Clinically Meaningful Outcomes after 1 Year of Treatment with Setmelanotide in an Adult Patient with a Variant in SH2B1.

INTRODUCTION: Monogenic obesity is caused by a unique genetic dysfunction, often appears in childhood, and can be accompanied by neuroendocrine, skeletal, developmental, and behavioral disorders, among other manifestations. Some variants in the SH2B1 gene have been suggested as strong candidates for the development of autosomal dominant obesity. CASE PRESENTATION: We describe here the clinical response after 1 year of setmelanotide treatment in a 22-year-old patient with an SH2B1 variant. After 3 months of treatment, our patient lost 5.4% of body weight. This period was followed by a 3-month period of noncompliance, in which the patient gained 4% body weight. After reinstating daily drug administration, the patient showed a 19.5% reduction in body weight and a clear improvement in all hunger scales after 1 year of treatment. CONCLUSION: These results indicate that the changes seen are drug dependent and provide positive evidence for the administration of setmelanotide in adult patients with heterozygous variants in the SH2B1 gene.

Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment.

AIMS: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. METHODS: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. RESULTS: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. CONCLUSION: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Abstract Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of glycolipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at a young age. Neuropathic pain and pain attacks are often the presenting symptoms of the disease and start at an average age of 9 years in male patients and 16 years in female patients, but currently a systematic literature review in early childhood showed the presence of these symptoms before the age of 5 years. Clinical studies have shown that enzyme replacement therapy may improve the overall pain scores and pain intensity in patients; improvements in pain outcomes have been sustained during the long-term follow-up, allowing many patients to reduce their use of pain medication. Some indirect evidence from dose-switching studies suggests that enzyme replacement therapy dose may be of relevance to pain outcomes. Considering that damage to small nerve fibers occurs early, prompt treatment is important in order to limit damage to the peripheral nervous system. In this article a comprehensive overview of the existing literature on small nerve fiber pathophysiology and the relationship with neuropathic pain and treatment response in children and adults with Fabry disease is presented.

Treatment with agalsidase beta during pregnancy in Fabry disease.

Fabry disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase A, which leads to excessive accumulation of glycosphingolipids in most tissues in the body, with life-threatening clinical consequences in the kidney, heart, and cerebrovascular system. Enzyme replacement therapy using exogenously produced alpha-galactosidase has been available for treatment of this multisystem progressive disease since 2001. Two different preparations of enzyme replacement therapy for Fabry disease are available outside of the USA: agalsidase alfa and agalsidase beta. Despite being X-linked, Fabry disease affects many female patients, and this report presents a successful pregnancy of a female patient receiving agalsidase beta.

Ecografía renal en 25 pacientes con enfermedad de Fabry: incidencia de patología quística renal / Renal echography in 25 Fabry disease patients: cystic renal pathology incidence

La enfermedad de Fabry (EF) es una enfermedad por depósito lisosomal, con herencia ligada al X, causada por ladeficiencia de la enzima α-galactosidasa A, lo que lleva al acúmulo de glicoesfingolípidos en diferentes célulasdel organismo. La muerte de estos pacientes se da en el contexto de insuficiencia renal, cardiaca y cerebrovascular. Otros reportes demuestran que los pacientes con EFtienen una incidencia mayor de quistes renales que la población normal.Objetivo: evaluar en un grupo de 25 pacientes con EF los hallazgos ecográficos renales. Materiales y métodos: se evaluaron 25 pacientes (16 hemicigotas), 16-50 años, con diagnóstico confirmado por test bioquímicos y genéticos, sin insuficiencia renal. Resultados: los diámetros renales fueron normales, el24% del total de los evaluados presentaron quistes renales, con un total del grupo de los hemicigotas del 24% ydel total de las heterocigotas el 22,2% afectados. Conclusión: si bien el grupo de pacientes evaluados fue pequeño, hemos encontrado una incidencia mayor a la población normal, pero menor a los valores reportados por otros autores. (AU)

glycosphingolipid catabolism caused by the deficient activity of α-galactosidase A, that results in the progressiveaccumulation of globotriaosylceramide in different cells of organism. Patiens frequently die for renal or cardiacinsufficiency. Aim: to assess 25 patients (16 hemicygotes) with confirmdiagnosis of Fabry disease without renal insufficiency. Results: renal diameter were normal, 24% ot total patientsshowed cystic abnormalities.Conclusion: although our group was small, but we found a high incidence of cystic abnormalities compared withnormal population and smaller than other reports. (AU)

Ecografía renal en 25 pacientes con enfermedad de Fabry: incidencia de patología quística renal / Renal echography in 25 Fabry disease patients: cystic renal pathology incidence

La enfermedad de Fabry (EF) es una enfermedad por depósito lisosomal, con herencia ligada al X, causada por ladeficiencia de la enzima α-galactosidasa A, lo que lleva al acúmulo de glicoesfingolípidos en diferentes célulasdel organismo. La muerte de estos pacientes se da en el contexto de insuficiencia renal, cardiaca y cerebrovascular. Otros reportes demuestran que los pacientes con EFtienen una incidencia mayor de quistes renales que la población normal.Objetivo: evaluar en un grupo de 25 pacientes con EF los hallazgos ecográficos renales. Materiales y métodos: se evaluaron 25 pacientes (16 hemicigotas), 16-50 años, con diagnóstico confirmado por test bioquímicos y genéticos, sin insuficiencia renal. Resultados: los diámetros renales fueron normales, el24% del total de los evaluados presentaron quistes renales, con un total del grupo de los hemicigotas del 24% ydel total de las heterocigotas el 22,2% afectados. Conclusión: si bien el grupo de pacientes evaluados fue pequeño, hemos encontrado una incidencia mayor a la población normal, pero menor a los valores reportados por otros autores.

glycosphingolipid catabolism caused by the deficient activity of α-galactosidase A, that results in the progressiveaccumulation of globotriaosylceramide in different cells of organism. Patiens frequently die for renal or cardiacinsufficiency. Aim: to assess 25 patients (16 hemicygotes) with confirmdiagnosis of Fabry disease without renal insufficiency. Results: renal diameter were normal, 24% ot total patientsshowed cystic abnormalities.Conclusion: although our group was small, but we found a high incidence of cystic abnormalities compared withnormal population and smaller than other reports.

Magnetic resonance image findings in 5 young patients with Fabry disease.

INTRODUCTION: Fabry disease is an X-linked recessive lysosomal storage disease; it is due to alpha-galactosidase A deficiency, and its clinical course shows repeated small artery strokes. METHODS: Five patients diagnosed with Fabry disease (mean age +/- SD = 28.2 +/- 11.1 years) and 5 age-matched controls were evaluated with the following magnetic resonance image (MRI) sequences: T1, T2, FLAIR, diffusion, and single voxel spectroscopy at the parietal lobe. RESULTS: Conventional images did not reveal alterations. Mean apparent diffusion coefficient (ADC) +/- SD in the corona radiata of patients was 7.8 +/- 0.2 x 10 mm/s, which was significantly higher than for controls: 6.93 +/- 0.49 x 10 mm/s (P < 0.05). At the lenticular nucleus there were no differences in ADC values between patients (7.32 +/- 0.2 x 10 mm/s) and controls (7.2 +/- 0.2 x 10 mm/s). The mean ratio NAA/Cr +/- SD at the parietal lobes was 1.94 +/- 0.2 for patients and 2.1 +/- 0.13 for controls (P = n.s.). DISCUSSION: : In a group of young Fabry disease patients with normal MRIs, a significant increment of over 12% in ADC values in the corona radiata was found compared with age-matched controls. The change could reflect increased interstitial water content after the Starling equilibrium under raised cerebral blood flow, which is a known feature of Fabry disease. CONCLUSION: Raised ADC values could predate conventional MRI changes in Fabry disease and therefore be a more sensitive marker of disease progression and response to enzymatic replacement therapy.