ABCB4 gene mutation-associated cirrhosis with systemic amyloidosis:A case report

BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.

A case of systemic amyloidosis beginning with purpura

Primary systemic amyloidosis is a relatively rare disease, caused when abnormal extracellular deposition of fibrillary protein builds up in a variety of target organs, such as heart, kidneys, lungs liver, and so forth. The symptoms of the disease are usually vague, while many kinds of auxiliary or laboratory examinations especially pathologic biopsy can provide a clue for the diagnosis. Here we described a case who had purpura-like lesions in the initial stage, followed by progressive malfunctions in the kidneys, the heart, the lungs, as wel~ as the liver. The final diagnosis was primary systemic amyloidosis determined by skin pathologic biopsy. And the disease led to a fatal outcome within three months after the diagnosis.

Primary Systemic Amyloidosis Presenting as Skin Vegetations:A Case Report

Introduction:Primary systemic amyloidosis is characterized by clonal plasma cell disorder,and its signs and symptoms are various and complex,damage to the skin and mucous membrane is often more likely to attract attention.Here we reported a case of a 61-year-old male patient who presented with topical mucocutaneous lesion,as well unusual skin vegetations.Case presentation:A 61-year-old man was hospitalized due to repeated burning sensation on his back,multiple ecchymosis,and skin vegetations.Through a series of examinations(mainly including skin histopathology,bone marrow cytology,bone marrow flow cytometry,immunofixation electrophoresis),Primary systemic amyloidosis was diagnosed,but multiple myeloma could not be diagnosed.Subsequently,he received chemotherapy.In the half-year follow-up,there was no significant change in his symptoms and signs.Discussion:In this case,in addition to the typical skin damage of primary amyloidosis,the multiple skin vegetations in the buttocks,abdomen,and arms are particularly noteworthy.According to the histopathology and Immunohistochemistry of the skin vegetation,we infer that the formation mechanism of these skin vegetation is lymphatic obstruction caused by amyloid,which leads to lymphatic dilatation,lymph leakage,and dermal edema.Conclusion:Primary systemic amyloidosis is a rare disease,which is often difficult to diagnose.We should be alert to those atypical skin features so as not to delay diagnosis.

Immunophenotypic analysis of abnormal plasma cell clones in bone marrow of primary systemic light chain amyloidosis patients

Background Primary systemic light chain amyloidosis （AL） is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry （FCM） could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma （MM）,and 5 Waldenstr（o）m＇s macroglobulinemia （WM） patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases （60.9%）,in which the λ light chain restriction was found in 24 cases （77.4%）.In MM,κ light chain restriction was found in 13 cases （61.9%）,and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56＋,68.6% were CD117＋,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56＋,38.1% were CD117＋,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19＋ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.

Recent advances in transthyretin amyloidosis therapy

Mutant(MT)forms of transthyretin(TTR)cause the most common type of autosomal-dominant hereditary systemic amyloidosis—familial amyloidotic polyneuropathy(FAP).Until 20 years ago,FAP was thought to be an endemic disease,but FAP is known to occur worldwide.To date,more than 130 mutations in the TTR gene have been reported.Genotype-phenotype correlations are seen in FAP,and some variation in clinical presentation is often observed in individual kindreds with the same mutation and even among family members.Of the pathogenic TTR mutations,Val30Met was the first to be identified and is the most frequent known mutation found throughout the world.Studies of patients with FAP amyloidogenic TTR(ATTR)Val30Met documented sensorimotor polyneuropathy,autonomic dysfunction,heart and kidney failure,gastrointestinal tract(GI)disorders,and other symptoms leading to death,usually within 10 years of the onset of disease.Diagnosis is sometimes delayed,especially in patients without a clear family history and typical clinical manifestations,since diagnosis requires various studies and techniques such as histopathology,genetic testing,and mass spectrometry.For treatment of FAP,liver transplantation(LT)reportedly halts the progression of clinical manifestations.Exchange of an FAP patient’s diseased liver with a healthy liver causes MT TTR in the body to be replaced by wild-type(WT)TTR.Although clinical evaluations indicated that progression of other clinical symptoms such as peripheral neuropathy,GI symptoms,and renal involvement usually halted after LT in FAP ATTR Val30Met patients,recent studies suggested that LT failed to prevent progression of cardiac amyloidosis in FAP ATTR Val30Met patients after LT,with this failure reportedly being due to continued formation of amyloid that derived mainly from WT TTR secreted from the transplanted non-mutant liver graft.In recent years,many therapeutic strategies have been proposed,and several ongoing therapeutic trials involve,for example,stabilizers of TTR tetramers(tafamidis and diflunisal)and gene therapies to suppress TTR expression(antisense methods and use of small interfering RNAs).These novel therapies may prove to prevent progression of FAP.