General description

Pseudo-neonatal adrenoleukodystrophy (P-NALD), also referred to as peroxisomal acyl-CoA oxidase deficiency, is caused by mutations in the ACOX1 gene located on chromosome 17q25.1. This gene encodes the peroxisomal straight-chain acyl-CoA oxidase (SCOX), which is the first and rate-limiting enzyme in the peroxisomal β-oxidation pathway. The enzyme deficiency results in impaired peroxisomal fatty acid β-oxidation and subsequent accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues.

The clinical presentation of P-NALD typically begins in the neonatal period with hypotonia and seizures as dominant features. The neonatal period may be characterized by convulsions resistant to treatment, generalized severe muscle hypotonia, feeding difficulties, and poor weight gain. Facially, approximately half of affected children exhibit dysmorphic features including hypertelorism, epicanthus, low nasal bridge, and low-set ears. Some children may present with additional features such as polydactyly and hepatomegaly. Infants born with this condition are often small for gestational age.

While psychomotor development is universally delayed, most children achieve limited developmental milestones, including the ability to walk and speak a few words. However, a characteristic feature of P-NALD is neurological regression, which typically occurs between 1-3 years of age (mean age: 28 months). During this regression phase, the initial hypotonia is replaced by hypertonia with hyperreflexia. Epilepsy may become more severe, and sensorineural hearing loss may develop. Additional neurological complications include strabismus, nystagmus, and optic atrophy.

Most children with P-NALD do not survive beyond early childhood, with a mean age of death reported as 5 years in a cohort of 22 patients. However, exceptionally mild cases with survival into adulthood have been reported, including two siblings who were diagnosed at 52 and 55 years of age.

References

1. Arora, Cheshta, et al. "Pseudo-neonatal adrenoleukodystrophy: a rare peroxisomal disorder." Annals of Indian Academy of Neurology 25.2 (2022): 275-278.