X-linked adrenoleukodystrophy (X-ALD) is a group of peroxisomal disorders characterized by an impaired beta-oxidation of very long chain fatty acids. This defect results in an extremely variable phenotype including presymptomatic form, isolated adrenal insufficiency and cerebral disease. An incidence of about 1: 10000 male subjects has been reported(1).

Two brothers (8 years and 5 years old), born of a non-consanguineous marriage were brought with complaints of progressively increasing pigmentation and darkening of skin, starting from face since the age of 4 years. There was history of recurrent episodes of loose motions, vomiting and fever after the age of 4 years in the elder sibling for which he was hospitalized in a state of shock. Family history, perinatal history and developmental history were non-contributory. General and systemic examinations were unremarkable except for the generalized hyperpigmentation of the skin. Black colored spots were also noted on the tongue and oral mucosa.

Investigations revealed a normal hemo-gram. Basal serum cortisol levels were low [1.82 µg/dL and 2.8 µg/dL (normal= 9-25 µg/dL)] and response to ACTH was subnormal [5.86 µg/dL and 6.7µg/dL after ACTH sti-mulation test.]. Serum electrolytes, albumin, alkaline phosphatase, calcium and phos-phorus levels were normal. Thyroid function tests and antimicrosomal antibodies were negative. All these investigations suggested a primary hypofunction of adrenal glands. An abdominal ultrasound and chest X-ray were unrevealing.

The siblings were further investigated for a possibility of adrenoleukodystrophy (ALD) by estimating plasma levels of very long chain fatty acids (VLCFAs). The pattern of increase in VLCFAs levels was consistent with X-ALD (Table I). An MRI scan of brain was normal. The sibs are currently receiving replacement doses of corticosteroids with an adequate stress cover and are under continuous follow up. They have not developed any neurological complaints till now so they may be rare entities of "Addison only" variant of ALD.

C 26: 0

Sib A: 1.47
Sib B: 2.04

0.24 ± 0.14

1.30 ± 0.45

0.68 ± 0.29

C 24/22

Sib A: 1.98
Sib B: 2.14

0.78 ± 0.1

1.71± 0.23

1.30 ± 0.19

C26/22

Sib A: 0.13
Sib B: 0.16

0.01 ± 0.003

0.07 ± 0.03

0.04 ± 0.02

Majority of cases of primary adrenal insufficiency have autoimmune or tubercular etiologies but X-ALD is now being recognized as not an uncommon cause of adrenal insufficiency in males, especially in children and young adults. Many of these patients who have clinical features of only Addison disease at the time of presentation, go on developing neurological manifestations of X-ALD in future, but this interim period is highly variable and may extend up to 32 years(2-5).

Although establishing X-ALD as a cause of adrenal insufficiency doesn’t affect the endocrinal management of the patient, it opens the possibility of therapy before the onset of overt neurological disease, since both bone marrow transplantation and Lorenzo oil are beneficial only at an early stage of disease(2,5). It also allows screening of other male members and relatives who may be at risk of developing Addison disease or neurological complications. Early diagnosis also brings the possibility of genetic counseling; carrier detection and antenatal diagnosis and thus has the potential for radically reducing the incidence of this devastating disease.

N. Mehta,
P. Parekh,
Department of Pediatrics,
M.G.M. Medical College,
Indore 452 001, India.
E- mail: [email protected]