Sfingolipidoz Tanısı ile İzlediğimiz Olguların Değerlendirilmesi: Tek Merkez Deneyimi

Bu çalışmada sfingolipidoz tanısı ile izlediğimiz hastaların klinik, demografik ve laboratuvar verilerinin değerlendirilmesi amaçlanmıştır. Bursa Uludağ Üniversitesi Tıp Fakültesi Çocuk Metabolizma Hastalıkları Bilim Dalında sfingolipidoz tanısı ile izlediğimiz 34 hasta geriye yönelik olarak değerlendirilmiştir. Hastaların dosyalarından başvuru şikâyetleri tanı yaşları, son değerlendirme yaşları, cinsiyetleri, anne-baba arasındaki akrabalık düzeyi, kardeş ölüm öyküsü, enzim düzeyleri, genetik sonuçları değerlendirmeye alınmıştır. Hastaların son değerlendirme yaş ortalaması 17,9±18,4 yıl (dağılım 0,2-57 yıl), tanı alma yaş ortalaması 13,6±17,8 yıl (dağılım 0,1-56 yıl) olarak saptanmıştır. Sfingolipidoz tanısı ile izlediğimiz 34 hastadan 10’u (%29) Fabry hastalığı, 6’sı (%17) GM-1 gangliosidoz, 5’i (%15) metakromatik lökodistrofi, 4’ü (%12) Niemann Pick tip C, 3’ü (%9) GM-2 gangliosidoz, 2’si (%6) Gaucher, 2’si (%6) Niemann Pick tip A, 2’si (%6) Niemann Pick tip B hastalığı tanısı almıştır. Beş (%14,7) olgumuz exitus olmuştur. Olguların 21’i (%61,8) erkek, 13’ü (%38,2) kızdır. 20 (%58,8) olguda anne-baba arasında akrabalık öyküsü vardır. Hastaların tanı yaşı 1 ay ile 56 yıl arasındadır. Hastaların 15’inde (%44,1) ailede aynı hastalık tanılı birey, 8’inde (%23,5) ise kardeş ölüm öyküsü vardır. 24 (%70,5) hastada nöromotor gerilik, 11 (%32,3) hastada nöbet öyküsü vardır. Tüm olguların 13’ünde (%38,2) kardiyak tutulum, 12’sinde (%35,2) göz tutulumu vardır. Hastaların 15’inde (%44,1) hepatosplenomegali vardır. 8’i Fabry, 2’si Gaucher tanılı 10 (%29,4) hasta enzim replasman tedavisi almaktadır. Hastaların tanısı spesifik enzim düzeyleri ve genetik analiz ile kesinleştirilmiştir. Sonuç olarak, çalışmamızda Fabry hastalığı %29,4 ile en sık izlenen tiptir. Fabry tanısı ile izlenen bir hasta 5 yaşında iken göz bulgusu ile tanı almış olup, diğer hastaların tamamı erişkin yaşlarda tanı almıştır.

Anahtar Kelimeler:

sfingolipidoz, enzim replasman tedavisi, aile öyküsü.

Evaluation of the Cases We Followed with the Diagnosis of Sphingolipidosis: Single Center Experience

In this study, it was aimed to evaluate the clinical, demographic and laboratory data of the patients we followed up with the diagnosis of sphingolipidosis. Thirty-four patients who were followed up with the diagnosis of sphingolipidosis in Bursa Uludag University Faculty of Medicine, Department of Pediatric Metabolism Diseases were evaluated retrospectively. Admission complaints, age at diagnosis, last evaluation age, gender, level of consanguinity between parents, sibling death history, enzyme levels, genetic results were recorded from the files of the patients. The mean age at the last evaluation of the patients was 17.9±18.4 years (range 0.2-57 years), and the mean age at diagnosis was 13.6±17.8 years (range 0.1-56 years). Of the 34 patients we followed with the diagnosis of sphingolipidosis, 10 (29%) Fabry disease, 6 (17%) GM-1 gangliosidosis, 5 (15%) metachromatic leukodystrophy, 4 (12%) Niemann Pick type C, 3 (9%) GM-2 gangliosidosis, 2 (6%) Gaucher, 2 (6%) Niemann Pick type A, 2 (6%) Niemann Pick type B disease were detected. 5 (14.7%) of our cases were died. Of the cases, 21 (61.8%) were male and 13 (38.2%) were female. There was a history of consanguinity between the parents in 20 (58.8%) cases. The age of diagnosis of the patients was between 1 month and 56 years. Fifteen (44.1%) of the patients had a family history of the same disease, and 8 (23.5%) had a sibling death. 24 (70.5%) patients had neuromotor retardation, 11 (32.3%) patients had a history of seizures. Cardiac involvement was present in 13 (38.2%) of all cases, and ocular involvement was found in 12 (35.2%) cases. Fifteen (44.1%) patients have hepatosplenomegaly. A total of 10 patients (%29.4), 8 of whom were diagnosed with Fabry and 2 with Gaucher, were receiving enzyme replacement therapy. The diagnosis of the patients was confirmed by specific enzyme levels and genetic analysis. In conclusion, Fabry disease was the most common type with 29.4% in our study. A patient followed up with the diagnosis of Fabry was diagnosed with ocular findings when she was 5 years old, and all of the other patients were diagnosed in adulthood.

Keywords:

sphingolipidosis, enzyme replacement therapy, family history,

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1) Neufeld EF. Lysosomal storage diseases. Annu Rev Biochem. 1991;60:257-80.
2) Conzelmann E, Sandhoff K. Biochemical basis of late-onset neurolipidoses. Dev Neurosci. 1991;13(4-5):197-204.
3) Leinekugel P, Michel S, Conzelmann E, Sandhoff K. Quantitative correlation between the residual activity of beta-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease. Hum Genet. 1992 Mar;88(5):513-23.
4) Ozkara HA, Topçu M. Sphingolipidoses in Turkey. Brain Dev. 2004 Sep;26(6):363-6.
5) Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20;281(3):249-54.
6) Spada M, Pagliardini S, Yasuda M, et al, High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet. 2006 Jul;79(1):31-40.
7) Nalysnyk L, Rotella P, Simeone JC, Hamed A, Weinreb N. Gaucher disease epidemiology and natural history: a comprehensive review of the literature. Hematology. 2017 Mar;22(2):65-73.
8) Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al, International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001 Jul 5;345(1):9-16.
9) Germain DP, Waldek S, Banikazemi M, et al, Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol. 2007 May;18(5):1547-57.
10) Weidemann F, Niemann M, Breunig F, et al, Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation. 2009 Feb 3;119(4):524-9.,
11) Beck M. Treatment strategies for lysosomal storage disorders. Dev Med Child Neurol. 2018 Jan;60(1):13-18.
12) Van Dussen L, Biegstraaten M, Dijkgraaf MG, Hollak CE. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications. Orphanet J Rare Dis. 2014 Jul 24;9:112.
13) Muro S. Strategies for delivery of therapeutics into the central nervous system for treatment of lysosomal storage disorders. Drug Deliv Transl Res. 2012 Jun 1;2(3):169-86.
14) Í Dali C, Groeschel S, Moldovan M, et al, Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study. Ann Clin Transl Neurol. 2021 Jan;8(1):66-80.
15) Biffi A, Montini E, Lorioli L, et al, Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013 Aug 23;341(6148):1233158.
16) Groeschel S, Kühl JS, Bley AE, et al, Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients. JAMA Neurol. 2016 Sep 1;73(9):1133-40.