New MYO5B gene mutation detected in man with PFIC type 10
Standard cholestasis treatment, traditional Chinese medicine resolve condition
A combination of two mutations in the MYO5B gene, including one that has not been previously reported, was the likely cause of a mild form of progressive familial intrahepatic cholestasis type 10 (PFIC10) in a 36-year-old man, a case report showed.
His condition totally resolved only after a combined regimen of standard cholestasis treatment and traditional Chinese medicine.
“Our findings contribute to the understanding of MYO5B pathogenic [disease-causing] variants, facilitating prompt genetic diagnosis, family counseling, and prenatal testing opportunities,” researchers wrote.
The study, “Case Report: A rare case of familial progressive cholestasis type 10 in an adult with heterozygous MYO5B variant,” was published in Frontiers in Gastroenterology.
PFIC diagnosis can be challenging
PFIC is a group of rare genetic liver diseases marked by problems in the production and/or secretion of the digestive fluid bile from liver cells. This makes it more difficult for bile to flow out of the liver and into the intestines.
This stalled bile flow, called cholestasis, can cause bile to build up to toxic levels within the liver, damaging the organ. Bile can also leak into the bloodstream, leading to symptoms such as itching and jaundice, or yellowing of the skin and whites of the eyes.
PFIC typically manifests in infancy and “progresses rapidly, often leading to liver failure,” the researchers wrote. However, symptoms may vary from person to person and some cases may not manifest until adulthood.
“Due to the clinical [variability] of PFIC, diagnosis is often challenging, and genetic testing is recommended to identify pathogenic variants,” the researchers wrote.
Different genetic mutations at the root of PFIC are linked to different disease types. PFIC10 is mainly caused by mutations in both copies of the MYO5B gene, which codes for a protein called myosin Vb, that is key for the localization of proteins involved in bile formation and secretion.
Liver biopsy reveals cholestasis
In this report, a team of researchers in China described the case of a 36-year-old man who carried two distinct MYO5B mutations — one previously unknown — that were the likely cause of his delayed-onset PFIC10.
The man was admitted to the researchers’ hospital due to jaundice and itching that had started two months prior.
He initially experienced fever and chills, which resolved with oral treatment at a local clinic. Three days later, however, he began to experience a new bout of symptoms including jaundice, itchy skin, dark urine, and diarrhea.
Initial blood work showed elevated levels of several liver enzymes, which may indicate liver damage. High blood levels of bilirubin, a yellowish molecule found in bile, also suggested the liver was not properly processing bile.
Subsequent testing at another hospital showed further increases in these markers.
At the researchers’ hospital, the man underwent comprehensive testing, including analysis of a liver biopsy, which showed mild chronic inflammation, cholestasis, and some structural changes.
“After excluding common causes of liver injury including viral infections, autoimmune diseases, alcoholic liver disease, and drug-induced [liver damage], liver biopsy revealed … cholestasis,” the team wrote.
Man found to carry different mutation in both copies of MYO5B gene
Because the blood levels of a specific liver enzyme, gamma-glutamyl transferase, were within the normal range, contrary to the other main liver enzymes, the clinicians suspected an inherited metabolic liver disorder, and comprehensive genetic testing was ordered.
The man was found to carry a different mutation in both copies of the MYO5B gene: a previously known mutation called c.1165G>T and a new mutation called c.3604-1G>C.
The known mutation, resulting in a change in a single amino acid — protein’s building block — was predicted to likely affect protein function. The newly identified variant, classified as a splicing mutation, was predicted to be likely disease-causing. Splicing mutations can change the length and sequence of the resulting protein. These findings led to a diagnosis of PFIC10.
The man initially received several medications to protect his liver, ease cholestasis, control inflammation, and reduce itchiness and jaundice. This included ursodeoxycholic acid (UDCA), a first-line treatment for cholestasis.
This favorable outcome suggests that the identified MYO5B variants may represent a previously unrecognized genetic cause of cholestatic liver disease with potential treatment responsiveness.
He was discharged, but showed signs of recurrently high bilirubin levels that required readmission. A second treatment regimen included UDCA and some other medications from the first round of treatment, along with traditional Chinese medicine.
“The incorporation of traditional Chinese medicine with conventional therapy resulted in complete symptom resolution and biochemical normalization during follow-up,” the researchers wrote.
The man’s jaundice and itchy skin resolved entirely, and his bilirubin levels normalized. He also showed reductions in the levels of liver enzymes.
“This favorable outcome suggests that the identified MYO5B variants may represent a previously unrecognized genetic cause of cholestatic liver disease with potential treatment responsiveness,” the team wrote.
This case also highlights how “a comprehensive diagnostic approach combining clinical evaluation, metabolic screening, and genetic testing is crucial for accurate diagnosis,” the researchers concluded.
