ABSTRACT
Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented with neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction with significant central and peripheral nervous system involvement. She was later diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene identified two heterozygous mutations within exon 14 and its donor splice site (p.L430F-c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).
Subject(s)
Adrenal Insufficiency/genetics , Esophageal Achalasia/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Nuclear Pore Complex Proteins/genetics , Adrenal Insufficiency/ethnology , Adrenal Insufficiency/metabolism , Adult , Autonomic Nervous System Diseases/genetics , Autonomic Nervous System Diseases/metabolism , Autonomic Nervous System Diseases/physiopathology , DNA Mutational Analysis , Esophageal Achalasia/ethnology , Esophageal Achalasia/metabolism , Exons/genetics , Female , Genotype , Heterozygote , Humans , Italy , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/physiopathology , RNA Splice Sites/genetics , SyndromeABSTRACT
Allgrove syndrome is a rare autosomal recessive disorder characterised by childhood onset, alacrima, oesophageal achalasia, adrenocortical insufficiency, neurological and occasionally autonomic involvement. Although the disease has been associated with mutations in the ALADIN gene on chromosome 12q13, it is genetically heterogeneous. The case we report is interesting because of its onset in adulthood, long duration of disease and prominent neurological dysfunctions. After the onset of neurological abnormalities the diagnosis went unrecognised for years until the patient presented for evaluation of dysphagia. The presence of achalasia with dysphagia, adrenal insufficiency, reduced tear production, optic atrophy and peripheral motor-sensory neuropathy with axonal loss led us to clinically diagnose Allgrove syndrome even though a genetic study showed no mutations in the ALADIN gene exons. The case we report shares many clinical features with Allgrove syndrome and, even with the limitations of a single case, underlines the variability in this syndrome and the need for appropriate investigations along with a multidisciplinary approach.
Subject(s)
Adrenal Insufficiency/genetics , Chromosome Disorders/genetics , Chromosomes, Human, Pair 12 , Esophageal Achalasia/genetics , Nerve Tissue Proteins/genetics , Nuclear Pore Complex Proteins/genetics , Adrenal Insufficiency/complications , Adult , Chromosome Disorders/complications , Dry Eye Syndromes/etiology , Esophageal Achalasia/complications , Genes, Recessive , Humans , Male , MutationABSTRACT
Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.
