Neurological and adrenal dysfunction in the adrenal insufficiency/alacrima/achalasia (3A) syndrome.

Review of 20 patients with glucocorticoid deficiency (three cases also with salt loss) associated with absent tear secretion (19 cases) and achalasia of the cardia (15 cases) revealed neurological abnormalities in 17 including hyper-reflexia, muscle weakness, dysarthria, and ataxia together with impaired intelligence and abnormal autonomic function, particularly postural hypotension. These findings indicate that significant neurological problems are common in this multisystem disorder.     

A syndrome of alacrima, achalasia, and neurologic anomalies without adrenocortical insufficiency

We describe a single case of a 2-year, 8-month-old male child with alacrima, achalasia, and neurologic anomalies and proven clinical and laboratory evidence of normal adrenocortical function. As the child was the product of a first cousin marriage, the possibility of autosomal recessive mode of inheritance was considered. Differentiation between this syndrome and other previously described associated syndromes is illustrated. This article emphasizes the presence of multisystem anomalies as described in the presence of normal suprarenal function.     

Esophageal achalasia and alacrima in siblings

Achalasia of the esophagus is a rare problem in children. It has been reported in siblings of consanguineous parents. Allgrove or AAA (triple-A) syndrome is an autosomal recessive condition associated with adrenal insufficiency, alacrima and achalasia of the oesophagus. We present two siblings with familial achalasia and alacrima treated at 3 months and 9 years respectively.     

The syndrome of achalasia of the esophagus,ACTH insensitivity and alacrima

A 7-year-old male presented with a triple A syndrome, a tirad of ACTH insensitivity, achilasia and alacrima. His clinical course is followed and the literature reviewed.     

Granulopoiesis in Shwachman's syndrome (pancreatic insufficiency and bone marrow dysfunction).

Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.     

Triglandular insufficiency in a 14-year old boy (diabetes mellitus, adrenal cortex insufficiency, hypothyrosis) (author's transl)

The article reports on a 14-year old boy who developed diabetes mellitus juvenilis when he was twelve years old. In his fourteenth year of life, an insufficiency of the adrenal cortex appeared as an additional symptom, followed half a year later by hypothyrosis. The article discusses the aetiological aspects. References are added regarding the combination of Addison's disease and diabetes mellitus in children and juveniles.     

Familial adrenocortiocotropin unresponsiveness associated With alacrima and achalasia: Biochemical and molecular studies in two siblings with clincial heterogeneity

The syndrome of familial adrenocorticotropin (ACTH) unresponsiveness is a rare form of primary adrenal insufficiency, usually without mineralocorticoid deficiency. It is characterized by elevated plasma ACTH concentration and undetectable plasma cortisol levels not responding to exogenous ACTH. Alacrima and achalasia have also been occasionally associated with adrenal insufficiency (triple A syndrome). Pathogenetic mutations have beein indentified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness. Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known. Here we report two siblings with familial ACTH unresponsiveness who were discrenant for skin pigmentation and mineralocorticoid function. In addition, achalasia and alacrima wer documented only in the older sibling. The boy, studied at the age of 2 years, was hyperpigmented, in contrast to his normally pigmented siter, studied at the age of 9 years; basal plasma -melanocyte stimulating hormone immunure-acitivity levels wer 79 and 38 pg/ml, respectively (normal <40 pg/ml). Furosemide-induced diuresis resulted in normal rises of plasma rein activity in both patients; however, plasma aldosterone levels increased only in the boy and not in his sister. Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality. Direct sequencing of the entire conding area of the ACTH receptor gene was also normal.Conclusion The syndrome of familial ACTH unresponsiveness can vary clinically and biologically within the same family. In contrast to results from some families with isolated familial ACTH unresponsiveness, the ACTH receptor gene does not appear to be the locus of the defect in this pedigree, suggesting a different molecular aetiology for the triple A syndrome which assciates adrenal insuficiency alacrima and achalasia.     

Acute adrenal insufficiency in the newborn]

Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but the neonatal screening has improved its potential severe outcome. The other causes and the various clinical presentations have been exposed, with a special reference to the salt-wasting syndrome. Among them, the severity of X-linked adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1 gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency is often unrecognised despite the risk of severe seizures and hypoglycaemia with brain damage. Finally, the hormonal diagnostic testing and the main therapeutic approach by corticosteroids have been indicated. The aim of this work is to focus the attention of paediatricians who examine a newborn because the risk of delayed diagnosis and fatal outcome may be limited if the clinical symptoms are soon recognized.     

Hepatic dysfunction in association with pancreatic insufficiency and cyclical neutropenia. Shwachman-Diamond syndrome

A patient with pancreatic insufficiency and cyclical neutropenia is described who also has evidence of hepatic dysfunction. He and 3 other patients whose findings are given emphasize the wide range of abnormalities seen in this syndrome.     

Cushing syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone

We present 2 cases of Cushing syndrome with secondary adrenal insufficiency from concomitant use of ritonavir and inhaled corticosteroids in children with human immunodeficiency virus infection. These cases highlight the need for special consideration when treatment with an inhaled/intranasal corticosteroid is indicated in children receiving antiretroviral therapy.     

Severe mitral insufficiency in mucopolysaccharidosis type III-B (Sanfilippo syndrome)

Summary A 6-year-old girl with mucopolysaccharidosis (MPS) III-B (Sanfilippo syndrome) who developed severe mitral regurgitation and congestive heart failure requiring surgery (valvuloplasty) is reported. One year after surgery the patient remains well, with marked improvement in her physical activity, and without signs of heart failure. This is only the second report of severe mitral regurgitation in MPS III, and is the first report of a successful repair (valvuloplasty) of a dysplastic mitral valve in the MPS. Mitral valvuloplasty should be considered instead of valve replacement in any MPS patient with mitral valve regurgitation requiring surgery.     

A 13-year-old female with Turner syndrome and achalasia

The most common gastrointestinal problems associated with Turner syndrome are intestinal telangiectasia, colon carcinomas, inflammatory bowel, and liver diseases. In this paper we present for the first time a 13-year-old female with 45,X karyotype associated with achalasia. As far as we know, achalasia associated with Turner syndrome has not been reported previously. The aim of this report was to point out the association of Turner syndrome and achalasia. It could be a coincidental or Turner syndrome-associated finding.     

Hepatic dysfunction in association with pancreatic insufficiency and cyclical neutropenia. Shwachman-Diamond syndrome.

A patient with pancreatic insufficiency and cyclical neutropenia is described who also has evidence of hepatic dysfunction. He and 3 other patients whose findings are given emphasize the wide range of abnormalities seen in this syndrome.