We describe the case of a 7-year-old boy who had repeated episodes of prolonged seizures without recovery of consciousness when he arrived at a rural tertiary care teaching institute hospital in Wardha, India. Detailed history of the patient revealed that the child's symptoms began with left exotropia and visual acuity changes, progressing over 6 months to cognitive decline, hearing impairment, pseudobulbar affect, and motor issues, eventually leading to school dropout. Social isolation and difficulty walking also developed as the disease advanced. MRI brain revealed diffuse white matter lesions bilaterally with raised serum ACTH levels of 5 times the normal range associated with raised levels of tetracosanoic acid (C24) and hexacosanoic acid (C26), along with elevated C24/C22 and C26/C22 ratios. The patient was provisionally diagnosed as X linked cerebral adrenoleukodystrophy. Post treatment and stabilization, the patient was seizure-free on antiepileptic medications, however, patient developed blindness, lost mobility, became bedridden, and progressed to a vegetative state within 6 months. Adrenoleukodystrophy (ALD) is a rare X-linked genetic disorder that primarily affects men. It is caused by mutations in the ABCD 1 gene and is characterized by an abnormal build-up of very long-chain fatty acids (VLCFA) in various body tissues, which affect the spinal cord, white matter, and adrenal glands, causing progressive damage and dysfunction at each location. This case highlights the importance of early diagnosis and intervention to slow down disease progression in order to improve outcome. Also, increased awareness among healthcare professionals to help early detect the signs of this disease is of great importance.

A man in his 30s presented with a 6-month history of progressive left face, arm and leg weakness. Medical history included epilepsy and vitamin B12 deficiency. Three maternal second degree relatives died before the age of 7 from various neurological disorders. Examination revealed a mild left facial droop and weakness of the left shoulder, hip and ankle. Reflexes were symmetrical and tone was normal. Differential diagnosis included glioma, subacute infarction, lymphoma and demyelination. MRI brain showed an extensive right sided subcortical white matter lesion, with extension into the brainstem. The patient's weakness progressed over 3 months. Brain biopsy showed evidence of demyelination and gliosis. A pathological diagnosis of tumefactive multiple sclerosis was made, but also rare metabolic disorders such as X-linked adrenoleukodystrophy (X-ALD) were proposed. Serum very long-chain fatty acids were significantly elevated. Genetic testing showed a mutation in the ABCD1 gene, confirming a diagnosis of X-ALD.

X-linked adrenoleukodystrophy is a severe demyelinating neurodegenerative disease mainly affecting males. The severe cerebral adrenoleukodystrophy (cALD) phenotype has a poor prognosis and underlying mechanism of onset and progression of neuropathology remains poorly understood. In this study we aim to integrate metabolomic and microRNA (miRNA) datasets to identify variances associated with cALD. Postmortem brain tissue samples from five healthy controls (CTL) and five cALD patients were utilized in this study. White matter from ALD patients was obtained from normal-appearing areas, away from lesions (NLA) and from the periphery of lesions- plaque shadow (PLS). Metabolomics was performed by gas chromatography coupled with time-of-flight mass spectrometry and miRNA expression analysis was performed by next generation sequencing (RNAseq). Principal component analysis revealed that among the three sample groups (CTL, NLA and PLS) there were 19 miRNA, including several novel miRNA, of which 17 were increased with disease severity and 2 were decreased. Untargeted metabolomics revealed 13 metabolites with disease severity-related patterns with 7 increased and 6 decreased with disease severity. Ingenuity pathway analysis of differentially altered metabolites and miRNA comparing CTL with NLA and NLA with PLS, identified several hubs of metabolite and signaling molecules and their upstream regulation by miRNA. The transomic approach to map the crosstalk between miRNA and metabolomics suggests involvement of specific molecular and metabolic pathways in cALD and offers opportunity to understand the complex underlying mechanism of disease severity in cALD.

Hematopoietic stem cell transplant (HSCT) is the only accepted treatment capable of halting the progression of X-linked cerebral adrenoleukodystrophy (CALD). While survival and neurological outcomes have been described, there is little information regarding the quality of life (QoL) of transplanted patients with CALD. This analysis is a cross-sectional study of QoL in 16 males diagnosed with CALD who underwent HSCT at a single institution. Each child or parent proxy completed subscales from the Neuro-QoL and the PROMIS Pediatric Profile Instrument representing physical, mental, and social health domains. Descriptive statistics summarized the demographic characteristics and QoL subscale T-scores, Spearman Rho correlations identified the relationships among the variables, and Mann-Whitney tests examined group differences between those with pre-HSCT Loes scores <10 and those with pre-HSCT Loes scores ≥10. The median age of respondents at the time of transplant was 8 years at HSCT (5-14) with a median of 5 years since HSCT (0.5-11). Scores from the selected QoL subscales were similar to healthy peers, though those with pre-HSCT Loes scores ≥10 had lower mobility, upper extremity function, peer interaction, and higher scores for anxiety. Although HSCT has the capability of halting progression of CALD, those with pre-HSCT Loes scores ≥10 after HSCT are at-risk for poor QoL. Longitudinal monitoring is necessary to further appreciate the factors affecting QoL among boys with CALD after HSCT, and how this may be improved.