Muscle Pathology as a Diagnostic Clue to Allgrove Syndrome

J Neuropathol Exp Neurol. 2017 May 1;76(5):337-341. doi: 10.1093/jnen/nlx016.

Abstract

Allgrove or triple A syndrome is a rare autosomal recessive disorder that can present with a variable range of multi-system manifestations, including optic atrophy, cerebellar ataxia, upper and lower motoneuron signs and various neuropathic abnormalities. These cases are a diagnostic challenge, particularly when the eponymous combination of achalasia, Addisonianism and alacrima is incomplete. Therefore, it is in the differential diagnosis for multisystem conditions and should be known to pathologists who diagnose disorders of skeletal muscle. Here, we describe new findings in skeletal muscle histology from the case of a boy of consanguineous Turkish origin whose achalasia provided the only specific clinical clue to the diagnosis. These include myocyte nuclear abnormalities with partially abnormal anti-lamin A/C immunohistochemistry and altered nuclear ultrastructure but without overt abnormalities of nuclear pore morphology. In this case, the condition was associated with a hitherto unreported c.762delC mutation in the nucleoporin gene AAAS.

Keywords: Achalasia; Allgrove syndrome; Nuclear pathology; Nuclear pore; Skeletal muscle; Triple A syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / pathology*
  • Cell Nucleus / pathology
  • Child
  • Consanguinity
  • Diagnosis, Differential
  • Esophageal Achalasia / diagnosis*
  • Esophageal Achalasia / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Muscle Cells / pathology
  • Muscle, Skeletal / pathology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nuclear Pore Complex Proteins / genetics

Substances

  • AAAS protein, human
  • Nerve Tissue Proteins
  • Nuclear Pore Complex Proteins

Supplementary concepts

  • Achalasia Addisonianism Alacrimia syndrome