title: Classical infantile spinal muscular atrophy with SMN deficiency causes sensory neuronopathy.
abstract: OBJECTIVE
  Classic infantile spinal muscular atrophy (SMA) is believed to be a purely motor disorder, affecting neurons of the spinal anterior horn and nuclei of the lower cranial nerves. Other organ malformations or peripheral nerve involvement have been regarded as exclusion criteria for infantile SMA. Whether SMN protein deficiency can also lead to loss of sensory neurons has not been systematically addressed.
  
  
  METHODS
  The authors evaluated the sural nerve biopsies of 19 patients with infantile SMA of varying severity. The diagnosis of SMA was confirmed by the presence of a homozygous deletion of the SMN1 gene in all patients.
  
  
  RESULTS
  In seven unrelated infants with SMA type I, axonal degeneration of the sural nerve was noted. Five patients showed abnormal sensory conduction, thus prompting sural nerve biopsy. Sural nerves showed different degrees of axonal loss: fiber density ranged from 3.482 to 22.076/mm2 and was markedly reduced in four patients. There was no evidence of primary demyelination: the ratio of total myelinated fiber thickness to axon diameter (g-ratio) was normal in the patients examined. In seven patients with SMA II and five patients with SMA III, no sural nerve alterations were seen, and conduction velocity was normal. In addition to SMN1 gene deletions, homozygous NAIP gene deletions were detected in six out of seven infants with peripheral neuropathy, whereas there was no evidence of a large deletion including the multicopy markers C212 and Ag1-CA in two out of three families tested.
  
  
  CONCLUSIONS
  In this series of patients with SMA I through III who underwent sural nerve biopsy, there was significant sensory nerve pathology in severely affected patients with SMA type I, whereas there were no sensory nerve alterations clinically or morphologically in patients with milder SMA type II or III.
authors.affiliation: Institute for Human Genetics, University of Technology Aachen, Germany. srudnik-schoeneborn@ukaachen.de
authors.forename: S
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: H H
authors.initials: HH
authors.lastname: Goebel
authors.forename: W
authors.initials: W
authors.lastname: Schlote
authors.forename: S
authors.initials: S
authors.lastname: Molaian
authors.forename: H
authors.initials: H
authors.lastname: Omran
authors.forename: U
authors.initials: U
authors.lastname: Ketelsen
authors.forename: R
authors.initials: R
authors.lastname: Korinthenberg
authors.forename: D
authors.initials: D
authors.lastname: Wenzel
authors.forename: H
authors.initials: H
authors.lastname: Lauffer
authors.forename: M
authors.initials: M
authors.lastname: Kreiss-Nachtsheim
authors.forename: B
authors.initials: B
authors.lastname: Wirth
authors.forename: K
authors.initials: K
authors.lastname: Zerres
mesh_terms: D001369:Axons / Q000648:ultrastructure; D017362:Cyclic AMP Response Element-Binding Protein; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051616:Neuronal Apoptosis-Inhibitory Protein; D009475:Neurons, Afferent / Q000473:pathology*; D010641:Phenotype; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D012678:Sensation Disorders / Q000209:etiology*; D014897:Spinal Muscular Atrophies of Childhood / Q000145:classification / Q000150:complications* / Q000235:genetics; D013497:Sural Nerve / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein; D014855:Wallerian Degeneration
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein