Diagnostics of mucopolysaccharidoses presented through the case of sanfilippo syndrome

Abstract

Mucopolysaccharidoses (MPS) are recessive inheritable, progressive diseases of disordered degradation and storage of acid glucos-aminoglycans. A five-year old child with psychomotor development retardation, which started at his age of two, was presented in our study. Clinical examination showed big head with rough facial features, skeleton deformities and hepatosplenomegaly. The diagnosis Dysostosis epifisealis multiplex was also confirmed by the X-ray examination of skeleton. Karyotype: 46, XY. Mental retardation: IQ-48. Clinically suspected mucopolysaccharidosis called for metabolic screening of first morning urine and the positive toluidine blue test result indicated the increased excretion of mucopolysaccharides. Further enzyme analyses of peripheral blood leucocytes confirmed the heparin sulphate sulphatase deficiency on the basis of which A (MPS III) Sanfilippo syndrome was defined. Our patient was born as a twin sibling. The other sibling is clinically healthy and of normal metabolic screening. It was not possible to define precisely the healthy heterozygote by testing the enzyme activities. A large number of mutations at various loci and big genetic heterogeneity of mucopolysaccharidoses made molecular diagnostics difficult. In the subsequent pregnancy, the mother was recommended prenatal diagnostics by enzyme analysis from the cultured chorionic villus. The prognosis of the presented patient is bad, the course of the disease is progressive and the patient can be expected to die in spastic tetraplegia in the second decade of life. The treatment is symptomatic for the time being.Mukopolisaharidoze {MPS) su recesivno nasledne, progresivne bolesti poremecaja razgradnje i deponovanja kiselih glukozaminoglikana u lizozomima.U nasem radu je prikazano dete uzrasta od pet godina koje od druge godine zaostaje u psihomotornom razvoju. Klinickim pregledom ce uocavaju: velika glava sa grubim crtama lica, deformacije skeleta i hepatosplenomegalija. Na rendgenskom snimku skeleta potvrdjena je dijagnoza - Dysostosis epifisealis multiplex. Kariotip: 46, XY. Mentalna retardacija: IQ-48. Klinicka sumnja na mukopolisaharidozu indikovala je metabolicki skrining iz jutarnje mokrace, a pozitivan test Toluidin plavo ukazao je na povecanu ekskreciju mukopolisaharida. Dalju laboratorijsku dijagnostiku cine analize urinarnih glukozaminoglikana (kvantitativnim ili elektroforetskim frakcijama) i potvrda specificnog enzimskog deficita u leukocitima periferne krvi. Deficit heparan sulfamidaze definitivno postavlja dijagnozu Sanfilipovog (Sanfilippo) sindroma tip A (MPSIII). Nas bolesnik je rodjen iz blizanacke trudnoce, u kojoj je drugo dete klinicki zdravo i urednog metabolickog skrininga. Ispitivanjem enzimske aktivnosti ne moze ce precizno definisati zdrav heterozigot. Veliki broj mutacija na razlicitim lokusima i velika genska heterogenost mukopolisaharidoza otezava molekularnu dijagnostiku. U sledecoj trudnoci majci je preporucena prenatalna dijagnostika enzimskom analizom iz kultivisanih horionskih resica. Prognoza za bolesnika kojeg smo prikazali je losa, tok je progresivan, smrt nastaje u spastickoj kvadriplegiji u drugoj deceniji. Lecenjeje za sada simptomatsko.