A severily affected case with Schimke immuno osseous dysplasia

Cengiz CANDAN, Yüksel YILMAZ, Yasemin ALANAY, Pınar TURHAN, Fatma CANDAN, Müferet ERGÜVEN

Abstract

To the Editor Schimke immuno osseous dysplasia SIOD; MIM 242900 is a multi system syndrome with autosomal recessive inheritance caused by a rare mutation in chromatin remodeling protein SMARCAL 1 characterized by disproportional short stature with truncal shortness due to spondyloepiphysial dysplasia steroid resistant nephrotic syndrome progressing to end stage renal failure ESRD recurrent infections caused by cellular immune deficiency and typical phenotypic characteristics 1 2 Ischemic attacks in the brain migraine ectodernal abnormalities and hypothroidism are observed frequently in SIOD 2 3 In this article a patient who was referred with a clinical picture of steroid resistant nephrotic syndrome in the early childhood and who was diagnosed as SIOD with growth failure and typical phenotypic characteristics was presented Treatment administered to this patient who rapidly progressed to ESRD and underwent peritoneal dialysis PD and developed treatment resistant migraine attacks and severe recurrent ischemic attacks in the brain was summarized A three year old female patient was referred to our clinic because of swelling in the eyelids abdomen and legs Her personal medical history revealed that she was born from the 3rd pregnancy of a 24 year old mother as the first living baby by cesarean section at the 34th gestational week which was performed because of oligohydramniosis and intrauterine growth failure determined in the 6th month of pregnancy with a birth weight of 1780 g and a height of 46 cm The family recognized that her body weight and height were retarded compared to her peers after she was 1 5 years of age The mother and the father were double cousins On physical examination the height was found to be compatible with 4 SD and the body weight was found to be compatible with 2 4 SD The blood pressure was found to be compatible with the 95th percentile Brown discolorations with a diameter of 3 8 cm were found on the whole body especially on the groins and trunk The hair was fine the nose root was prominent and the nose had a bulleous structure Her teeth were small her neck was short and the antero posterior diameter of her chest was increased Picture 1a b Abdominal ascites and pretibial edema were present A diagnosis of nephrotic syndrome was made in the patient who had hypoalbuminemia and hyperlipidemia Since she did not respond to oral prednisolone treatment renal biopsy was performed and a diagnosis of focal segmental glomerulosclerosis FSGS was made Since no response to cyclosporine A and steroid treatment could be obtained immunsuppressive treatment was discontinued at the end of 6 months and the patient was followed up with angiotensin converting enzyme inhibitor angiotensin receptor blocker and statin treatment ESRD developed 15 months after the first diagnosis and the patient was included in PD program The patient rsquo;s blood pressure was maintained in normal ranges with dual antihypertensive drug therapy 4 months after peritoneal dialysis was started the patient developed headaches which were pulsative lasted for a few hours and recurred during the day recurring 3 4 times a day which responded to oral analgesics initially but did not respond to treatment later and gradually became more severe One month after this she presented to the emergency department with left central facial paralysis and weakness in the left lower and upper extremity An area of acute ischemia was observed in the right half of the brain on diffusion magnetic resonance MR imaging Picture 2 Low molecular weight heparin acetyl salicylic acid and levetiracetam treatment was started and the neurologic findings started to improve from the second day of treatment 5 days after the attack neurologic examination was found to be normal Digital angiographic imaging revealed 20 50 narrowing in the first segments of the anterior and middle cerebral arteries bilaterlly At this time a diagnosis of SIOD was considered in pediatric genetic consultation with the clinical findings DNA sample was planned to be obtained for molecular diagnosis Our patient had most of the dysmorphic and phenotypic characteristics described in the literature for SIOD Direct graphies revealed flattening in the vertebrae and hypoplastic pelvis Picture 3a b Total lymphocyte count was found to be 570 mm3 10 6 and CD3 34 CD3 CD4 25 and CD3 CD8 9 were found to be low but a severe clinical picture of infection was not observed The patient was discharged with levetiracetam and acetyl salicylic acid Three weeks later she presented to our hospital with acute ischemic attack in the brain It was learned that migraine type headache attacks continued at this time In the period following the second attack levetiracetam was changed with sodium valproate and enoxaparine was started again 10 days later a third ischemic attack developed and severe headaches continued After the dose of valproic acid was increased to 20 mg kg day a marked improvement was observed in migraine attacks While our patient was being followed up with this treatment without any neurologic findings she was lost following the stroke attack she had 3 months later In 50 60 of the patients with Schimke immuno osseous dysplasia a mutation in SMARCAL1 has been found 4 While some of the patients have early onset and severe disease some others have a late onset and milder disease However some early onset patients reach their mid twenties and clinical variance has been shown even in siblings 5 6 Failure to establish a relation between genotype and phenotype and clinical variance have been explained by affection of mutation in SMARCAL1 by environmental genetic and epigenetic variables and occurence of the clinical picture in patients in whom no mutation can be found has been explained by non allelic heterogeneity 7 However no difference could be found between the patients in whom mutation could be found and could not be found in terms of clinical and radiologic characteristics 8 In Schimke immuno

Özet

Schimke immün-kemik displazisi (SIOD, MIM 242900), otozomal çekinik geçişli, nadir görülen kromatin remodeling proteindeki (SMARCAL 1) mutasyonun yol açtığı spondiloepifizyel displazi nedenli gövde kısalığı ile giden orantısız boy kısalığı, son dönem böbrek yetersizliğine (SDBY) ilerleyen steroide dirençli nefrotik sendrom, hücresel immün yetersizliğe bağlı tekrarlayan enfeksiyonlar ve tipik fenotipik özellikleri ile belirgin çok sistemli bir sendromdur (1,2). Beyinde iskemik ataklar, migren, ektodermal anormallikler, hipotiroidizm SIOD’da sık görülen bulgulardır (2,3). Bu yazıda erken çocukluk döneminde steroide yanıtsız nefrotik sendrom kliniği ile başvuran, büyüme geriliği ve tipik fenotipik özellikleri ile SIOD tanısı alan bir olgu sunulmuştur. Hızla SDBY’ye ilerleyerek periton diyalizi (PD) uygulanırken, tedaviye dirençli migren atakları ve beyinde yineleyen şiddetli iskemik ataklar geliştiren olguda uygulanan tedavi özetlenmiştir.