Supplementary Material for: 30-year follow-up of early onset amyotrophic lateral sclerosis with a pathogenic variant in SPTLC1

Dominant mutations in serine palmitoyltransferase long chain base subunit 1 (SPTLC1), a known cause of hereditary sensory autonomic neuropathy type 1 (HSAN1), are a recently identified cause of juvenile amyotrophic lateral sclerosis (JALS) with slow progression. We present a case of SPTLC1-associated JALS followed for 30 years. She was initially evaluated at age 22 years for upper extremity weakness. She experienced gradual decline in muscle strength with development of weakness and hyperreflexia in lower extremities and diffuse fasciculations in the upper extremities at 26 years. She lost independent ambulation at age 45 years. Pulmonary function declined from a forced vital capacity of 94% predicted at 27 years to 49% predicted at 47 years, and she was hospitalized twice for respiratory failure. To our knowledge, this is the longest documented follow-up period of JALS caused by a de novo pathogenic variant in SPTLC1.

丝氨酸棕榈酰转移酶长链碱基亚基1（SPTLC1）的显性突变是遗传性感觉自主神经病1型（HSAN1）的已知致病原因，近期研究发现其亦可引发进展缓慢的青少年肌萎缩侧索硬化症（JALS）。本文报告1例SPTLC1相关JALS病例，随访时长达30年。患者于22岁时因上肢无力首次就诊，随病程进展肌力逐渐下降：26岁时出现下肢无力与反射亢进，上肢可见弥漫性肌束震颤。45岁时患者丧失独立行走能力。肺功能检查结果显示，用力肺活量预测值从27岁时的94%下降至47岁时的49%，患者曾因呼吸衰竭两次住院治疗。据我们所知，本病例是目前文献记载的SPTLC1新发致病性变异所致JALS随访时长最长的病例。