scholarly journals Renal Involvement in Hereditary Transthyretin Amyloidosis: An Italian Single-Centre Experience

2021 ◽  
Vol 11 (8) ◽  
pp. 980
Author(s):  
Pietro Manuel Ferraro ◽  
Viola D’Ambrosio ◽  
Andrea Di Paolantonio ◽  
Valeria Guglielmino ◽  
Paolo Calabresi ◽  
...  
Keyword(s):  
Renal Involvement ◽  
Gene Mutations ◽  
Diagnostic Challenge ◽  
Transthyretin Amyloidosis ◽  
Protein Excretion ◽  
Single Centre Experience ◽  
Kidney Involvement ◽  
Single Predictor ◽  
Hereditary Transthyretin Amyloidosis ◽  
Over Time

Objective: Hereditary transthyretin amyloidosis (ATTRv) represents a diagnostic challenge considering the great variability of clinical presentation and multiorgan involvement. In the present study, we report the prevalence of kidney involvement and kidney function over time in a cohort of ATTRv patients with different transthyretin gene mutations. Patients and Methods: For this study, we systematically collected data from all patients with a diagnosis of ATTRv followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Kidney involvement was defined as presence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 obtained with CKD-EPI equation, abnormal urinary protein excretion (UPE) (>150 mg/24 h) and/or albuminuria >30 mg/24 h (or mg/g creatinine). The analysis included data from 46 patients with 122 measurements of serum creatinine. Results: Among the 46 patients included in the analysis, kidney involvement was present in 37%, with 15% showing reduced eGFR and 22% abnormal UPE (63% of patients with available UPE data). No single predictor was associated with either eGFR values or its slope over time. Conclusions: Kidney involvement is quite common in patients with ATTRv regardless of the underlying genetic variant. In particular, abnormal UPE appears to be a common feature of the disease.

scholarly journals Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

2020 ◽  
Vol 29 (3) ◽  
pp. 339-343
Author(s):  
Marco Luigetti ◽  
Annalisa Tortora ◽  
Angela Romano ◽  
Andrea Di Paolantonio ◽  
Valeria Guglielmino ◽  
...  
Keyword(s):  
Disease Onset ◽  
Gastrointestinal Symptoms ◽  
Diagnostic Challenge ◽  
Gene Encoding ◽  
Transthyretin Amyloidosis ◽  
Gastrointestinal Manifestations ◽  
Single Centre Experience ◽  
Gi Symptoms ◽  
Monitoring Visit ◽  
Almost All

Background and Aims: Hereditary transthyretin (ATTRv) amyloidosis represents a diagnostic challenge considering the great variability in clinical presentation and multiorgan involvement. In this study we report the prevalence of gastrointestinal (GI) involvement of patients with hereditary ATTRv amyloidosis from one single center of Italy, a non-endemic area. Methods: We retrospectively analyzed a cohort of 39 patients with hereditary ATTRv amyloidosis followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy. All patients had a documented mutation in the gene encoding the thansthyretin. Neurological, cardiological and gastrointestinal manifestations were systematically collected at every monitoring visit. Results: 82% reported at least one GI symptom. Unintentional weight loss was the most frequently reported. Lower GI symptoms were more frequent than upper GI symptoms (66.7% vs. 35.9%, p=0.0122). The first GI symptom was always reported within 5 years since disease onset. Gastrointestinal symptoms were almost always present in patients with Val30Met mutation (93.8%, 15/16), and in more than half of the cases with Phe64Leu mutation (66.7%, 8/12). All cases with a non-Val30Met mutation disclosed almost all GI symptoms within 5 years since disease onset; conversely, patients with Val30Met mutation continued to develop further GI manifestations during the disease course. Conclusions: Prevalence of GI symptoms in our cohort was 82%, resulting in a higher prevalence than reported in the THAOS registry. Gastroenterologists, therefore, play an important role for the management of the disease, and their expertise should be valued for an effective multidisciplinary approach to this condition.

A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Varvara Kanti ◽  
Lia Puder ◽  
Irina Jahnke ◽  
Philipp Maximilian Krabusch ◽  
Jan Kottner ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Skin Pigmentation ◽  
Gene Mutations ◽  
Continuous Treatment ◽  
Whole Body ◽  
Hair Color ◽  
Phase 2 ◽  
Loss Of Function ◽  
The Impact ◽  
Over Time

<b><i>Background and Objectives:</i></b> Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist <i>setmelanotide</i> in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with <i>setmelanotide,</i> changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. <b><i>Methods:</i></b> In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist <i>setmelanotide</i>. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. <b><i>Results:</i></b> We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of <i>setmelanotide</i> treatment. <b><i>Discussion:</i></b> <i>Setmelanotide</i> treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

Characterization of population genetic structure of hereditary transthyretin amyloidosis in Bulgaria

Amyloid ◽  
2021 ◽  
pp. 1-7
Author(s):  
Zornitsa Pavlova ◽  
Stayko Sarafov ◽  
Tihomir Todorov ◽  
Andrey Kirov ◽  
Teodora Chamova ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Population Genetic Structure ◽  
Population Genetic ◽  
Transthyretin Amyloidosis ◽  
Hereditary Transthyretin Amyloidosis

Genomic screening identifies individuals at high risk for hereditary transthyretin amyloidosis

2021 ◽  
Vol 132 ◽  
pp. S348-S349
Author(s):  
Emily Soper ◽  
Sabrina A. Suckiel ◽  
Giovanna Braganza ◽  
Amy Kontorovich ◽  
Eimear Kenny ◽  
...  
Keyword(s):  
High Risk ◽  
Transthyretin Amyloidosis ◽  
Genomic Screening ◽  
Hereditary Transthyretin Amyloidosis

Natural course of untreated cluster headache: A retrospective cohort study

Cephalalgia ◽  
2017 ◽  
Vol 38 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Mi Ji Lee ◽  
Hyun Ah Choi ◽  
Jong Hwa Shin ◽  
Hea Ree Park ◽  
Chin-Sang Chung
Keyword(s):  
Cluster Headache ◽  
Disease Duration ◽  
Medical Center ◽  
Natural Course ◽  
Duration Of Disease ◽  
Lost To Follow Up ◽  
Active Patients ◽  
Single Predictor ◽  
Over Time

Objective To determine the natural course of cluster headache. Methods We screened patients with cluster headache who were diagnosed at Samsung Medical Center and lost to follow-up for ≥5 years. Eligible patients were interviewed by phone about the longitudinal changes in headache characteristics and disease course. Remission was defined as symptom-free 1) for longer than twice the longest between-bout period and 2) for ≥5 years. Results Forty-two patients lost to follow-up for mean 7.5 (range, 5.0–15.7) years were included. The length of the last bout did not differ from the first one, while the last between-bout period was longer than the first one ( p = 0.012). Characteristics of cluster headache decreased over time: Side-locked unilaterality (from 92.9% to 78.9%), seasonal and circadian rhythmicity (from 63.9% to 60.9% and from 62.2 to 40.5%, respectively), and autonomic symptoms (from 95.2% to 75.0%). Remission occurred in 14 (33.3%) patients at a mean age of 42.3 (range, 27–65) years, which was not different from the age of last bouts in active patients ( p = 0.623). There was a trend for more seasonal and circadian predilection at baseline in the active group ( p = 0.056 and 0.063, respectively) and fewer lifetime bouts and shorter disease duration in patients in remission ( p = 0.063 and 0.090). Conclusions This study first shows the natural courses of cluster headache. Features of cluster headache become less prominent over time. Remission occurred regardless of age. Although no single predictor of remission was found, our data suggest that remission of cluster headache might not be a consequence of more advanced age, longer duration of disease, or accumulation of lifetime bouts.

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