(mentions CMT) Two siblings with triple A syndrome and novel mutation presenting

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Eur J Pediatr. 2010 Oct 8.

Two siblings with triple A syndrome and novel mutation presenting as hereditary

polyneuropathy.

Dumi & #263; M, Bariši & #263; N, Rojni & #263;-Putarek N, Kušec V, Stanimirovi & #263;

A, Koehler K, Huebner A.

Division of Endocrinology, Department of Pediatrics, University Hospital Zagreb,

Kišpati & #263;eva 12, 10 000, Zagreb, Croatia.

Abstract

The clinical and molecular data on triple A syndrome in two siblings (girl 3.5

years and boy 5.5 years at presentation) with early onset of neurological

dysfunction are described. 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 hereditary polyneuropathy, most

likely Charcot-Marie-Tooth disease.

After a severe adrenal crisis in the younger sister at the age of 3 years, the

older brother aged 5.5 years was also evaluated and latent adrenal insufficiency

was discovered. As both of the siblings had alacrima, hyperkeratosis of palms,

cutis anserina, and nasal speech, diagnosis of triple A syndrome was considered.

Sequencing of the AAAS gene detected a compound heterozygous mutation consisting

of a novel mutation p.Ser296Tyr (c.887C>A) in exon 9 and a previously described

p.Ser263Pro (c.787T>C) missense mutation in exon 8 in both siblings.

In conclusion, triple A syndrome should be considered in patients presenting

with early neurological dysfunction and developmental delay. Alacrima as the

earliest and most consistent clinical sign should be investigated by Schirmer

test. Patients should be regularly tested for adrenal dysfunction to prevent

life-threatening adrenal crises.