Teaching Case

A 7 year old male had progressive weakness, memory loss, academic deterioration, gradual milestone regression and convulsions. Investigations suggested adrenoleucodystrophy (ALD), a not so common white matter degenerative disorder with specific imaging characteristics in majority. Although many cases have been reported, a general paucity in literature remains.

A 7 year old male born of non-consanguineous parents presented with gradually progressing weakness, loss of memory and academic deterioration in school associated with gradual regression of all milestones. With normal development up to 6 years he had gradual regression of motor and mental milestones and five episodes of generalized seizures. On presentation, he was bed ridden for 3 months with decreased vision, hearing and speech.

The child was undernourished, had only skin and no mucosal hyperpigmentation. His pulse rate was normal while blood pressure was 90/60 mmHg. Developmental Quotient was 20%. Neurological assessment revealed impaired recent and remote memory, bilateral optic atrophy, deafness, spasticity in all limbs, brisk deep tendon reflexes and positive Babinski sign. Other systems were normal.
Blood WBC, DLC and haemoglobin were normal. Biochemical assessment revealed low serum sodium (120 mEq/L), high potassium (6.5mEq/L), and a low serum cortisol at 8 AM measuring 2.0 mg/dL. Other routine investigations as well as CSF analysis and nerve conduction velocity tests were normal.

CT brain showed bilateral symmetrical white matter hypodensities in temporo-parietal, occipital and periventricular regions, with relative sparing of frontal lobes and internal capsules. MRI brain delineated white matter lesions better showing involvement of temporo-parietal and occipital lobes with posterior predominance, and minimal to mild linear leading edge enhancements post gadolinium. Plasma very long chain fatty acids (VLCFA) were elevated. The amount of C 26:0 and ratios of C 24/22 and C 26/22 were higher than normal.

Based on the clinical features, CT, MRI scan findings, elevated plasma VLCFA and supported by blood biochemical parameters, a diagnosis of adrenoleucodystrophy (ALD) was confirmed in our case.

First clinical case was described by Siemerling and Creutzfeld in 1923 [1]. ALD is an X-linked recessive inherited disorder with considerable phenotypic variation [2]. The incidence of X-ALD in male is between 1:20,000 and 1:50,000 [3]. ALD is a neurodegenerative disorder, affecting the myelin of the nervous system and the adrenal cortex [4]. The basic abnormality is the accumulation of VLCFA caused by genetically deficient peroxisomal oxidation of fatty acids resulting from mutation in ALDP gene located on Xq 28 [2]. In all phenotypes development is usually normal during the first 3-4 years. In common childhood cerebral form of ALD, symptoms are first noted between 4-8 years in the form of deterioration of school performance, behaviour and memory. Pigmentation of the skin may precede the other manifestations by far. There is progressive adrenal failure, seizures, nystagmus, impaired hearing, visual disturbances and ataxia. Visual loss may be the presenting or predominant feature in ALD [5]. The condition is progressive and culminates in a few years in dementia, blindness, quadriplegia and death. The other phenotypes described are adrenomyeloneuropathy occurring later in life [3] and neonatal ALD which is inherited as autosomal recessive disorder. Chang et al have reported a case of neonatal ALD presenting with seizure at birth [6].

Low sodium and elevated potassium associated with low cortisol reflect adrenal dysfunction. Addison’s disease may be the first symptom of ALD in male [7]. High VLCFA in plasma, RBC or cultures skin fibroblast are the most specific findings [2,3]. CT or MRI provides a near definite diagnosis many times as in approximately 80% of patients imaging shows symmetric cerebral white matter lesions in periventricular white matter in posterior cerebrum, centering on splenium and peritrigonal white matter. But in 12%, the initial lesions are in the frontal areas [2]. Leading edge enhancements help diagnose progressive disease in post-gadolinium T1 sequences. Pre-natal diagnosis of affected male foetuses can be achieved by measurement of VLCFA in cultured amniocytes or chorionic villi. Early detection is desirable in order to prevent morbidity from this condition and newborn screening can be done by tandem mass spectroscopy [8].

In our patient, based on the clinical presentation and CT, MRI scan findings of brain, a white matter disease was considered strongly but a pin-point diagnosis could be made only after VLCFA estimation. The imaging findings raised the suspicion and led the way to further investigations which clinched the diagnosis.

Control of seizures, early bone marrow transplantation, reduced dietary intake of VLCFA, oral glyceryl trioleate and glyceryl trierucate are used to control the disease to some extent [2,3]. Lovastatin and 4-phenyl butyrate are being tried.

Our patient was treated conservatively with steroid and anticonvulsant. There was slight improvement in feeling of well being with resolution of hyper pigmentation without improvement in motor system. Subsequently he was lost on follow-up.