Presentation
We speculate that there maybe a subgroup of patients who follow a chronic neurological course after a less severe paediatric presentation. [jnnp.bmj.com]
A mild conjunctival fluorescein staining was present in the LE conjunctiva in both interpalpebral areas; no signs of epithelial damage were present in the RE. A mild papillary hypertrophy was present in the upper tarsal conjunctiva in both eyes. [bmcophthalmol.biomedcentral.com]
If malnutrition is present, a comprehensive metabolic panel and CBC count are warranted. For patients presenting with a seizure, obtain a baseline serum glucose concentration and perform a lumbar puncture. [emedicine.medscape.com]
Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present. [ read more ] 11159947 AANAT susceptibility DSPS 614163 Disease susceptibility may be associated with variations affecting the gene [nectarmutation.org]
Microcephaly was present by 2 years of age. In addition, severe developmental delay was present, but she has shown slow progress without regression. [nature.com]
Entire Body System
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Disability
We describe a consanguineous Israeli Arab kindred with five males in two interrelated families with intellectual disabilities, alacrima, achalasia, and mild autonomic dysfunction. Adrenal function is normal. [ncbi.nlm.nih.gov]
Previously, biallelic mutations in GMPPA were reported to cause a disorder characterized by achalasia, alacrima, neurological deficits, and intellectual disability. [jhu.pure.elsevier.com]
disabled children with autistic traits and ocular involvement. ( 29475819 ) Pascolini G....Digilio M.C. 2018 4 Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity and Autism Spectrum Disorder without Intellectual Disability [malacards.org]
In Ireland people with an intellectual disability are identified in the national census. Moreover, a national register of people receiving or requiring intellectual disability services is maintained and updated annually. [readbyqxmd.com]
[…] for Achalasia Causes See also causal information: Causes of Alacrima Causes of Mental retardation Causes of Intellectual disabilities Causes of Achalasia Similar Topic Articles Mental retardation Intellectual disability Alacrima Achalasia • • • References [familydiagnosis.com]
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Developmental Delay
All patients had global developmental delay, a movement disorder, and hypotonia. [nature.com]
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
These patients suffer from achalasia, alacrima, short stature, developmental delay, seizures, and cerebral atrophy, but also lack adrenal insufficiency. The protein product seems to be important for an intact Golgi apparatus. [abstracts.eurospe.org]
Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. [nectarmutation.org]
People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size ( microcephaly ). [ghr.nlm.nih.gov]
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Weakness
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
On examination mild palatal weakness was noted but tendon reflexes were preserved and no firm diagnosis was made. [jnnp.bmj.com]
Most patients (72.8%) display neurological impairment, most frequently distal muscular weakness, hyperreflexia, nasal speech, and autonomic dysfunction. [abstracts.eurospe.org]
In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). [ghr.nlm.nih.gov]
Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [rarediseases.info.nih.gov]
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Feeding Difficulties
[…] system Orthostatic hypotension Abnormality of the digestive system Achalasia Dysphagia Feeding difficulties Abnormality of the endocrine system Adrenal insufficiency Abnormality ... ... [familydiagnosis.com]
It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). [ghr.nlm.nih.gov]
RESULTS: The patient presented with global developmental delay, hypotonia, autistic-like traits, mild facial dysmorphism and other features including short stature, small hands and feet, congenital heart disease and feeding difficulty... [readbyqxmd.com]
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Weight Loss
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]
Respiratoric
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Nasal Voice
She was noted to have a nasal voice as a child. She underwent a Heller’s cardiomyotomy for achalasia of the cardia aged 24. She first presented to the neurology service 10 years later with paraesthesiae in the right arm and hand. [jnnp.bmj.com]
Gastrointestinal
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Dysphagia
[…] system Orthostatic hypotension Abnormality of the digestive system Achalasia Dysphagia Feeding difficulties Abnormality of the endocrine system Adrenal insufficiency Abnormality ... ... [familydiagnosis.com]
Recognition of the syndrome presenting in adult life permits treatment of unrecognised autonomic dysfunction, adrenal insufficiency, and dysphagia. [jnnp.bmj.com]
Esophageal manometry and esophagograms eventually disclose esophageal dysmotility in almost all patients, independently of the presence of clinical dysphagia [ 21 ]. [hon.ch]
Esophageal motility tests are pertinent in patients presenting with dysphagia, food regurgitation, or both. Determine serum sodium, potassium, aldosterone, and renin levels. [emedicine.medscape.com]
613443 600662 Autosomal dominant MEFV 16p13.3 Familial Mediterranean fever, AR 249100 608107 Autosomal recessive MEFV 16p13.3 Familial Mediterranean fever, AD 134610 608107 Autosomal dominant MEGF10 5q23.2 Myopathy, areflexia, respiratory distress, and dysphagia [mnglabs.com]
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Diarrhea
Complex hereditary spastic paraplegia Complex regional pain syndrome Complex regional pain syndrome type 1 Complex regional pain syndrome type 2 Cone rod dystrophy Congenital absence/hypoplasia of thumb Congenital adrenal hyperplasia Congenital chloride diarrhea [sanfordresearch.org]
Sequencing of RPS19 gene Diamond-Blackfan anemia 6 Sanger Sequencing of RPL5 gene Diamond-Blackfan anemia 9 Sanger Sequencing of RPS10 gene Diaphanospondylodysostosis Sequencing of the BMPER gene Diaphragmatic hernia 3 Sanger Sequencing of the gene ZFPM2 Diarrhea [pentacorelab.hu]
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Failure to Thrive
[…] to thrive, global developmental delay, and liver impairment, these features are nonspecific. [nature.com]
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Loss of Appetite
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]
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Constipation
In infancy, she was noted to have global developmental delay, acquired microcephaly, bilateral exotropia, hypotonia, and constipation. [nature.com]
Cardiovascular
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Hypotension
Symptoms of Alacrima, achalasia, and mental retardation syndrome Clinical features : Imported from Human Phenotype Ontology (HPO) Abnormality of the abdomen Achalasia Dysphagia Feeding difficulties Abnormality of the cardiovascular system Orthostatic hypotension [familydiagnosis.com]
The syndrome usually presents during the first decade of life with dysphagia or severe (occasionally fatal) hypoglycaemic or hypotensive attacks, related to adrenocortical insufficiency. [jnnp.bmj.com]
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 [en.wikipedia.org]
Specific autonomic disturbances described in this syndrome include abnormal pupillary reflexes, poor heart rate variability, and orthostatic hypotension. [rarediseases.info.nih.gov]
Further investigations showed an autonomic dysfunction with postural hypotension and abnormal heart reflexes. [bmcophthalmol.biomedcentral.com]
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Orthostatic Hypotension
hypotension Abnormality of the digestive system Achalasia Dysphagia Feeding difficulties Abnormality of the endocrine system Adrenal insufficiency Abnormality ... ... [familydiagnosis.com]
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 [en.wikipedia.org]
Specific autonomic disturbances described in this syndrome include abnormal pupillary reflexes, poor heart rate variability, and orthostatic hypotension. [rarediseases.info.nih.gov]
Currently he remains ambulant but has developed dysarthria and refractory orthostatic hypotension. On examination he had dysmorphic facial features with dysarthria and nasal speech. [jnnp.bmj.com]
Musculoskeletal
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Muscle Weakness
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). [ghr.nlm.nih.gov]
Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [rarediseases.info.nih.gov]
Palatopharyngeal incompetence, sensory impairment, ataxia, and muscle weakness are among the documented findings. Histologic Findings A lacrimal gland biopsy from a child with Allgrove syndrome was examined with an electron microscope. [emedicine.medscape.com]
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Small Head
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size ( microcephaly ). [ghr.nlm.nih.gov]
Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [rarediseases.info.nih.gov]
Eyes
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Anisocoria
More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency. [genecards.org]
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]
Formal pupillometry, when available, may demonstrate anisocoria and slowed constriction velocity. Ophthalmologic evaluation for lacrimal dysfunction Ophthalmologic testing is warranted in children with Allgrove syndrome. [emedicine.medscape.com]
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Esotropia
In this study, we report a female proband with achalasia, alacrima, hypohydrosis, apparent intellectual disability, seizures, microcephaly, esotropia, and craniofacial dysmorphism. [jhu.pure.elsevier.com]
Psychiatrical
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Psychomotor Retardation
Spinocerebellar ataxia 34133190 EMC1134.610.99Cerebellar atrophy, visual impairment, and psychomotor retardation,616875 EMX2121.810.99Schizencephaly,269160 EP300205.70.990.98Colorectal cancer, somatic,114500 EP300205.70.990.98Rubinstein-Taybi syndrome [qgenomics.com]
retardation, epilepsy and craniofacial dysmorphism, 614501 PTEN PTEN hamartoma tumor syndrome CPS1 Pulmonary hypertension, neonatal, susceptibility to, 615371 PC Pyruvate carboxylase deficiency, 266150 PDHA1 Pyruvate dehydrogenase E1-alpha deficiency [gsdseq.ir]
Neurologic
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Peripheral Neuropathy
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
neuropathy Acquired von Willebrand syndrome Acral peeling skin syndrome Acromegaly Acromesomelic dysplasia Actinic prurigo Activated PIK3-delta syndromea Acute adrenal insufficiency Acute biphenotypic leukemia Acute disseminated encephalomyelitis Acute [sanfordresearch.org]
In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). [ghr.nlm.nih.gov]
Neuropathy (Andermann Syndrome) Alport Syndrome, Autosomal Recessive Antley-Bixler syndrome Argininosuccinic aciduria Arthrogryposis, Mental Retardation, & seizures Aspartylglycosaminuria Ataxia neuropathy spectrum (ANS) Ataxia with vitamin E deficiency [genpathdiagnostics.com]
Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [rarediseases.info.nih.gov]
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Dysautonomia
Affected individuals may also have dysautonomia, developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. [diseaseinfosearch.org]
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]
Hypomyelination Dihydrolipoamide dehydrogenase deficiency Dihyropyrimidine dehydrogenase deficiency Dyskeratosis Congenita, Autosomal Recessive 5 Ehlers-Danos Syndrome, Type VIIC Ethylmalonic encephalopathy Factor XI deficiency (Hemophilia C) Familial dysautonomia [genpathdiagnostics.com]
[…] hypnic myoclonus Erythromelalgia Fabry disease Facioscapulohumeral dystrophy Familial adenomatous polyposis Familial amyloid polyneuropathy Familial atypical multiple mole melanoma syndrome Familial bicuspid aortic valve Familial clubfoot due Familial dysautonomia [sanfordresearch.org]
Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 2001; 68 :753–758. 20. Edvardson S, Cinnamon Y, Jalas C, et al. Hereditary sensory autonomic neuropathy caused by a mutation in dystonin. Ann Neurol 2012; 71 :569–572. 21. [nature.com]
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Dysarthria
Currently he remains ambulant but has developed dysarthria and refractory orthostatic hypotension. On examination he had dysmorphic facial features with dysarthria and nasal speech. [jnnp.bmj.com]
People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size ( microcephaly ). [ghr.nlm.nih.gov]
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Hyperreflexia
Most patients (72.8%) display neurological impairment, most frequently distal muscular weakness, hyperreflexia, nasal speech, and autonomic dysfunction. [abstracts.eurospe.org]
The authors describe two families with two affected siblings and a further unrelated patient with typical clinical features of Allgrove’s syndrome, who exhibit signs of multisystem neurological disease including hyperreflexia, muscle wasting, dysarthria [jnnp.bmj.com]
Workup
Workup Laboratory Studies Assess adrenal function in patients with Allgrove (AAA) syndrome. [emedicine.medscape.com]
Treatment
More Symptoms of Alacrima, achalasia, and mental retardation syndrome » Diagnosis See also related information on diagnosis: Diagnosis of Achalasia Treatments See also the following treatment articles: Treatments for Intellectual disabilities Treatments [familydiagnosis.com]
CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]
There is no cure for triple A syndrome at this time; treatment typically focuses on managing individual signs and symptoms of the condition. [rarediseases.info.nih.gov]
Standard Therapies Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]
Treatment - Achalasia Addisonianism Alacrimia syndrome Resources - Achalasia Addisonianism Alacrimia syndrome [checkorphan.org]
Prognosis
Prognosis - Achalasia Addisonianism Alacrimia syndrome Not supplied. Treatment - Achalasia Addisonianism Alacrimia syndrome Resources - Achalasia Addisonianism Alacrimia syndrome [checkorphan.org]
Etiology
[…] variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay. ( 28837161 ) Ansar M....Antonarakis S.E. 2017 35 Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology [malacards.org]
Cassella RR, Brown AL, Sayre GP, Ellis H (1964) Achalasia of the esophagus: Pathologic and etiologic considerations. Ann Surg 160: 474–486 PubMed Google Scholar 4. [link.springer.com]
The etiology of the triple A syndrome remains unknown. It has been reported from different regions of the world with no ethnic predilection. Both sexes may be affected and it has never occurred in successive generations. [hon.ch]
[…] subsequently degraded by cytosolic enzymes including NGLY1. 14 To date, a single patient with NGLY1 deficiency has been reported as part of a whole-exome sequencing (WES) study focusing on the utility of this technology to detect the underlying genetic etiology [nature.com]
Epidemiology
The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). [biblioteca.phorteeducacional.com.br]
Pathophysiology
Thus, a triple-A-like syndrome can be added to the growing list of congenital disorders of glycosylation, in which dysregulation rather than mere enzyme deficiency is the basal pathophysiological mechanism. [pesquisa.bvsalud.org]
Thus, a triple-A-like syndrome can be added to the growing list of congenital disorders of glycosylation, in which dysregulation rather than mere enzyme deficiency is the basal pathophysiological mechanism. Am. J. Hum. [uniprot.org]
Renfrow & Jan Novak Nature Reviews Nephrology (2019) Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies Stéphanie [nature.com]
Prevention
Mutations in the AAAS gene prevent this protein from reaching its proper location in the cell, which may disrupt the movement of molecules. [checkorphan.org]
Although access to preventive care is an important factor toward participation, breast cancer screening rates in Canada vary despite a universal health care system. [readbyqxmd.com]
Mutations in the AAAS gene change the structure of ALADIN in different ways; however, almost all mutations prevent this protein from reaching its proper location in the nuclear envelope. [ghr.nlm.nih.gov]
S.G.M....Kalscheuer V.M. 2018 23 Prevalence of physical conditions and multimorbidity in a cohort of adults with intellectual disabilities with and without Down syndrome: cross-sectional study. ( 29431619 ) Kinnear D....Cooper S.A. 2018 24 A new therapy prevents [malacards.org]
In addition, in some cases, treatment with anticonvulsant drugs may help prevent, reduce, or control seizures potentially occurring in association with the disorder. [rarediseases.org]