Background: We present the first locally reported homozygous case for a pathogenic variant in the aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) gene associated with Pelizaeus-Merzbacher-like disease type II in the Philippines.It is a rare disease characterized by progressive neurological deterioration commonly presenting as nystagmus and early hypotonia evolving to spasticity with delay in achieving motor and language developmental milestones.The patient is a six-week-old female infant who presented with microcephaly, opisthotonus, inability to track objects to midline, lack of social smile to familiar voices, regurgitation, feeding difficulties, and failure to thrive, which prompted further investigation. Diagnostic imaging, including cranial MRI, revealed severe hypomyelination in multiple brain regions, supporting a diagnosis of PMLD2. The leukodystrophy and genetic leukoencephalopathy panel identified a pathogenic variant c.115C>T (p.Gln39*) in the AIMP1 gene. This gene is associated with autosomal recessive hypomyelination leukodystrophy 3 (HLD3). HLD3 is clinically similar to X-linked Pelizaeus-Merzbacher disease (PMD), hence the term Pelizaeus-Merzbacher-like disease (PMLD).Therapeutic interventions focused on symptomatic management, such as seizure control, rehabilitation therapies, and nutritional adjustments. Despite multidisciplinary efforts, the prognosis remains guarded due to its neurodegenerative nature. This case focuses on the importance of early detection and required care in managing PMLD2, emphasizing the challenges in diagnosing leukodystrophies.Case: A term female infant, born to non-consanguineous parents after an unremarkable prenatal course except for threatened abortion and treated asymptomatic bacteriuria, was delivered via normal spontaneous delivery (Apgar 9,9; BW 2.7 kg; HC 30 cm, z-score -3). Newborn and hearing screens were normal. At home, she had fair suck, regurgitation, weak cry, constipation, and intermittent generalized stiffening. At 21 days, abnormal posturing after feeds led to a diagnosis of gastroesophageal reflux, but symptoms persisted.By 6 weeks, she exhibited developmental delay—no social smile, poor visual tracking, clenched fists, persistent head tilt—and was referred for neurologic assessment. Family history revealed hypertension on both sides, no consanguinity (Figure 1).On admission, she was irritable but hemodynamically stable, severely underweight (2.7 kg; BMI 10.3; length 51 cm; HC 31 cm; all ~-3 z-scores). Neurologic exam showed scanning nystagmus, generalized spasticity, opisthotonus, hyperreflexia, and intact cranial nerves.Differentials included congenital Zika syndrome, neonatal tetanus, hypoxic-ischemic encephalopathy, kernicterus, Sandifer syndrome, and congenital neurologic disorders. These were sequentially excluded based on history, risk factors, and exam findings.CBC showed anemia (Hgb 118 u/L), lymphocytic predominance, thrombocytosis; electrolytes were normal. Chest X-ray revealed bilateral perihilar and postero-basal interstitial pneumonia. Cranial CT showed microcephaly with extensive bilateral cerebral white matter hypodensities (Figure 2).Results: MRI confirmed markedly reduced white matter volume with minimal myelination, predominantly frontal, also involving external capsules, corona radiata, pons, cerebellar white matter, and medulla (Figure 3).At 8 months, genetic testing identified a homozygous pathogenic variant in the AIMP1 gene (c.115C>T: p.Gln39*), confirming autosomal recessive hypomyelinating leukodystrophy 3 (HLD3) (Table 1).Supportive management included clonazepam for dystonia, oxygen weaning, aspiration prevention, and later nasogastric feeding for nutritional support. Despite interventions, she developed recurrent aspiration pneumonia and seizures, requiring levetiracetam. Growth failure persisted. Genetic counseling and multidisciplinary referrals were arranged.
