Posted - December 2018 in Research Highlights
Genetic test to support clinical assessment
Achalasia-Addisonianism-Alacrimia (AAA) syndrome is an autosomal recessive condition with difficulty swallowing (achalasia) primary adrenal insufficiency (addisonianism) and lack of tears (alacrimia).
It can be mistaken for complicated HSP and should be considered diagnostically if at least one of the AAA symptoms is present.
BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of rare disorders characterized by spastic paraparesis and other symptoms. Often, other diseases can mimic HSP, which may delay diagnosis and treatment.
METHODS: Whole exome sequencing was performed in families with clinically suspected HSP without a genetic diagnosis.
RESULTS: We report three patients from two families who presented with lower limb spasticity, muscular atrophy, and other neurological symptoms, who were clinically diagnosed with complicated HSP. Whole exome sequencing revealed bi-allelic AAAS nonsense mutations; one individual was homozygous for the p.(Arg478*) mutation, and two siblings were homozygous for the p.(Arg286*) mutation, leading to the diagnosis of triple A syndrome. This rare syndrome is typically characterized by a triad of symptoms: achalasia, adrenal insufficiency, and alacrima, and is often accompanied by other neurological abnormalities.
CONCLUSIONS: Our findings suggest that triple A syndrome should be suspected in complicated HSP patients without a known genetic cause, especially if at least one of the main triad of triple A syndrome symptoms is present.
SOURCE: Mol Genet Genomic Med. 2018 Oct 31. doi: 10.1002/mgg3.492. [Epub ahead of print] PMID: 30381913
© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Triple A syndrome presenting as complicated hereditary spastic paraplegia.
1 Faculty of Medicine, McGill University, Montréal, Québec, Canada.
2 Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
3 Department of Neurology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
4 Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
5 Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
6 Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada.
7 Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
8 Department of Human Genetics, McGill University, Montréal, Québec, Canada.