Hospital Italiano de Montevideo

Las amiloidosis son enfermedades causadas por el depsito patolgico extracelular de un material proteico fibrilar e insoluble denominado amiloide, que puede estar vinculado a cadenas livianas (AL) o transtirretina (TTR). La amiloidosis cardaca provoca una cardiomiopata restrictiva de carcter progresivo caracterizada por falla cardaca con funcin sistlica relativamente preservada, que se asocia a elevada mortalidad. Aunque el diagnstico definitivo tradicionalmente se basa en la biopsia endomiocrdica, los avances en imagenologa han mejorado su abordaje y la reciente introduccin de terapias especificas permiten augurar cambios significativos en el pronstico. El tratamiento difiere segn el tipo de amiloide involucrado y su resultado depende de la instauracin precoz de este, por lo cual resulta esencial un diagnstico preciso y temprano. El centellograma cardaco con fosfatos marcados (99mTc-PYP u otros), ampliamente disponible y de relativo bajo costo, se considera en la actualidad como una "biopsia molecular no invasiva" para el diagnstico de la amiloidosis tipo ATTR, que debe ser usado en conjunto con la investigacin de protenas monoclonales en pacientes con sospecha clnica de la enfermedad.

La atrofia muscular espinal y bulbar es una enfermedad neurologica caracterizada por degeneracion gradual de la motoneurona inferior, que resulta en debilidad muscular, atrofia y fasciculaciones. Es una entidad de etiologia genetica con mecanismo de herencia ligado al cromosoma X recesivo, por lo que afecta a varones, en la que se produce una expansion del triplete CAGn en el gen del receptor de androgenos. Se manifiesta por signos de insensibilidad a los androgenos (ginecomastia e infertilidad). A partir de los 20-30 anos, aproximadamente, comienzan los signos de afectacion de la motoneurona inferior a nivel espinal con calambres y temblor de accion y posteriormente debilidad muscular. En la evolucion se evidencia compromiso bulbar. Se presenta el caso clinico-genealogico de un varon de 32 anos con temblores en quien se confirma molecularmente la enfermedad de Kennedy. Este es el primer caso, hasta nuestro conocimiento, reportado en Uruguay. Se destaca la importancia de plantear dicha afeccion en un paciente joven con “temblores” cuando aun no es ostensible la debilidad muscular. La historia familiar es de capital importancia. La presencia de fasciculaciones en el estudio electrico a nivel perioral es muy sugestiva de esta patologia. La confirmacion molecular es importante para el asesoramiento genetico.

Mucopolysaccharidosis type I is a rare autosomal recessive disorder caused by deficiency of α-l-iduronidase (IDUA) which leads to a wide spectrum of clinical severity. Here, we describe the case of four male patients who present the previously undescribed p.L18P mutation. Patient 1 (p.L18P/p.L18P) presents, despite multiple joint contractures, an attenuated phenotype. Patient 2 (p.L18P/p.W402X) was diagnosed at 4 years of age with bone dysplasia, coarse facies, limited mobility, claw hands and underwent bilateral carpal tunnel surgery at 6 years of age. Patients 3 and 4 (both p.L18P/p.L18P) are brothers. Patient 3 was diagnosed at 4 years of age, when presented claw hands, lower limb and shoulder pain, restricted articular movement and bilateral carpal tunnel syndrome. Patient 4 was diagnosed at 17 months of age when presented lower limb pain at night, respiratory allergy and repeated upper airways infections. Bioinformatics analysis indicates that p.L18P mutation reduces the signal peptide to 25 amino acids and alters its secondary structure. In conclusion, we report a new IDUA variant that alters the structure of the signal peptide, which likely impairs transport to lysosomes. Moreover, it leads to a distinct attenuated phenotype with mainly bone and cartilage symptoms, without visceromegalies, heart disease, or cognitive impairment.

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase(®), Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.

A balanced complex chromosome rearrangement (CCR) involving three chromosomes is rare and may lead to different types of aneuploid germ cells. We report here a 14-year follow-up of a boy with a karyotype defined as 46,XY,der(18)t(6;13;18)(q21;q21.32;q22.3).ish der(18)(13qter+,18qter-) characterized by multiple congenital abnormalities, including distinctive minor facial anomalies, short neck, abnormalities of the extremities, anogenital abnormalities, flexion contractures, especially at extremities, and severe mental and growth retardation. Chromosome analysis in the mother showed a CCR involving chromosomes 6, 13, and 18. This CCR was the result of a three-break rearrangement, and the derivative chromosome 13 consisted of parts of chromosomes 18 and 13. The karyotype of the child was not balanced, and resulted in partial trisomy for 13q and partial monosomy for 18q detected prenatally by conventional and molecular cytogenetics. Although such a karyotype and its phenotype have not previously been reported, we have compared the clinical and cytogenetic data from our patient with previously described cases of partial trisomy 13q and monosomy 18q despite different break points. We are presenting a new CCR in a woman with normal phenotype with a history of four early abortions and a long follow-up of her malformed newborn with partial 13q trisomy and 18q monosomy.