# New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1
## 3 Results  
### Phenotyping of a SPTLC1-Related ALS Case with Juvenile Onset  
The male patient is the second child of healthy, non-consanguineous parents of German origin. His family history is unremarkable. The pregnancy was uneventful with normal fetal movements and spontaneous delivery at term with normal birth measurements. The patient was breastfed for 6 months and thrived well. At the age of 12 months, he was able to crawl coordinated, could sit without support, and tried to pull himself up. At the age of 18 months, he was able to walk without support. At the age of 3 years, it was recognized that he was not able to run. Due to additional problems affecting the fine motor abilities, school enrollment was delayed for one year. Speech and cognitive development remained normal. Chewing and swallowing were also normal.  
Due to a progressive proximal weakness accompanied by difficulties in rising from the floor, a diagnostic workup was performed at the age of 7 years, including magnetic resonance imaging (MRI) of the brain and of the spinal cord indicating normal results (Figure 1A,B). Edematous alterations were identified in musculus vastus medius, lateralis, and intermedius (black arrows in Figure 1C) but no fatty degenerations were detected. An MRI of the lower legs revealed no pathological alterations (Figure 1D).  
Echocardiography, standard laboratory evaluations, and a basic metabolic workup including creatine kinase indicated no abnormalities. Additionally, a muscle biopsy was performed at the age of 6 years (see below), highlighting an acute and chronic neurogenic atrophy. Based on these muscle biopsy findings, nerve conduction velocities (NCV) were investigated. However, neurography revealed normal results except for reduced right sural nerve sensory conduction velocity (23.3 m/s). The patient developed a restrictive ventilatory distress with forced vital capacity (FVC) of 53%.  
Our clinical examination at the age of 7 years revealed a generalized dystrophy with a body weight of 18.4 kg (5 kg < 3 rd percentile) and height of 130 cm (3 rd percentile). A generalized muscular atrophy and scapulae alate, scoliosis, and contractures of both knees and ankles were diagnosed. Patellar tendon reflexes were present. No tongue fasciculation, ataxia, or tremor were noticed. At this timepoint, he was able to walk 50 m. Due to the progressive disease course, he lost this ability to amulate independently at the age of 12 years, and subsequently needed a spine straightening surgery at the age of 13 years. Because of the progressive bulbar dysfunction, nutrition via percutaneous endoscopic gastrostomy (PEG) tube was needed at the same time. Since the age of 13 years, he has been using a non-invasive nocturnal ventilatory support and since the age of 15 years, he also requires the use of non-invasive ventilation during daytime via mouthpiece. At this time, the patient became part of the MYO-SEQ project [14]. His last appointment at the age of 21 years revealed tetraplegia, loss of head control, and inability to lift arms or legs against gravity--he was solely able to use his fingers to drive his wheelchair via joystick.