P2.226: An Unusual Presentation: Gait Instability & Cortisol Deficiency

Introduction: Adrenoleukodystrophy (ALD) is an X-linked progressive neurodegenerative disorder resulting from mutation in the ABCD1 gene. In 2016, the US Health and Human Services added ALD to the recommended uniform newborn screening panel. Screening for ALD is not federally mandated and is not implemented by all states, nor in many other countries. We present a unique scenario of an eight-year-old patient and recent migrant from Mexico who is diagnosed with ALD.

Case Description: An 8-year-old boy with remote history of seizures presents with one day of dizziness, ataxia and slowed/slurred speech. The family recently immigrated from Mexico one month ago, and a Spanish interpreter was used during the encounter. Prior to presentation, the patient appeared tired and was unable to walk without falling. He now appears dizzy with slurred speech, slow movements and inability to feed himself. On further history, patient had one seizure at 3 months of age, with an EEG concerning for epilepsy and was started on Levetiracetam. The patient was also prescribed Hydrocortisone for an unclear cortisol-related disorder. Physical examination revealed hypotension with BP 98/64, dry mucosa and tired appearance. Neurological examination revealed slowed speech with dysarthria, nystagmus with horizontal eye movements, dysmetria with finger-to-nose testing and truncal ataxia, with wide-based gait and unsteadiness. Urine toxicology was negative, and lab work revealed low Acetaminophen, Salicylate and Ethanol levels. The patient was admitted to the Pediatric ICU and the Neurology team was consulted and recommended an MRI Brain. Endocrinology team was consulted and recommended a morning Cortisol and ACTH level.

MRI Brain revealed bilateral symmetric confluent deep and subcortical white matter signal changes involving bilateral parieto-occipital lobes and posterior aspect of corpus callosum/splenium. Based on imaging, our patient was diagnosed with X-linked Adrenoleukodystrophy and was transferred to Neurology service for multi-disciplinary management including Endocrinology and Genetics. His lab work was consistent with adrenal insufficiency with a low morning Cortisol (3.5) and elevated ACTH (571).

Discussion: ALD results from a mutation in the ABCD1 gene, which affects transport of very long chain fatty acids (VLCFAs) resulting in their accumulation in white matter of the brain, spinal cord, adrenal cortex and testes. A leukodystrophy panel obtained for our patient revealed a pathogenic variant in ABCD1 gene, and lab work showed a VLCFA ratio higher than normal (C26/C22 Ratio).

Conclusion: The clinical presentation for ALD ranges from adrenal insufficiency to rapidly evolving, fatal neurological dysfunction. Cerebral ALD presents between 4 and 12 years of age with learning and behavior problems initially but can progress to seizures (seen in 20% of males), cortical blindness, central deafness, and the development of quadriparesis. Rate of deterioration can be variable with total disability developing by 6 months to 2 years of symptom onset.