ systems with high secretory activity. There are no specific biomarkers for these diseases, and whole exome sequencing should be performed in patients with RALF of unknown etiology. NBAS, SCYL1, and RINT1 are involved in antegrade and retrograde vesicular trafficking. Pathomechanisms remain unclarified, but there is evidence of a decrease in concentration and stability of the protein primarily affected by the respective gene defect and its interaction partners, potentially causing impairment of vesicular transport. The impairment of protein secretion by compromised antegrade transport provides a possible explanation for different organ manifestations such as bone alteration due to lack of collagens or diabetes mellitus when insulin secretion is affected. Dysfunction of retrograde transport impairs membrane recycling and autophagy. The impairment of vesicular trafficking results in increased endoplasmic reticulum stress, which, in hepatocytes, can progress to hepatocytolysis. While there is no curative therapy, an early and consequent implementation of an emergency protocol seems crucial for optimal therapeutic management.

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SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1

Cited by 5 publications

References 13 publications

SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation

SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation

CALFAN (Low γ-Glutamyl Transpeptidase (GGT) Cholestasis, Acute Liver Failure, and Neurodegeneration) Syndrome: A Case Report with 3-Year Follow-Up after Liver Transplantation in Early Adulthood

Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency

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