Hemocromatosis herediataria Tipo I. Presentación de un caso / Type I hereditary hemocrhomatosis. Case presentation

La hemocromatosis hereditaria es una enfermedad genética de difícil diagnóstico, en estadios iniciales, ocasionada por alteraciones en el metabolismo del hierro; que conllevan a su depósito en diversos tejidos y como resultado una gran morbilidad en los pacientes afectados. A través de este trabajo se realizó la presentación del primer caso diagnosticado por gastroenterólogos, en el Hospital Faustino Pérez de Matanzas. El paciente debutó con síntomas relacionados con la esfera endocrina como: impotencia, pérdida de la líbido y de la eyaculación. Después de efectuar los estudios correspondientes se concluyó como un hipogonadismo hipogonadotrópico post puberal, por presentar elevación de las enzimas hepáticas. Fue remitido a consulta de Hepatología donde se completó su estudio, confirmándose el diagnóstico de hemocromatosis hereditaria tipo I, a través de biopsia hepática y estudios genéticos (AU).

Hereditary hemocrhomatosis is a genetic disease of difficult diagnosis in its early stages, caused by alterations in the iron metabolism; it leads to iron storage in several tissues and consequently to a great morbidity in affected patients. In this work, we presented the first case diagnosed by gastroenterologists in the Hospital Faustino Pérez, of Matanzas. The patient began with symptoms related with the endocrine sphere like impotence, and lost of libido and ejaculation. After finishing the correspondent studies, we arrived to the conclusion of post-pubertal hypogonadotropic hypogonadism: the patient presented hepatic enzymes elevation. He was referred to Hepatology consultation where the study was finished, confirming the diagnosis of Type I hereditary hemocrhomatosis through biopsy and genetic studies (AU).

Regulación de la hepcidina y homeostasis del hierro: avances y perspectivas / Regulation of hepcidin and iron homeostasis: progress and prospects

El estudio de los desórdenes genéticos del metabolismo del hierro, la identificación de sus transportadores y el descubrimiento de la hepcidina, hormona reguladora de la homeostasia del hierro, han contribuido grandemente a aumentar los conocimientos sobre este metabolismo y han cambiado sustancialmente la visión sobre las enfermedades relacionadas con alteraciones del metabolismo férrico. En la última década, no solo se han esclarecido elementos de la patogénesis de estas enfermedades, sino que ya se vislumbran aplicaciones terapéuticas de estos avances. Así, ya se habla de una nueva era basada en el tratamiento de los desórdenes de la homeostasia del hierro a través de la modulación de la hepcidina

The study of genetic disorders of iron metabolism, identification of transporters and the discovery of hepcidin- a hormone regulating iron homeostasis- have contributed greatly to increase awareness of this metabolism. Substantially, the vision on diseases related to disorders of iron metabolism has been changed. In the last decade, elements of the pathogenesis of these diseases have not only been clarified, but therapeutic applications of these advances are looming. Thus, there are expectations of a new era based on the treatment of iron homeostasis disorders through hepcidin modulation

Molecular and pathological basis of aceruloplasminemia

Aceruloplasminemia is an autosomal recessive neurodegenerative disease characterized by iron accumulation in the brain as well as visceral organs. It is a loss-of-function disorder caused by mutations in the ceruloplasmin gene. Clinically, this disease consists of the triad of adult-onset neurological disease, retinal degeneration and diabetes mellitus. Massive iron accumulation and extensive loss of neurons are observed in the basal ganglia. The elevated iron concentration is associated with increased lipid peroxidation in the brains of aceruloplasminemia patients. Enlarged or deformed astrocytes and spheroid-like globular structures are characteristic neuropathological findings in aceruloplasminemia. Moreover, deformed astrocytes and globular structures react positively to anti-4-hydroxynonenal antibody, suggesting that increased oxidative stress is involved in neuronal cell death in aceruloplasminemia brain. More than 30 aceruloplasminemia-causing mutations in the ceruloplasmin gene have been identified. We examined the biosynthesis of two missense ceruloplasmin proteins that result from a Japanese P177R mutation and a Dutch G631R mutation, using Chinese hamster ovary cell expression system. The P177R mutant protein is retained in the endoplasmic reticulum. The G631R mutant protein, predicted to alter the interactions at a single type I copper-binding site, prevented incorporation of copper into apoceruloplasmin and resulted in the synthesis and secretion only of apoceruloplasmin. Molecular analysis of missense mutations showed different structure-function relationships in ceruloplasmin protein. The investigation of mutant ceruloplasmin reveals new insights into molecular pathogenesis of aceruloplasminemia as well as biosynthesis, trafficking, and function of ceruloplasmin.