Evaluation of the effect of chenodeoxycholic acid treatment on skeletal system findings in patients with cerebrotendinous xanthomatosis.

AIM: The primary purpose of the present study is to evaluate the effect of chenodeoxycholic acid treatment on skeletal system findings in patients with cerebrotendinous xanthomatosis. MATERIAL AND METHODS: This retrospective study was conducted between June 2013 and December 2018 with seven patients with cerebrotendinous xanthomatosis in Cerrahpasa Medical Faculty Pediatric Nutrition and Metabolism Department. The clinical, epidemiologic, and genotypic features of the patients were reviewed in detail and the following items, especially related with skeletal system involvement, were recorded from medical data: history of a bone fracture, plasma calcium, phosphate, alkaline phosphatase and 25-hydroxy-vitamin D concentrations, bone mineral density values of the posteroanterior lumbar spine (L1-L4), and femoral neck before and after chenodeoxycholic acid treatment. RESULTS: Regarding the bone mineral metabolism, plasma calcium, phosphate, alkaline phosphatase levels were found in normal ranges in all patients. Plasma 25-hydroxy-vitamin D evaluation at the time of diagnosis showed deficiency in three patients and insufficiency in three patients. Following chenodeoxycholic acid therapy, 25-hydroxy-vitamin D deficiency persisted in only one patient, but insufficiency was observed in four patients. According to the bone mineral density assessments, four patients had Z-scores below the expected range for age both at initial examination and after chenodeoxycholic acid therapy. No significant difference was observed between plasma 25-hydroxy-vitamin D levels and bone mineral density Z-scores before or after treatment. CONCLUSION: This study elucidates the necessity of additional medical treatment as a part of chenodeoxycholic acid therapy to improve skeletal system findings in cerebrotendinous xanthomatosis.

AMAÇ: Bu çalismanin temel amaci serebrotendinöz ksantomatozis tanili hastalarda kullanilan kenodeoksikolik asit tedavisinin iskelet sistemi bulgulari üzerine olan etkisini tanimlamaktir. GEREÇ VE YÖNTEMLER: Bu geriye dönük çalismaya Haziran 2013 ve Aralik 2018 yillari arasinda Cerrahpasa Tip Fakültesi Çocuk Metabolizma ve Beslenme Bilim Dali'nda izlenen serebrotendinoz ksantomatozis tanili yedi hasta alindi. Hastalara ait klinik, epidemiyolojik ve genotipik özellikler geriye dönük incelendi ve özellikle iskelet sistemini ilgilendiren kemik kirigi öyküsü, kenodeoksikolik asit tedavisi öncesi ve sonrasinda plazma kalsiyum, fosfat, alkalen fosfataz, 25-hidroksi-vitamin D düzeyleri, posteroanterior lomber vertebra (L1-L4) ve femur boynu kemik mineral dansitelerine ait bilgiler kaydedildi. BULGULAR: Kemik mineral metabolizmasinin degerlendirilmesi açisindan ölçülen plazma kalsiyum, fosfat, alkalen fosfataz seviyeleri tüm hastalarda normal sinirlardaydi. Tani aninda yapilan plazma 25-hidroksi-vitamin D degerlendirilmesi; üç hastada eksiklik, üç hastada yetersizlik ile uyumluydu. Kenodeoksikolik asit tedavisi sonrasinda 25-hidroksi-vitamin D eksikligi bir hastada devam ederken, dört hastada yetersizlik saptandi. Kemik mineral dansitometri degerlendirmelerinde, dört hastada kemik mineral dansitesi Z-skorlarinin baslangiç aninda ve tedavi sonunda yasa göre düsük olarak devam ettigi görüldü. 25-hidroksi-vitamin D ve kemik mineral dansitometrisi Z-skorlari arasinda tedavi öncesi ve sonrasinda istatistiksel olarak anlamli farklilik izlenmedi. ÇIKARIMLAR: Bu çalismada, serebrotendinöz ksantomatozis tanili hastalarda iskelet sistemi bulgularinin iyilestirilmesi amaciyla kenodeoksikolik asit tedavisine ek olarak farkli medikal tedavilerin gerekli olabilecegi üzerinde durulmustur.

Emergence of insulin resistance following empirical glibenclamide therapy: a case report of neonatal diabetes with a recessive INS gene mutation.

BACKGROUND: As KATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonylureas, empiric therapy is a common practice for NDM patients. CASE PRESENTATION: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo- and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a KATP channel mutation. However, this empiric sulfonylurea trial did not improve the patient's glycemic control and resulted in resistance to exogenous insulin. Genetic testing identified a previously reported homozygous INS promoter mutation (c.-331C>G), which was not responsive to sulfonylurea therapy. CONCLUSIONS: In light of our results, we recommend to confirm the genetic diagnosis as soon as possible and decide on sulfonylurea treatment after a genetic diagnosis is confirmed.