Nieprawidłowości ortopedyczne u 8-letniej pacjentki z chorobą Sanfilippo A: opis przypadku

Sanfilippo syndrome (mucopolysaccharidosis III – MPS III) is a rare genetic disease characterised by progressive neurodegeneration caused by uncontrolled lisosomal and intercellular space glycosaminoglycans (GAGs) accumulation. The disorder occurs after several years of proper child development and is related to changes in nervous, gastrointestinal, cardiovascular, respiratory, visual, auditory and musculoskeletal systems. The authors present orthopaedic abnormalities in an 8-year-old patient with Sanfilippo disease and discuss recommendation for medical intervention of skeletal deformations in patients suffering from Sanfilippo disease. Case presentation: an 8-year-old girl with Sanfilippo disease is reported on. She was diagnosed at the age of 3 when the first abnormalities were revealed. At the age of 8, when orthopaedic problems occurred the physical examination presented characteristic features of MPS such as thickened facial lines, flat base of the nose and dry, light hair. In neurological examination she presented macrocephaly, decreased axial muscle tone and increased circumferential muscle tone, independent but impaired gait pattern. Orthopaedics examination and diagnostic procedures revealed coxa vara, knee valgum and Achilles tendon contraction. Conclusion: Sanfilippo syndrome is a rare genetic – autosomal recessive – disease belonging to the group of Lysosomal Storage Disorders (LSDs). After several years after the first symptoms of the disease abnormalities in musculoskeletal system are revealed. The most common orthopaedic procedures in these patients are carpal tunnel release, trigger-finger release and hip replacement. In each case the patient`s QoL and the high risk of surgery and anaesthesia should be balanced individually.Choroba Sanfilippo A (mukopolisacharydoza III A) jest rzadką chorobą genetyczną charakteryzującą się postępującą neurodegeneracją spowodowaną wrodzonym niedoborem sulfatazy heparanu prowadzącym do niekontrolowanej akumulacji glikozaminoglikanów (siarczanu heparanu) w przestrzeni lizosomalnej i międzykomórkowej. Zaburzenie pojawia się po kilku latach prawidłowego rozwoju dziecka i jest związane ze zmianami w układzie nerwowym, żołądkowo-jelitowym, sercowo-naczyniowym, oddechowym, wzrokowym, słuchowym i mięśniowo-szkieletowym. Autorzy przedstawiają nieprawidłowości ortopedyczne u 8-letniej pacjentki z chorobą Sanfilippo A i omawiają rekomendacje dotyczące ortopedycznego leczenia deformacji szkieletowych w tej jednostce chorobowej. Prezentacja przypadku: Autorzy opisują 8-letnią dziewczynkę z chorobą Sanfilippo A, u której w wieku 3 lat ujawniły się pierwsze symptomy choroby. W wieku 8 lat, kiedy zaczęły się objawy ortopedyczne, w badaniu fizykalnym stwierdzano charakterystyczne dla mukopolisacharydozy cechy t.j.: pogrubiałe rysy twarzy, płaską nasadę nosa i suche, jasne włosy. W badaniu neurologicznym pacjentka prezentowała wielkogłowie, obniżone napięcie w osi głowa-tułów, a wzmożone w kończynach, chód samodzielny w nieprawidłowym wzorcu. Badanie ortopedyczne i badania dodatkowe ujawniły szpotawość stawów biodrowych, koślawość stawów kolanowych oraz tendencję do przykurczu ścięgien Achillesa. Wnioski: Choroba Sanfilippo A jest rzadką chorobą genetyczną – autosomalną recesywną – należącą do grupy lizosomalnych chorób spichrzeniowych. Po kilku latach od pierwszych objawów choroby ujawniają się nieprawidłowości w układzie mięśniowo-szkieletowym. Najczęstsze zabiegi ortopedyczne w tej grupie pacjentów to uwolnienie cieśni nadgarstka i endoprotezowanie stawu biodrowego. W każdym przypadku należy indywidualnie rozważyć korzyści przekładające się na jakość życia chorego biorąc pod uwagę wysokie czynniki ryzyka podejmowanych interwencji operacyjnych i znieczulenia

Dramatic Course of Paediatric Cryptogenic Febrile Infection-Related Epilepsy Syndrome with Unusual Chronic Phase Presentation—A Case Report with Literature Study

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic, extremely rare epileptic encephalopathy. It strikes previously healthy school-aged children and is usually cryptogenic. Its dramatic onset with refractory status epilepticus is always preceded by a nonspecific febrile illness. The seizure activity in FIRES may last for several weeks with little to no response to antiepileptic treatment, usually resulting in the usage of anaesthetics. This acute phase is followed by a chronic, refractory epilepsy and cognitive deficit, that persist for the rest of the patient’s life. Still to this day no definite cause has been described. In this study we review the current finding in FIRES and describe a case of a 4-year-old patient with a dramatic course of the acute phase in FIRES and unusual presentation of the chronic phase, which is dominated by extrapyramidal symptoms such as dystonia. This case highlights that the clinical presentation of FIRES may differ from those frequently described in literature

Nusinersen treatment of Spinal Muscular Atrophy Type 1 — results of expanded access programme in Poland

Aim of the study. This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1. Clinical rationale of study. Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. Materials and methods. We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18–26 months of treatment were compared to baseline. Results. We analysed data from 26 patients with SMA type 1, mean age 4.79 (2–15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified. Conclusions and clinical implications. Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status