A Tanzanian Boy with Molecularly Confirmed X-Linked Adrenoleukodystrophy

M C J Dekker,A M Sadiq,H R Waterham,R M Mbwasi,B C Hamel,R Mc Larty,M A A P Willemsen

doi:10.1155/2019/6148425

Abstract

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with classical features, which can be also recognised in a low resource setting. It had been described in various populations across the globe, but very few cases have been reported from Africa. In a boy with features of a progressive central nervous system condition and adrenal failure, ABCD1 gene screening was performed based on a clinical history and basic radiological features which were compatible with ALD. A common ABCD1 mutation was identified in this patient, which is the first report of genetically confirmed ALD in Sub-Saharan Africa. ALD is likely under recognised in those areas where there is no neurologist. This genetic confirmation widens geographical distribution of ABCD1-associated disease, and illustrates recognisability of this disorder, even when encountered in a low-resource environment.

Highlights

X-linked adrenoleukodystrophy (ALD, OMIM #300100) is the most common peroxisomal disorder in the world [1, 2], and the most frequent genetic disorder affecting myelin present in the central and peripheral nervous system. e main biochemical abnormality is the accumulation of very long-chain fatty acids (VLCFA) in tissues and body fluids subsequent to their defective catabolism in the peroxisomes
As far as our literature search allows us to conclude, this is the first genetically confirmed ALD patient in Sub-Saharan Africa (SSA). e commonly occurring c.1534G>A (p.(Gly512Ser)) mutation has been described elsewhere, and adds to data on its panethnic occurrence. ere is a void on the map between Northern Africa and the Republic of South Africa which is likely explained by the lack of recognition and testing resources for ALD, rather than by the absence of the condition in these regions
Ere are reports on ALD or its clinical suspicion from South Africa, but cases published do not mention genetic confirmation [6–8]. e c.1534G>A (p.(Gly512Ser)) mutation causes a complete loss of function with no detection of ADLP in patient cells [10]. is specific mutation has been described before in many regions of the world especially Brazil, China, Japan, and various European countries, accounting for 32 patients in the ALD Mutation Database [11]. is dedicated database contains 22 references for this specific mutation, but no reports on African patients with this mutation are available

Summary

Introduction

X-linked adrenoleukodystrophy (ALD, OMIM #300100) is the most common peroxisomal disorder in the world [1, 2], and the most frequent genetic disorder affecting myelin present in the central and peripheral nervous system. e main biochemical abnormality is the accumulation of very long-chain fatty acids (VLCFA) in tissues and body fluids subsequent to their defective catabolism in the peroxisomes. X-linked adrenoleukodystrophy (ALD, OMIM #300100) is the most common peroxisomal disorder in the world [1, 2], and the most frequent genetic disorder affecting myelin present in the central and peripheral nervous system. Ere are two main clinical presentations, the so-called “childhood cerebral form” with (sub) acute onset, and rapidly fatal cerebral involvement in young boys (35% [4]), and the other form generally affecting young men with slowly progressive myelopathy and peripheral neuropathy (adrenomyeloneuropathy (AMN)) (40–45% [4]). Adrenal insufficiency is another clinical phenotype and can stand alone or occurs before, a er or at the same time as neurological disease (10% [4]). Mutations in ABCD1 have been described in ALD patients from populations around the world [1], but reports from

Case Report

Discussion

Figure S1

Findings

Figure S2