Adrenoleukodystrophy

• Mosaic X-linked adrenoleukodystrophy in males identified by newborn screening and next-generation sequencing
• Blood Biomarkers Reflecting Brain Pathology-From Common Grounds to Rare Frontiers
• Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations
• Treatment of leukodystrophies: Advances and challenges
• Home-Based Rehabilitation With Frenkel's Exercises for Adrenomyeloneuropathy: A Case Report
• Adult-onset cerebral X-linked adrenoleukodystrophy presenting with frontal lobe syndrome caused by a de novo ABCD1 gene mutation (c.1415_1416delAG, p.Gln472fs*83)
• Single cell RNAseq to identify subpopulations of glial progenitors in iPSC-derived oligodendroglial lineage cultures
• Novel Pathogenic Variants in <em>POLR3K</em> Cause POLR3-Related Leukodystrophy

Adrenoleukodystrophy (ALD) is a rare, genetic disorder that primarily affects the nervous system and the adrenal glands. It belongs to a group of disorders known as leukodystrophies, which are characterized by the degeneration of the myelin sheath in the nervous system.

Here are key features of Adrenoleukodystrophy:

Genetics: ALD is caused by mutations in the ABCD1 gene, which is located on the X chromosome. As it is an X-linked disorder, it mainly affects males. Females can be carriers of the gene mutation but are usually asymptomatic.

Biochemical Basis: The ABCD1 gene encodes a protein involved in the transport of very-long-chain fatty acids (VLCFAs) into the peroxisomes, where they are broken down. Mutations in this gene lead to the accumulation of VLCFAs, particularly in the adrenal glands and the white matter of the nervous system.

Clinical Manifestations: The symptoms of ALD can vary widely, and there are different forms of the disorder. The most severe form is the childhood cerebral form, which typically presents between the ages of 4 and 10. Symptoms include behavioral changes, cognitive decline, loss of muscle control, and visual and hearing problems. Adrenal insufficiency (Addison's disease) may also occur.

Adrenal Gland Involvement: In addition to neurological symptoms, ALD often affects the adrenal glands, leading to adrenal insufficiency. This can result in fatigue, weakness, weight loss, and other symptoms related to hormonal imbalances.

Diagnostic Methods: Diagnosis is often based on clinical symptoms, family history, and biochemical testing for elevated levels of VLCFAs. Genetic testing can confirm the presence of mutations in the ABCD1 gene.

Treatment: Unfortunately, there is no cure for ALD. Treatment may involve managing symptoms and providing supportive care. Hematopoietic stem cell transplantation (HSCT) has been shown to be effective in halting the progression of cerebral ALD if performed at an early stage, before significant neurological damage has occurred.

Adrenoleukodystrophy is a complex disorder that requires a multidisciplinary approach involving neurologists, endocrinologists, and other specialists. Early diagnosis and intervention are crucial for better outcomes, particularly in cases where stem cell transplantation may be considered as a treatment option.

This case report studies a 12-year-old boy with a family history of X-linked adrenal leukodystrophy and his 8-year-old younger brother ¹⁾.

A 45-year-old Caucasian woman presented with chronic bilateral, painless, progressive, peripheral vision loss. She was found to have bilateral optic atrophy and non-enhancing multifocal white matter lesions on magnetic resonance imaging of the brain. Cerebrospinal fluid analysis showed elevated myelin basic protein. She was diagnosed as the carrier state of X-linked adrenoleukodystrophy (X-ALD). X-ALD can mimic the clinical and radiographic features of multiple sclerosis in a female carrier. This is the first case report of bilateral optic atrophy in a female X-ALD carrier in the English ophthalmic literature ²⁾.