Bent spine syndrome as an initial manifestation of late-onset multiple acyl-CoA dehydrogenase deficiency: a case report and literature review

Abstract

BackgroundLate-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive inherited disease of metabolic dysfunction clinically characterized by fluctuating proximal muscle weakness, excise intolerance, and dramatic riboflavin responsiveness. Dropped head syndrome can occasionally be observed in some severe patients with late-onset MADD; however, bent spine syndrome as an initial symptom had not been reported in patients with late-onset MADD.Case presentationA 46-year-old man lost the ability to hold his trunk upright, and had difficulty in raising his head, but he had no obvious symptoms of limb weakness. Meanwhile, he developed persistent numbness of limbs and lips around. Myopathological features and combined elevation of multiple acylcarnitines indicated that the axial myopathy might be caused by lipid storage myopathy. Cervical and lumbosacral MRI revealed a lot of abnormal signals diffusing along paravertebral muscles, while the abnormal signals almost disappeared after riboflavin treatment. Nerve conduction study indicated the patient suffering from predominantly sensory neuropathy and mildly motor neuropathy. Muscle pathology also demonstrated no typical neurogenic change, which was consistent with the electrophysiological findings. Causative mutations were found in the ETFDH gene.ConclusionWe report the first case of late-onset MADD with sensory neuropathy initially manifesting as bent spine syndrome and dropped head syndrome.

FUS P525L mutation causing amyotrophic lateral sclerosis and movement disorders

“…One very interesting clinical feature observed in patient with FUS mutation was a severely disabling dropped‐head syndrome, which emerged as the initial symptom in our first patient. Primary dropped‐head syndrome is usually caused by cervical extensor myopathy of unknown etiology, while secondary dropped‐head syndrome is mostly associated with motor neuron disease (Peng et al, 2015). Our patient with p.P525L mutation showed a neck pain and a significant decrease of cervical extensor muscle strength, which have not been reported in previous cases.…”

Compound heterozygous mutations in electron transfer flavoprotein dehydrogenase identified in a young Chinese woman with late-onset glutaric aciduria type II

“…In contrast, the c.920C > G (p.S307C) mutation was relatively new. The p.S307C mutation was previously reported and associated with GA II (PS1) [ 17 , 18 ]. The p.S307C mutation was located in a critical and well-established functional domain (UQ-binding domain) (PM1) [ 18 ].…”

“…The p.S307C mutation was previously reported and associated with GA II (PS1) [ 17 , 18 ]. The p.S307C mutation was located in a critical and well-established functional domain (UQ-binding domain) (PM1) [ 18 ]. Furthermore, this variant was neither found in Exome Aggregation Consortium (ExAC) nor 1000 Genomes Project (PM2).…”

“…The c.920C > G (p.S307C) mutation was previously described in only two patients. Both patients were Han Chinese, whose age of onset were much older than our patient [ 17 , 18 ]. The features of these three patients carrying the p.S307C mutation were summarized in Additional file 2 : Table S1.…”

“…One patient initially manifested as Bent spine syndrome. Both patients had limb and lip numbness, and EMG showed no sensory nerve action potential, suggesting severe sensory neuropathy besides muscle weakness [ 17 , 18 ]. However, in the current case, progressive muscle weakness was the major symptom, while sensory nerve action potential was preserved.…”