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Allgrove Syndrome:
Alacrima, Achalasia, and Adrenal Insufficiency
Allgrove syndrome, first described in 1978, is characterized by alacrima,
achalasia, and adrenal insufficiency. Alacrima is typically the earliest
manifestation of the condition. Early diagnosis and prompt referral to
appropriate specialists by the eye care provider can improve the
patient's chance for survival.
1) Case History
a) 9-year-old girl with persistent epitheliopathy despite maximal
medical management
b) Medical history
i) Normal pregnancy and delivery
ii) Global developmental delay noted by the age of 2
iii) Complete lack of lacrimation since birth
iv) Achalasia diagnosed and surgically treated at the age of 4
v) Older sister also diagnosed with severe alacrima and
achalasia.
vi) Genetic testing had not revealed abnormality known to be
associated with Allgrove syndrome, but complete genetic
spectrum of the disease is not currently known.
c) Ocular history
i) Mild punctate epitheliopathy noted at age 2, managed with
artificial tears
ii) Persistent epithelial defects (with neurotrophic component)
noted at age 4, managed with punctal occlusion
iii) Tonic pupils, persistent epitheliopathy noted at age 6,
managed with more aggressive lubrication
iv) Persistent epithelial defects still present at age 8, initiated
therapy with topical cyclosporine
v) Epitheliopathy persisted at age 9, at which time patient was
referred for scleral lens evaluation
2) Pertinent Findings
a) Best corrected visual acuity 20/30 OD, 20/20- OS
b) Moderate-severe epitheliopathy present
c) No significant blepharitis or Meibomian gland dysfunction
d) No posterior pole abnormalities
3) Diagnosis
a) In this case, patient had already been evaluated by geneticist,
and had been diagnosed with Allgrove syndrome
b) Congenital alacrima may also be associated with ectodermal
dysplasia
4)
5)
6)
7)
c) Congenital alacrima may present as chronic “red eye” or
conjunctivitis in infants or young children.
Diagnosis and Discussion
a) Current understanding of Allgrove syndrome
i) First described in 1978
ii) Autosomal recessive inheritance pattern
iii) Mapped to chromosome 12q13 in 1996
iv) Further localized to AAAS gene in 2000
v) Variety of phenotypic manifestations have been identified
b) Clinical findings
i) Alacrima is the earliest and most consistent sign of the
condition.
ii) Achalasia develops in 75% of patients, usually by the age of
20.
iii) Adrenal insufficiency is usually noted before puberty. If
untreated, this can lead to potentially fatal hypoglycemic or
hypotensive attacks.
iv) Autonomic dysfunction is apparent in some patient with this
condition.
Treatment and Management
i) Scleral lenses
(1) Post-lens fluid reservoir allows for maintenance of corneal
hydration
(2) Patient’s epitheliopathy resolved rapidly with application of
scleral lenses.
ii) Moisture chamber glasses
(1) Custom-fabricated moisture chamber glasses provided
refractive correction and maintained high level of
periocular humidity.
(2) Epithelial surface was maintained with moisture chamber
glasses following initial treatment with scleral lenses.
Conclusion
a) Optometrists can play a vital role in management of patients with
congenital alacrima
i) Maintenance of ocular surface integrity
ii) Appropriate referral to other providers for further systemic
evaluation and management.
Bibliography
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32 years experience of a single centre (1977-2008). Eur J
Pediatr 2010;169:1323-1328.
b) Kimber J, McLean BN, Prevett M, Hammans SR. Allgrove or 4
“A”syndrome: an autosomal recessive syndrome causing
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multisystem neurologic disease. J Neurol Neurosurg Psychiatry
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Prpic I, Juebner A, Persic M, et al. Triple A syndrome: genotype
phenotype assessment. Clin Genet 2003;63:415-417.
Nakamura K, Yoshida K, Yoshinaga T, et al. Adult or late-onset
triple A syndrome: case report and literature review. J Neurol Sci
2010;297:85-88.
Babu K, Murthy KR, Babu N, Ramesh S. Triple A syndrome with
ophthalmic manifestations in two siblings. Indian J Ophthalmol
2007;55(4):304-306.
Brooks BP, Kleta R, Caruso RC, et al. Triple-A syndrome with
prominent ophthalmic features and a novel mutation in the AAAS
gene: a case report. BMC Ophthalmology 2004;4:7