Excellence Award Winner (Case Report Category)


Excellence Award (Case Report Category) Recipient’s Remarks

Yutaka Furuta, MD

Vanderbilt University Medical Center

I am honored to receive the Excellent Case Report Award at the American College of Physicians Japan Chapter Annual Meeting 2023. I shared a case of “A Medical Odyssey of a 72-Year-Old Man with Charcot-Marie-Tooth Disease Type 2 Newly Diagnosed with Biallelic Variants in SORD Gene Causing Sorbitol Dehydrogenase Deficiency.”

Sorbitol dehydrogenase (SORD) deficiency is characterized by a progressive neuropathy that results in limb weakness and difficulty walking. Previously, SORD deficiency (SORDD) was diagnosed symptomatically as an unknown subtype of Charcot-Marie-Tooth disease Type 2 (CMT2). However, very recently, biallelic variants in the SORD gene have been identified as the most common cause of undiagnosed cases of CMT2 (Cortese at al., Nat Genet. 2020). Patients who have been accurately diagnosed with SORDD have an opportunity to receive potential treatment with an investigational drug, govorestat that is currently being studied in a clinical trial (ClinicalTrials.gov Identifier: NCT05397665).

Our report describes a 72-year-old man who was referred to the Undiagnosed Diseases Network (UDN) suffering from gradual progressive weakness in both lower extremities since the age of 27. The patient was initially diagnosed as having CMT2 without a defined genetic cause. However, this patient was formally diagnosed with SORDD after the identification of homozygosity for the SORD frameshift (c.757delG:p.A253Qfs*27) through UDN Genome Sequencing. Then, the sorbitol level in his urine was found to be significantly elevated, which finally diagnosed him as having SORD deficiency.

The UDN is a research study funded by the National Institutes of Health (NIH) that strives to solve challenging medical mysteries. Vanderbilt University Medical Center is one of the original members participating the UDN, where I was given an opportunity to involve this exciting case during my residency. I gained an understanding of two important things from this case: (1) Next generation sequencing is a powerful tool to solve a medical odyssey. (2) The accurate diagnosis could provide an opportunity to receive potential treatment with an investigational drug in a clinical trial. This experience further motivated me to contribute to rare and undiagnosed diseases.

Last but not least, I would like to express my gratitude to Drs. John A Phillips and John H Newman, who have walked me through this case.



ACP日本支部年次総会・講演会2023 一般演題優秀賞(症例報告部門)を受賞して
ヴァンダービルト大学 古田 穣

この度は、ACP日本支部2023年次総会においてExcellent Case Report Awardをいただき、大変光栄に存じます。今回私が発表した症例は「2型シャルコーマリートュース病 (CMT2)と臨床診断されていたが、SORD遺伝子の両アレルフレームシフトバリアントにより、Sorbitol Dehydrogenase (SORD) Deficiencyと診断に至った一例」です。SORD deficiency (SORDD)は四肢の筋力低下を特徴とする疾患で、以前までCMT2の一つとして臨床診断されていました。しかし、2020年に、SORD遺伝子の両アレルバリアントによって起こり、さらにこのバリアントが最も多い原因であることが発見され、現在米国で治療薬の治験が行われています。

今回の症例では、下肢の筋力低下を主訴に、40年以上の間CMT2と臨床的に診断されていたものの遺伝的診断がつかず、米国Undiagnosed Diseases Network (UDN)に紹介されました。UDNとは、NIHのグラント資金で運営されている未診断や希少疾患を次世代シークエンサーなどの最先端技術を駆使して診断を導く米国の研究機関です。私が現在研修しているVanderbilt大学病院は、UDNに参加している病院の一角であり、幸運なことに今回の症例に携わることができました。長い間、原因が明かされなかった病態を最新の知見および技術で診断できたことは、まさに、”診断オデッセイ”と名づけるに相応しいと思って今回の演題を決めました。また、正しい診断がつくだけでなく、それにより治療の選択肢が生まれ得ることに、大きな意義を感じました。