Intestinal failure and transplantation in microvillous inclusion disease

Caamaño, B. Fernández; Blanco, María José; Tomé, L. Fernández; Lizaldez, E Burgos; Osés, J. Sarría; Arias, Manuel Molina; Bozano, Gerardo Prieto

doi:10.1016/j.anpede.2015.08.001

Cited by 4 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, in other patients with MVID and MYO5B mutations and presenting with CLD no mislocalization of these canalicular transporters was reported, and CLD later resolved. ( 23 ) In another patient without MVID diagnosed with CLD and MYO5B mutations no mislocalization of BSEP was observed. ( 7 ) Furthermore, 5 patients with MVID showed reduction of cholestasis and pruritus when soybean oil–based lipids in the TPN were replaced by fish oil–based lipids, indicating TPN as a contributing factor in cholestasis and pruritus in at least these patients with MVID.…”

Section: Myosin 5b–associated Cholestatic Liver Diseasementioning

confidence: 99%

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low‐Gamma‐Glutamyltransferase Cholestasis

IJzendoorn

Qiu

et al. 2020

Hepatology

View full text Add to dashboard Cite

Myosin 5B-Associated Cholestatic Liver Disease Cholestatic liver disease (CLD) is characterized by an increase in the serum concentrations of compounds that are normally excreted with bile, such as bile acids and bilirubin. (1) CLD clinically manifest with cholestasis, jaundice, and pruritis. Diagnosis involves evaluation of the patient's clinical manifestations, exclusion of common causes of childhood cholestasis, and analyses of blood biochemistry and liver histology. (1) One blood marker that aids in the differential diagnosis of liver diseases is gamma-glutamyltransferase (GGT), a liver enzyme which is typically elevated in serum upon liver damage. The best known CLDs characterized by low/normal GGT are the benign recurrent and progressive forms of familial intrahepatic cholestasis (BRIC/PFIC), which are caused by mutations in the adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) gene encoding the ATP8B1 protein (BRIC/PFIC1) or in the adenosine triphosphate-binding cassette family B member 11 (ABCB11) gene encoding the canalicular bile salt export pump (BSEP) (BRIC/PFIC2). (2,3) In hepatocytes, ATP8B1 and BSEP are localized to the apical bile canalicular domain, where they contribute to biliary secretion. When mutated as in PFIC1/2 patients, the respective proteins are less expressed or mislocalized and/or display impaired activity, leading to defective biliary secretion and, consequently, cholestasis. (2,3) Since 2017 four independent reports have identified in total 30 different myosin 5B (MYO5B) mutations in 22 patients with non-microvillus inclusion disease (MVID) who were diagnosed with intermittent, recurrent, or progressive cholestasis presenting with jaundice, pruritus, hepatomegaly, and low/normal serum levels of GGT (Fig. 1; Supporting Table S1). These patients tested negative for mutations in other PFIC-associated genes. (4-7) MYO5B mutations may account for approximately 20% of pediatric patients with idiopathic low-GGT intrahepatic cholestasis. (8)

show abstract

Section: Myosin 5b–associated Cholestatic Liver Diseasementioning

confidence: 99%

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low‐Gamma‐Glutamyltransferase Cholestasis

IJzendoorn

Qiu

et al. 2020

Hepatology

View full text Add to dashboard Cite

show abstract

“…Seven patients in the combined group (with available GGT activity) showed normal/low‐GGT cholestasis: 6 of them carried at least one non‐null variant; one patient (Table , A1‐P6) carried the so‐called biallelic “null” variants. Though we cannot confirm the expression of the MYO5B because no liver material from that patient was available, one of the stop‐gain variants c.5383C>T (p. Arg1795*) located in the less than 50 nucleotides upstream of the last exon‐exon junction, which was predicted to produce a truncated protein with preserved RAB11A‐binding site, rather than triggering nonsense‐mediated mRNA decay (NMD) like the real null mutant 22,23 . This evidence further supports that a non‐null variant that preserves the RAB11A‐binding site is essential for the “RAB11A‐mediated gain‐of‐toxicity” theory for MYO5B ‐associated cholestasis, even in the patients with combined intestine and liver involvement.…”

Section: Discussionmentioning

confidence: 86%

MYO5B‐associated diseases: Novel liver‐related variants and genotype‐phenotype correlation

Wang

Qiu

et al. 2021

Liver International

View full text Add to dashboard Cite

Background & Aims Biallelic pathogenic variants in MYO5B cause microvillus inclusion disease (MVID), or familial intrahepatic cholestasis (FIC). The reported FIC patients are scarce and so the genotype‐phenotype correlation has not been fully characterised. This study aimed to report more MYO5B‐associated FIC patients and correlate genotypes to phenotypes in more detail. Methods The phenotype and genetic data of 12 newly diagnosed MYO5B‐associated (including 11 FIC) patients, as well as 118 previously reported patients with available genotypes, were summarised. Only patients with biallelic MYO5B variants were enrolled. Nonsense, frameshift, canonical splice sites, initiation codon loss, and single exon or multiexon deletion were defined as null MYO5B variants. Results Phenotypically, 50 were isolated MVID, 47 involved both liver and intestine (combined), and 33 were isolated FIC (9 persistent, 15 recurrent, 3 transient, and 6 un‐sub‐classified) patients. The severity of intestinal manifestation was positively correlated to an increased number of null variants (ρ = 0.299, P = .001). All FIC patients carried at least one non‐null variant, and the severity of cholestasis was correlated to the presence of a null variant (ρ = 0.420, P = .029). The proportion of FIC patients (16/29, 55%) harbouring missense/in‐frame variants affecting the non‐motor regions of MYO5B was significantly higher than that of MVID (3/25, 12%, P = .001) and combined patients (3/31, 10%, P = .000). 10 of the 29 FIC patients harboured missense/in‐frame variants at the IQ motifs comparing to none in the 56 MVID and combined patients (P = .000). Conclusions The phenotype of MYO5B deficiency was associated with MYO5B genotypes, the nullity or the domain affected.

show abstract

“…There is no medical treatment capable of overcoming the intestinal failure, with the mainstay of treatment centered around parenteral support and decreasing the risk of associated comorbid conditions. Surgically, intestinal transplantation has shown promise [ 115 , [118] , [119] , [120] ], and subtotal enterectomy as a means to better control bowel losses or as a bridge to transplantation has been recently described [ 121 ].…”

Section: Diet-induced Diarrheasmentioning

confidence: 99%

Diet management in congenital diarrheas and enteropathies – general concepts and disease-specific approach, a narrative review

Avitzur,

Jimenez,

Martincevic

et al. 2024

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

Intestinal failure and transplantation in microvillous inclusion disease

Cited by 4 publications

References 34 publications

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low‐Gamma‐Glutamyltransferase Cholestasis

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low‐Gamma‐Glutamyltransferase Cholestasis

MYO5B‐associated diseases: Novel liver‐related variants and genotype‐phenotype correlation

Diet management in congenital diarrheas and enteropathies – general concepts and disease-specific approach, a narrative review

Contact Info

Product

Resources

About