الصفحة الرئيسية

من نحن

الأقسام

المجلة الطبية

موقع الوزارة

راسلنا

الأرشيف

 

Allgrove (4 A) Syndrome

ABSTRACT:

 This is the first reported case of Allgrove syndrome in EGH, a 9- year-old boy presented with repeated vomiting, convulsions and alteration of consciousness. 
He had no tears since birth. Examination revealed skin hyperpigmentation and autonomic neuropathy. 
Investigations showed hypoglycemia, low cortisol level and achalasia. All are consistent with Allgrove syndrome.
Although it is a rare autosomal recessive syndrome due to progressive loss of cholinergic function in all, but if left undiagnosed it will lead to a significant morbidity and even mortality which is usually due to unrecognized adrenal crisis. 
 

INTRODUCTION:

Allgrove syndrome or called 4A syndrome; achalasia-addisonianism-alacrima-autonomic neuropathy.  This syndrome is first described by Allgrove and colleagues In 1978 in 2 unrelated pairs of siblings with isolated glucocorticoid failure and achalasia of the esophagus cardia, then other cases were described with alacrima and autonomic nervous problems.

the pathology of this syndrome may be due to a progressive loss of cholinergic function throughout the body.

  It is a rare syndrome with autosomal recessive inheritance; the gene is defined as ALADIN gene located at chromosome (12q13).

The mortality is usually due to unrecognized adrenal crisis.

The most frequent initial presentation is a hypoglycemic seizure secondary to glucocorticoid deficiency. 

Other features including alacrima leading to severe keratopathy, achalasia leading to frequent vomiting and growth failure, mild mental retardation and autonomic neuropathy.

On examination the patient has a distinct facial appearance consists of a long thin face with a long philtrum, narrow upper lip, and a down-turned mouth. Conjunctival injection as a sign of alacrima if examined by slit lamp may reveal corneal ulceration. Skin examination shows hyperpigmentation and may be hyperkeratosis and fine fissuring of the palms of the hand.  

Neurologic features may be hyperreflexia, dysarthria, hypernasal speech with palatopharyngeal incompetence, and ataxia.

Lab studies usually show hypoglycemia low cortisol, high ACTH and may show anti-adrenal antibodies.

Barium study will show the achalasia and the C.T will show atrophic lacrimal glands. The treatment will include glucocorticoid replacement therapy to avoid an adrenal crisis and to allow for normal growth. Achalasia is best managed with surgical correction and alacrima needs regular artificial tears.

Effective management will diminish morbidity and mortality and allows the patient to have a normal life span.

 

CASE REPORT:

A 9-year-old male child, his first presentation to our hospital was two years back because of fever, irritability and generalized tonic clonic convulsions.

 He had past history of repeated admissions in a peripheral hospital since the age of three years because of the same complaint, according to the mother in one admission his blood sugar was reported low and since that time he was put on anticonvulsant. 

Because of red eyes he was seen by ophthalmologist and diagnosed wrongly as spring catarrh, and because of nasal speech he was seen by ENT surgeon were adenotonsellectomy was done without improvement. 

 He was born by N.S.V.D to a consanguineous parents one male sibling died at age of 4 years because of sudden loss of consciousness but the cause of death was not known.

 On examination he has growth failure as his weight and length were far below the 5th percentile.

 Vital signs were stable except for B.P which was low (80/50). He has generalized deep skin pigmentation with long thin face and red eyes, his mentality is subnormal, he has nasal speech and difficult articulation. His C.N.S examination showed generalized mild hypotonia and moderate hyper-reflexia.

His cardiovascular, respiratory and abdominal examinations were within normal. 

His investigations showed normal C.B.C, renal and hepatic functions, TSH, T4 were normal with negative anti-thyroid antibodies. his blood sugar was only 20 mg/dl, his serum cortisol was low ( 0.2 ugm/dl ), E.E.G showed paroxysmal brain discharge.

Barium study showed achalasia and C.T brain is normal there was no report about the lacrimal glands.  

The patient was referred to the pediatric surgeon and esophageal dilatation was done to improve the achalasia.

Our patient is fulfilling all the criteria of Allgrove (AAAA) Syndrome, he has adrenal insufficiency, achalasia, alacrima (absence of tears), and autonomic neuropathy.  Most cases present with classic symptoms of primary adrenal insufficiency, including hypoglycemic seizures and shock.

 Less frequently recurrent vomiting, dysphagia, and failure to thrive (achalasia). 

The diagnosis of our patient was delayed although he was admitted in a peripheral hospital with the classic presentation and treated symptomatically therefore there should be high index of suspicion as the child has growth failure, he is very thin and looks dark although his mother is white and there is history of death of one sibling at age of 4 years after loss of consciousness (could be due to adrenal crisis)  this will raise the suspicion of Addison disease or adrenal insufficiency and this was proved by the investigation results of hypoglycemia, low cortisol level but anti-adrenal antibodies were negative and ACTH was asked but not done because the kit was not available, on the other hand because the child has severe vomiting and regurgitation barium study was done and showed achalasia. 

 All of the above plus the dysmorphic features encouraged us to dig more in the history by asking the mother whether the child has tears while crying or not? ( that problem she did not mention before even to the ophthalmologist) her answer was that her child has no tears since birth, at this point ophthalmology consultation should be done to prove the alacrima  with the Schirmer test and the C.T scan which may show atrophic lacrimal glands. 

Because there was signs and symptoms related to different systems it is wise to put them all in one diagnosis.

  As our patient has Allgrove syndrome he was given hydrocortisone as a glucocorticoid replacement therapy to avoid an adrenal crisis and to allow for normal growth, he is also on anticonvulsant. 

 Now he is looking more white having no hypoglycemic attacks and generally doing well.

References:

  • Allgrove J, Clayden GS, Grant DB: Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet 1978 Jun 17.
  • Chen W, Kelly MA, Opitz-Araya X: Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 1997 Dec 12.
  • Chu ML, Berlin D, Axelrod FB: Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests. J Pediatr 1996 Jul.
  • Clark AJ, Weber A: Adrenocorticotropin insensitivity syndromes. Endocr Rev 1998 Dec.
  • Counahan R, West R: Ocular and fingertip abnormalities in isolated glucocorticoid deficiency. J Pediatr 1974 Oct.
  • Dumic M, Radica A, Jusic A: Selective ACTH insensitivity associated with autonomic nervous system disorders and sensory polyneuropathy. Eur J Pediatr 1987 Nov.
  • Bentes C, Santos-Bento M, Sa J, et al. Allgrove syndrome in adulthood. Muscle Nerve 2001; 24: 292.
  •  Kimber J, McLean BN, Prevett M, Hammans SR. Allgrove or 4 A syndrome: an autosomal recessive syndrome causing multisystem neurological disease. J Neurol Neurosurg Psychiatry 2003; 74: 654-65

Dr. Anwar El-Sheikh Khalil
Consultant pediatrician and neonatologist

European Gaza Hospital
C.A.B.P, A.M.S.F.P, D.PED

 

 

 

  وزارة الصحة - مركز المعلومات - قسم النشر الالكتروني - 2005