Biochemical and clinical permanent remission in argentinian population. An overview of the last 36 years.

MELITO, V; ROSSETTI, M.V; BATLLE, A; PARERA, V

Lucerna

Congreso; International Congress of Porphyrins and Porphyrias; 2013

Acute intermittent porphyria (AIP), inherited as an autosomal dominant trait, is caused by a defect in the gene codifying for porphobilinogen deaminase (PBG-D). Clinical expression occurs after puberty; environmental and other factors such as fasting, drugs, alcohol, steroid hormones, stress, may precipitate acute attacks, begining with abdominal pain followed by the development of peripheral neuropathy and central nervous system manifestations. Heme precursors ä - aminolevulinic acid (ALA) and porphobilinogen (PBG) are significantly increased, often, values can also be higher than normals when patients are in remission after having had a first crisis. Complete clinical recovery of peripheral neuropathy might require several months. AIP is inherited as an autosomal dominant trait with a prevalence of 1:125000 in Argentina. In women about 40 % are symptomatic patients, while in men only 4 % of the latent AIP develop the clinical signs. Since 1976, we have diagnosed 168 AIP families, with more than one affected member in each family. Treatment during acute attacks consists in administration of glucose, folic acid, and a complex of B vitamins or hematin if available. Administration of relatively high amounts of carbohydrates, is the fundamental base of the nutritional treatment, during both the attack and the asymptomatic periods, given as a personalized diet by one specialized nutritionist. Carbohydrates appear to act through the mechanism known as ? glucose effect ? , inhibiting the induction of the regulatory enzyme ALA-synthetase. For this study, we have selected 24 patients, belonging to 22 unrelated families, 23 women and 1 man who were diagnosed when they were 19-48 years old. The values of precursors at diagnosis were ranging between 4.9 to 47.7 mg/24h for ALA and 12.6 to 185.0-mg/24h. After treatment ALA (4 mg/24h) and PBG (2 mg/24h) finally diminished to normal values. Once reaching remission, these patients have continued with the folic acid, glucose and Vitamines B complex maintenance treatment, without developing another crisis ever. This recovery is not related to the mutation detected in the PBG-D gene, we have described 16 different genetic variants in these 22 families. In conclusion, the correct clinical management of the porphyric patients lead to a more rapid recovery from the crisis and, as already stated, a much longer and permanent remission, interestingly, they did not suffer another attack for the rest of their lives, up today.