急速に進行し，常染色体優性遺伝形式の家族性筋萎縮性側索硬化症と考えられた1家系

Familial Amyotrophic Lateral Sclerosis with Rapid Progression

要旨　発端者は41歳男性。両下肢近位部の筋力低下で発症し，筋萎縮，線維束攣縮が下肢から上肢，呼吸筋，球筋に進行した。深部腱反射は低下し，上位運動ニューロン徴候は認めなかった。髄液蛋白が軽度上昇，神経伝導検査ではM波の振幅低下とF波消失，針筋電図では急性・慢性の脱神経所見を認めた。免疫グロブリン大量静注療法（IVIg），ステロイドパルス療法（MPSL-P）を施行したが反応せず，発症3カ月で人工呼吸器管理となった。発端者の父は右上肢，従姉妹は右下肢から発症し，ともに下位運動ニューロン徴候が急速に進行し，MPSL-P，IVIg，血漿交換が行われたが反応せず，3～4カ月で人工呼吸器管理となった。常染色体優性遺伝形式の筋萎縮性側索硬化症（ALS）が疑われたが，Cu/Zn superoxide dismutase（SOD1）遺伝子の変異は認められなかった。本家系はSOD1以外の変異による家族性ALSの可能性が高いと考えられた。

We report a family with autosomal dominant （AD） motor neuron disease. A 41-year-old man developed muscle weakness and fasciculation of the lower extremities. The weakness progressed to the upper extremities and bulbar muscles. The cerebrospinal fluid （CSF） protein level was slightly elevated. A nerve conduction study revealed reduced compound muscle action potentials, but conduction block was not observed. Electromyogram showed acute and chronic neurogenic changes. He was treated with intravenous immunoglobulin （IVIg） and methylprednisolone pulse therapy, but his condition rapidly deteriorated. He developed respiratory failure necessitating artificial ventilation within three months after the onset of the disease. His father developed muscle weakness and atrophy of the upper extremities at age 70, and his cousin developed muscle weakness of the legs at age 41. Their conditions rapidly progressed to quadriplegia. CSF and electrophysiological findings were similar to those of the proband. Treatments by steroid pulse therapy, IVIg, and plasmapheresis were not effective. The father and cousin also required artificial ventilation within 3-4 months from the onset of symptoms, and became locked-in state. Autosomal dominant amyotrophic lateral sclerosis （AD-ALS） was considered, but SOD1 gene mutation was not detected. The present pedigree may have familial ALS caused by a gene mutation other than SOD1.

（Received : June 6, 2005）