ABSTRACT
HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.
Subject(s)
Claudins , Humans , Male , Claudins/genetics , Adult , Ichthyosis/genetics , Ichthyosis/pathology , Hypohidrosis/genetics , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/pathology , Pedigree , PhenotypeABSTRACT
Background: Acute hepatic porphyria (AHP) comprises a group of rare genetic diseases characterized by neurovisceral crises that are manifested by abdominal pain and neurological and/or psychological symptoms that interfere with the ability to lead a normal life. Our objective was to determine the burden of the disease in one year and the health-related quality of life (HRQoL) in patients with AHP. Results: 28 patients were analyzed. The mean age was 36.6±10.2 years, 89.3% were women, and the average number of crises was 1.9±1.5. The average annual cost per patient was 38,255.40. 80.2% of the costs was direct medical costs, 17.5% was associated with loss of productivity and 2.3% was direct non-medical costs. 85.9% of the total cost corresponded to the crises. The intercrisis period accounted for the remaining 14.1%. The global index of the EQ-5D-5L (HRQoL) was 0.75±0.24. The dimensions of pain/discomfort, anxiety/depression and daily activities were the most affected. Leisure, travel/vacations and household activities were the most affected daily activities. 53.6% of patients required a caregiver due to AHP. 92.9% did not present overload and 7.1% presented extreme overload. Conclusions: Patients with AHP are associated with a high economic impact and an affected HRQoL in the pain/discomfort dimension, with a negative impact on the performance of daily activities and a risk of psychiatric diseases.(AU)
Antecedentes: La porfiria hepática aguda (PHA) comprende un grupo de enfermedades genéticas raras caracterizadas por crisis neuroviscerales que se manifiestan por dolor abdominal y síntomas neurológicos y/o psicológicos que interfieren en la capacidad de llevar una vida normal. Nuestro objetivo fue determinar la carga de la enfermedad en un año y la calidad de vida relacionada con la salud (CVRS) en pacientes con PHA. Resultados: Se analizaron 28 pacientes. La edad media fue de 36,6±10,2 años, el 89,3% eran mujeres y la media de crisis fue de 1,9±1,5. El coste medio anual por paciente fue de 38.255,40. El 80,2% de los costes fueron costes médicos directos, el 17,5% estuvieron asociados a pérdida de productividad y el 2,3% fueron costes directos no médicos. El 85,9% del coste total correspondió a las crisis. El período entre crisis representó el 14,1% restante. El índice global del EQ-5D-5L (HRQoL) fue de 0,751±0,24. Las dimensiones de dolor/malestar, ansiedad/depresión y actividades cotidianas fueron las más afectadas. Ocio, viajes/vacaciones y actividades del hogar fueron las actividades diarias más afectadas. El 53,6% de los pacientes requirieron un cuidador debido a la PHA. El 92,9% no presentaron sobrecarga y el 7,1% presentaron sobrecarga extrema. Conclusiones: Los pacientes con PHA se asocian con un alto impacto económico y una CVRS afectada en la dimensión dolor/malestar, con impacto negativo en el desempeño de las actividades diarias y riesgo de enfermedades psiquiátricas.(AU)
Subject(s)
Humans , Male , Female , Adult , Porphyrias, Hepatic/diagnosis , Quality of Life , Cost of Illness , Rare Diseases/economics , Genetic Diseases, Inborn/economics , Clinical MedicineABSTRACT
BACKGROUND: Acute hepatic porphyria (AHP) comprises a group of rare genetic diseases characterized by neurovisceral crises that are manifested by abdominal pain and neurological and/or psychological symptoms that interfere with the ability to lead a normal life. Our objective was to determine the burden of the disease in one year and the health-related quality of life (HRQoL) in patients with AHP. RESULTS: 28 patients were analyzed. The mean age was 36.6±10.2 years, 89.3% were women, and the average number of crises was 1.9±1.5. The average annual cost per patient was 38,255.40. 80.2% of the costs was direct medical costs, 17.5% was associated with loss of productivity and 2.3% was direct non-medical costs. 85.9% of the total cost corresponded to the crises. The intercrisis period accounted for the remaining 14.1%. The global index of the EQ-5D-5L (HRQoL) was 0.75±0.24. The dimensions of pain/discomfort, anxiety/depression and daily activities were the most affected. Leisure, travel/vacations and household activities were the most affected daily activities. 53.6% of patients required a caregiver due to AHP. 92.9% did not present overload and 7.1% presented extreme overload. CONCLUSIONS: Patients with AHP are associated with a high economic impact and an affected HRQoL in the pain/discomfort dimension, with a negative impact on the performance of daily activities and a risk of psychiatric diseases.
Subject(s)
Porphyrias, Hepatic , Quality of Life , Humans , Female , Adult , Middle Aged , Male , Depression/etiology , Cost of Illness , Pain/etiologyABSTRACT
El síndrome de Paget-Schroetter (SPS) en el contexto de trombosis venosa profunda (TVP) de miembro superior es una patología poco frecuente pero de gran importancia por afectar personas sanas y jóvenes, donde el síndrome postrombótico (SPT) secundario puede ser una complicación con importantes implicaciones. La mejor opción de tratamiento es controvertida. Las guías actuales recomiendan anticoagulación durante un mínimo de 3 meses, aunque se han visto con este manejo incidencias de SPT cercanas al 50% a los 6 meses, al 30% al año y al 25% a los 2 años, por lo que unidades especializadas abogan por la realización de trombólisis local y cirugía descompresiva precoz, con el propósito de disminuir estas cifras. Describimos una serie de 8 casos, a los que tratamos de esta última manera. Ningún paciente presentó complicaciones, y en todos se observó reintegro precoz a la actividad diaria, con ausencia de SPT en el 90% de ellos
Paget-Schroetter syndrome (PSS) in the context of upper extremity deep venous thrombosis (DVT) is an uncommon but potentially very serious condition affecting young, healthy adults, in which secondary post-thrombotic syndrome (PTS) can be a complication with major implications. The best treatment option remains controversial, with current guidelines recommending anticoagulation for at least 3 months. However, an incidence of PTS of approximately 50% after 6 months, 30% after 1 year and 25% after 2 years has been found using this therapeutic approach. Consequently, specialized units recommend local thrombolysis and early decompressive surgery. We describe a series of eight cases treated in this way. None of the patients showed signs of complications, and an early return to regular activities with no PTS was observed in 90% of cases
Subject(s)
Adult , Female , Humans , Male , Young Adult , Upper Extremity Deep Vein Thrombosis/therapy , Thoracic Outlet Syndrome/therapy , Patient Care Team/organization & administration , Early Diagnosis , Prospective Studies , Thrombolytic TherapyABSTRACT
Paget-Schroetter syndrome (PSS) in the context of upper extremity deep venous thrombosis (DVT) is an uncommon but potentially very serious condition affecting young, healthy adults, in which secondary post-thrombotic syndrome (PTS) can be a complication with major implications. The best treatment option remains controversial, with current guidelines recommending anticoagulation for at least 3 months. However, an incidence of PTS of approximately 50% after 6 months, 30% after 1 year and 25% after 2 years has been found using this therapeutic approach. Consequently, specialized units recommend local thrombolysis and early decompressive surgery. We describe a series of eight cases treated in this way. None of the patients showed signs of complications, and an early return to regular activities with no PTS was observed in 90% of cases.
Subject(s)
Anticoagulants/therapeutic use , Decompression, Surgical , Disease Management , Heparin, Low-Molecular-Weight/therapeutic use , Postthrombotic Syndrome/prevention & control , Thrombolytic Therapy , Upper Extremity Deep Vein Thrombosis/therapy , Adolescent , Adult , Anticoagulants/administration & dosage , Combined Modality Therapy , Cumulative Trauma Disorders/drug therapy , Cumulative Trauma Disorders/etiology , Cumulative Trauma Disorders/surgery , Disease-Free Survival , Endovascular Procedures , Female , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Interdisciplinary Communication , Male , Neck Muscles/surgery , Occupational Diseases/drug therapy , Occupational Diseases/etiology , Occupational Diseases/surgery , Patient Care Team , Prospective Studies , Recurrence , Ribs/surgery , Upper Extremity Deep Vein Thrombosis/drug therapy , Upper Extremity Deep Vein Thrombosis/etiology , Upper Extremity Deep Vein Thrombosis/surgery , Weight Lifting , Young AdultSubject(s)
Calcinosis/etiology , Femoral Artery/injuries , Magnetic Resonance Imaging , Muscle, Skeletal/injuries , Muscular Diseases/etiology , Wounds, Gunshot/complications , Calcinosis/pathology , Collateral Circulation , Embolization, Therapeutic , Female , Femoral Artery/pathology , Humans , Middle Aged , Muscle, Skeletal/blood supply , Muscle, Skeletal/pathology , Muscular Diseases/pathology , Muscular Diseases/therapy , Necrosis , Thigh/injuries , Time FactorsABSTRACT
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