Neurodegenerative and leukodystrophy disorders — formative SAQs

Question 1 (10 marks)

A previously well seven-year-old boy is referred for declining school performance over two months, difficulty following the ball at sport, and intermittent vomiting. An unenhanced brain MRI shows symmetric parieto-occipital white-matter change. On examination he has increased skin pigmentation and a subtle visual-field deficit. His mother asks whether the scan means a brain tumour. ^{[1] [2]}

(a) Give the most likely diagnosis, the single addition to the scan that settles the management decision, and the tool used to stage it. (4 marks) ^[2]

(b) Name two bedside or biochemical features that support the diagnosis, and explain why adrenal assessment is essential here. (3 marks) ^[2]

(c) Outline the immediate management, naming the definitive therapy and the principle that governs its timing. (3 marks) ^[3]

Model answer

The most likely diagnosis is cerebral X-linked adrenoleukodystrophy. The single addition that settles the management decision is gadolinium contrast, because the enhancing leading edge of the inflammatory phase confirms active cerebral disease - a feature that is missed on the unenhanced scan. The tool used to stage the disease and guide the transplant decision is the Loes score, a standardised severity scale for the magnetic-resonance-imaging burden, considered alongside the neurological examination. ^[2]

Two features that support the diagnosis are the symmetric parieto-occipital, splenium-based white-matter change and the increased skin pigmentation indicating adrenal insufficiency, with the biochemical confirmation provided by plasma very-long-chain fatty acids. Adrenal assessment is essential because adrenal insufficiency accompanies a substantial fraction of cerebral adrenoleukodystrophy, can be the first presentation, and untreated Addisonian crisis is fatal - so a synacthen test is performed and hydrocortisone replacement commenced if deficient, independent of the neurological treatment decision. ^[2]

The definitive therapy is allogeneic haematopoietic stem cell transplant, which halts the inflammatory demyelination by replacing the microglial lineage with donor cells. The governing principle is that transplant works only when the Loes score is still low and the neurological examination preserved - the window halts the disease before the injury becomes irreversible, which is why the case is referred urgently to a transplant service rather than watched. ^[3]