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Triple A Syndrome

Allgrove Syndrome


Presentation

  • We highlight the neurologic presentation of this multisystem disorder. In the presence of complex axonal neuropathy, other features of this condition should be sought.[ncbi.nlm.nih.gov]
  • When presenting in early childhood, alacrima and, possibly, achalasia are the indicative signs; in childhood and adolescence, onset is characterized by achalasia and adrenal insufficiency; while in adulthood, presentation is predominantly neurological[orpha.net]
  • Neurological and autonomic features were present in a few patients, suggesting requirement of prolonged follow-up for these patients.[ncbi.nlm.nih.gov]
  • The authors present this condition since it is easily treatable and can be fatal if undiagnosed.[ncbi.nlm.nih.gov]
Short Stature
  • A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation[ncbi.nlm.nih.gov]
  • Dermatological abnormalities such as palmoplantar hyperkeratosis as well as other signs like short stature, microcephaly and osteoporosis point to the multisystemic character of the disorder.[ncbi.nlm.nih.gov]
  • The patient, a 12-year-old boy from consanguineous parents, was referred for short stature at the age of 7 years (height: -5.4 SD score).[ncbi.nlm.nih.gov]
  • Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.[uniprot.org]
Fatigue
  • We report a 17-year-old boy presented to the endocrine clinic with delayed puberty and a 4-year's history of fatigue and muscle weakness. He had achalasia, alacrima, and skin and mucosal hyperpigmentation.[ncbi.nlm.nih.gov]
  • This report relates to two sisters, aged 8 and 12 years, who had vomiting, muscle weakness, alacrimia, excessive fatigue and dysphagia...[readbyqxmd.com]
  • The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima).[ghr.nlm.nih.gov]
  • The patient reported generalised weakness, asthenia, fatigue, anorexia and progressive hyperpigmentation of skin for 6 months.[e-enm.org]
  • Case report A 13 year-old boy was admitted for Addison’s disease, dysphagia, muscle weakness, excessive fatigue and recent onset gait ataxia. He was born by natural delivery, after an uneventful 40 week gestation.[ijponline.biomedcentral.com]
Candidiasis
  • Upper gastrointestinal endoscopy was performed and revealed esophageal candidiasis with a dilated esophagus and there was some retained residual food with a tight Lower Esophageal Sphincter (LES) suggestive of achalasia cardia.[webmedcentral.com]
Abdominal Pain
  • pains Flat feet Mild concavity of the breastbone In the mosaic form of triple X syndrome, fewer cells have the extra X chromosome, so symptoms and characteristics, when they are present, are more mild.[everydayhealth.com]
  • pain Abdominal distention Kidney inflammation (pyelonephritis) Painful bladder condition (interstitial cystitis) Bladder spasms (spastic/hyperactive bladder) Recurrent urinary tract infections Shrinking bladder Abnormal urine output (slow stream) Urinary[undiagnosed.hms.harvard.edu]
  • Nine months prior to admission to the Beijing Children's Hospital, the patient had a vomiting incident without abdominal pain or regurgitation, which lasted 5–6 days.[spandidos-publications.com]
Recurrent Diarrhea
  • We report a 2-8/12 year-old male who presented with symptoms resembling cystic fibrosis (failure to thrive, developmental delay and recurrent diarrhea) and had elevated sweat chloride concentration.[ncbi.nlm.nih.gov]
Orthostatic Hypotension
  • There may also be signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate.Hypoglycemia (low blood sugar) is[rareconnect.org]
  • ) hypotension with compensatory tachycardia, muscle weakness, ataxia, parkinsonism, and motor peripheral neuropathy.[genedx.com]
  • Specific autonomic disturbances described in this syndrome include abnormal pupillary reflexes, poor heart rate variability, and orthostatic hypotension.[rarediseases.info.nih.gov]
  • There may also be signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate. [5] Hypoglycemia (low blood sugar[ipfs.io]
Severe Osteoporosis
  • Later on, at the age of 20 years, a bone age delay of 6 years and severe osteoporosis was diagnosed.[ncbi.nlm.nih.gov]
Osteopenia
  • Reevaluation 5-35 years after introduction of 12 mg/m(2)/day hydrocortisone showed low BMD for age in two children, osteopenia in one, and osteoporosis in six adults.[ncbi.nlm.nih.gov]
Anisocoria
  • The pattern and severity of neurologic and autonomic dysfunction in Triple-A syndrome is quite variable, including hyperreflexia, impaired visual evoked potentials, optic nerve atrophy, anisocoria (unequal pupil size), abnormal sweating, postural (orthostatic[genedx.com]
  • Author Sex Adrenal Neurological Associated deficiency abnormalities pathology Allgrove M Glucocorticoid No Hyperkeratosis of the (1978) [2] palms and soles, palm creases M Glucocorticoid No Episodic anisocoria, palm creases F Glucocorticoid No Enlargement[hon.ch]
  • People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia).[ghr.nlm.nih.gov]
Blurred Vision
  • Although severe, many of these symptoms presented in all six young adult patients are often overlooked or neglected: postural hypotension with blurred vision and syncope, hyposalivation resulting with complete edentulosis, talocrular contractures with[ncbi.nlm.nih.gov]
Visual Impairment
  • Triple A syndrome is caused by mutations in the AAAS gene and is inherited in an autosomal recessive pattern. 0004322 Visual impairment Impaired vision Loss of eyesight Poor vision Last updated: 9/24/2015 Triple A syndrome is inherited in an autosomal[rarediseases.info.nih.gov]
Hyperreflexia
  • We present a 28 year-old woman with classical systemic features of triple A syndrome with prominent neurological dysfunctions/deficits, including distal muscular atrophy, progressive muscle weakness and wasting of both legs, sensibility dysfunction, hyperreflexia[ncbi.nlm.nih.gov]
  • Both patients showed delayed developmental milestones and neurological dysfunctions (motor and sensory demyelinating neuropathy, marked hyperreflexia, calves hypothrophy, pes cavus, gait disturbance) in early childhood, when erroneously diagnosed with[ncbi.nlm.nih.gov]
  • The pattern and severity of neurologic and autonomic dysfunction in Triple-A syndrome is quite variable, including hyperreflexia, impaired visual evoked potentials, optic nerve atrophy, anisocoria (unequal pupil size), abnormal sweating, postural (orthostatic[genedx.com]
  • Neurological examination was normal except for bilateral hyperreflexia without clonus. His performance at school was reported to be satisfactory. Blood hemoglobin was 10.3 g/dL, and hematocrit was 33%.[annsaudimed.net]
  • Allgrove syndrome (triple A or 4A syndrome) is a rare autosomal recessive disorder with features of adrenal insufficiency, achalasia cardia and alacrimia with or without autonomic disturbance. [2] Neurological symptoms such as hyperreflexia, dysarthria[ijaweb.org]
Babinski Sign
  • The patient was negative for meningism and positive for the Babinski sign on the right side. No abnormal gait was observed.[spandidos-publications.com]
Neglect
  • Although severe, many of these symptoms presented in all six young adult patients are often overlooked or neglected: postural hypotension with blurred vision and syncope, hyposalivation resulting with complete edentulosis, talocrular contractures with[ncbi.nlm.nih.gov]
Pyramidal Tract Signs
  • Neurological examinations at age 60 revealed limb muscle wasting and weakness with pyramidal tract signs, distal-dominant sensory disturbance, optic atrophy, and autonomic dysfunction. Alacrima was detected using Schirmer test.[ncbi.nlm.nih.gov]

Treatment

  • The optimal therapeutic regimen and duration of treatment for non-tuberculous mycobacteria lung disease is not well established.[ncbi.nlm.nih.gov]
  • Management and treatment Treatment for Triple A syndrome includes hydrocortisone substitutive therapy, esophageal dilatation or myotomy of the lower esophageal sphincter and artificial tear drops. Management of neurological features is symptomatic.[orpha.net]
  • Balloon dilatation of the esophago-gastric junction is an effective treatment, which can avoid surgical interventions.[ncbi.nlm.nih.gov]
  • The results of treatment and follow-up and genetic counseling of the families were obtained wherever feasible.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis If untreated, triple A syndrome may have a high morbidity and prognosis can be severe. The appropriate management of the disease ameliorates the prognosis significantly.[orpha.net]
  • The prognosis of persons diagnosed with triple x syndrome is good if they have parents who support them and love them unconditionally.[syndromespedia.com]

Etiology

  • INTRODUCTION: The purpose of this study is to evaluate incidence and etiology of BMD for age/osteoporosis, a possibly overlooked symptom in triple A syndrome.[ncbi.nlm.nih.gov]
  • It is still more infrequent when associated with adrenal insufficiency and alacrima, a disorder known as Allgrove's syndrome, the etiology of which remains unclear.[ncbi.nlm.nih.gov]
  • Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD.[ncbi.nlm.nih.gov]
  • Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry.[ncbi.nlm.nih.gov]
  • Etiology The disease is caused by mutations in the AAAS gene (12q13), coding for the ALADIN nuclear pore scaffolding protein. Diagnostic methods Diagnosis is based on clinical examination and adrenal function testing.[orpha.net]

Epidemiology

  • Summary Epidemiology Prevalence is unknown but less than 100 cases have been published since the first description in 1978. Clinical description The onset of Triple A syndrome varies between infancy and adulthood.[orpha.net]
  • Epidemiology Frequency Incidence is unknown, and only scattered family and case reports are noted in the literature.[emedicine.com]
Sex distribution
Age distribution

Pathophysiology

  • However, the pathophysiology of achalasia in Allgrove's syndrome remains obscure. Here we investigated the histopathology of the cardia in Allgrove's syndrome.[ncbi.nlm.nih.gov]
  • Pathophysiology No unifying pathologic features common to the 3 primary sites affected in this syndrome (esophagus, lacrimal glands, adrenal glands) are known.[emedicine.com]
  • Sullivan, TFOS DEWS II pathophysiology report, The Ocular Surface, 10.1016/j.jtos.2017.05.011, 15, 3, (438-510), (2017). Fady Hannah-Shmouni and Constantine A.[doi.org]

Prevention

  • The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.[ncbi.nlm.nih.gov]
  • Patients should be regularly tested for adrenal dysfunction to prevent life-threatening adrenal crises.[ncbi.nlm.nih.gov]
  • Sudden unexplained death was observed in siblings, and early diagnosis and treatment could help in preventing early mortality and improving the quality of life for these patients.[ncbi.nlm.nih.gov]
  • Recently it was shown that ALADIN plays a role in the import of different factors into the nucleus, which prevent the cell from DNA damage and consecutive cell death under oxidative stress.[ncbi.nlm.nih.gov]
  • Child Guidance The psychiatric, sociological and psychological study and treatment of the developing child with emphasis on preventive or prophylactic measures focused on the familial, educational and socio-environmental milieu of the child.[bioportfolio.com]

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