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SINDROME DI ALSTROM
Codice esenzione : RN1370


La sindrome di Alstrom e un raro disordine autosomico recessivo caratterizzato da degenerazione retinica, obesita progressiva perdita dell'udito, dibete mellito non-insulino dipendente, insufficienza renale ed epatica (Maffei P, Munno V, Marshall JD, Scandellari C, Sicolo N. The Alstrom syndrome: is it a rare or unknown disease? Ann Ital Med Int. 2002;17(4):221-228).

Tutti gli individui affetti manifestano retinopatia pigmentaria progressiva, obesita infantile, e ipoacusia sensoriale da lieve a moderata. Nei giovani adulti insorge il diabete mellito non-insulino dipendente.
Tutti gli individui affetti manifestano retinopatia pigmentaria progressiva, obesita infantile, e ipoacusia sensoriale da lieve a moderata. Nei giovani adulti insorge il diabete mellito non-insulino dipendente. Negli stadi finali della malattia i pazienti presentano una nefropatia cronica progressiva con eventuale evoluzione verso l'insufficienza renale, che e la piu frequente causa di morte. Vi possono essere anche insufficienza epatica, malattia arteriosclerotica e scompenso cardiaco congestizio secondario a cardiomiopatia dilatativa (Marshall JD, Ludman MD, Shea SE, Salisbury SR, Willi SM, LaRoche RG, Nishina PM. Genealogy, natural history, and phenotype features of Alstrom syndrome in a large Acadian Kindred and three additional families. Am J Med Genet. 1997;73(2):150-161).

Data la natura progressiva della malattia sono state stilate dell linee guida per il monitoraggio dei pazienti affetti da Sindrome di Alstrom.
Le seguenti valutazioni clinico-strumentali sono importanti per il monitoraggio dei pazienti affetti da Sindrome di Alstrom:
1. controllo della visione, ERG nella fanciullezza;
2. valutazione audiometria annuale;
3. valutazione del BMI;
4. test di funzionalita cardiaca, ECG e ecocardiografia annuali o semestrali se necessario;
5. glicemia, test da carico e insulinemia;
6. misurazione della pressione arteriosa;
7. ecografia epatica;
8. controllo ematico della funzionalita renale (crestinina, acido urico, clearance della creatinina, BUN), della funzionalita epatica (ALT, AST, GGT), pannello lipidico (colesterolo e trigliceridi);
9. funzione tiroidea (TSH, T4), con particolare attenzione all'eventuale ipotiroidismo subclinico;
10. valutazione del tratto gastrointestinale, e del reflusso gastroesofageo;
11. funzione gonadica (LH, FSH, testosterone);
12. test di funzionalita polmonare;
13. osservazione dell'eventuale presenza di disfunzioni urinarie;
14. presenza di alterazioni scheletriche, scoliosi, cifosi;
15. valutazione neurologica (atassia, epilessia)
(www.jax.org/alstrom).

Il gene responsabile della sindrome, ALMS1, localizzato sul braccio corto del cromosoma 2 (2p13), e stato clonato, ma il meccanismo patogenetico che sottende l'involuzione multiorgano della sindrome e ancora sconosciuto (Maffei P, Munno V, Marshall JD, Scandellari C, Sicolo N. The Alstrom syndrome: is it a rare or unknown disease? Ann Ital Med Int. 2002;17(4):221-228).
La funzione di ALMS1 non e chiara. Il gene presenta delle somiglianze nell'organizzazione strutturale con i geni per le mucine, ma ALMS1 non e una mucina. ALMS1 e una nuova proteine coinvolta in una sindrome di insulino-resistenza e questo rappresenta una possibile nuova via patogenetica (Hearn T, Renforth GL, Spalluto C, Hanley NA, Piper K, Brickwood S, White C, Connolly V, Taylor JF, Russell-Eggitt I, Bonneau D, Walker M, Wilson DI. Mutations of ALMS1, a large gene with tandem repeat encoding 47 amino acids, causes Alstrom syndrome. Nature Genetics 2002; 31(1):79-83).

La sindrome di Alstrom e un complesso di malattie multiorganosistemiche. La diagnosi e difficile perche i vari fenotipi si presentano consecutivamente e assomiglia ad altre sindromi. Ci sono molti diversi modi di coinvolgimento dei vari organi e inoltre si manifesta con alcuni aspetti non generalmente conosciuti della sindrome. In molti pazienti si manifestano patologie a carico si polmoni, apparato gastrointestinale e urologico. Tuttavia la presenza di anormalita digitali e alterazioni neurologiche rende confusa la diagnosi differenziale con la sindrome di Bardet-Biedl.
I pazienti con Sindrome di Alstrom hanno una fibrosi multiorgano. Non e noto se tale fibrosi sia determinata direttamente dall'alterazione genetica o se sia invece il risultato di un'infiammazione cronica.
Non sono state trovati aspetti clinici che distinguano i pazienti nei quali e stata riconosciuta la mutazione genetica, da quelli in cui non e stata identificata (Marshall JD, Bronson RT, Collin GB, Nordstrom AD, Maffei P, Paisey RB, Carey C, Macdermott S, Russell-Eggitt I, Shea SE, Davis J, Beck S, Shatirishvili G, Mihai CM, Hoeltzenbein M, Pozzan GB, Hopkinson I, Sicolo N, Naggert JK, Nishina PM. New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med. 2005;165(6):675-83).

E necessario un approccio multidisciplinare per trattare la sindrome di Alstrom, caratterizzato da un team di specialisti. La sindrome di Alstrom coinvolge pesantemente non solo il paziente, ma anche la sua famiglia, per cui il team che segue il paziente deve essere pronto a risolvere i problemi di tutti i giorni. Considerando la complessita della sindrome sarebbe bene che coordinatori del team fossero un pediatra nell'infanzia-adolescenza e poi un'internista nell'eta adulta. Sarebbe bene che facessero parte del team anche esperti non medici, quali psicologi, insegnati per disabili, dietisti, per aiutare meglio il paziente nella vita di tutti i giorni (Marshall JD, Bronson RT, Collin GB, Nordstrom AD, Maffei P, Paisey RB, Carey C, Macdermott S, Russell-Eggitt I, Shea SE, Davis J, Beck S, Shatirishvili G, Mihai CM, Hoeltzenbein M, Pozzan GB, Hopkinson I, Sicolo N, Naggert JK, Nishina PM. New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med. 2005;165(6):675-83).

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