Fraser Jamie L, Vanderver Adeline, Yang Sandra, Chang Taeun, Cramp Laura, Vezina Gilbert, Lichter-Konecki Uta, Cusmano-Ozog Kristina P, Smpokou Patroula, Chapman Kimberly A, Zand Dina J
Pediatrics Residency Program, Children's National Medical Center, Washington, DC, USA; Medical Genetics Training Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Neurology, Children's National Medical Center, Washington, DC, USA.
Mol Genet Metab Rep. 2014 Feb 11;1:66-70. doi: 10.1016/j.ymgmr.2013.12.007. eCollection 2014.
We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation which resulted in an improved clinical course.
我们报告了一对患有类 Leigh 病、进行性肌张力减退、发育倒退和慢性脑病的同胞兄妹。对年幼的同胞进行全外显子组测序，发现了一个纯合的硫胺素焦磷酸激酶（TPK）突变。该患儿开始接受高剂量硫胺素、烟酸、生物素、α-硫辛酸治疗并采用生酮饮食后，神经功能有所改善，之前丧失的发育里程碑得以重新获得。由于生化和诊断参数不一致、临床死亡迅速，TPK 缺乏症的诊断较为困难，若不使用全外显子组测序，无法及时做出诊断。分子诊断使得尝试通过补充辅助因子进行饮食调整成为可能，从而改善了临床病程。
