Abstract
BACKGROUND: Classical galactosemia (CG), if untreated, can be life threatening in early infancy; however, with early galactose restriction, survival has improved markedly. Despite early diagnosis and dietary exclusion, complications may ensue. This study aimed to identify risk factors for adverse outcomes in CG. METHODS: We conducted an analysis of our prospectively maintained database. Diagnosis was based on galactose-1-phosphate uridyltransferase (GALT) enzyme levels <10u/gm hemoglobin or mutation of the GALT gene. Clinical and laboratory data were retrieved from hospital electronic records and analyzed to identify potential predictors of mortality or neuro-ophthalmic morbidity (poor neurocognition, learning disability, and new-onset or persistent cataract). RESULTS: Fifty-nine CG patients presented with infantile cholestasis. Their median age of symptom onset and diagnosis was 16 (interquartile range [IQR]: 3-90) and 50 (IQR: 4-120) days, respectively. Among the 48 survivors, 41 had follow-up for ≥18 months and were analyzed for long-term outcomes. Complete liver recovery was documented in all 41 patients, with a median time to recovery of 5 months (IQR: 3-8) following diagnosis. On a lactose-free diet (LFD), 8 (19.5%) developed new-onset cataracts, and 21 (51.2%) patients had neurocognitive issues. The univariate analysis of non-survivors (n = 11) versus survivors (n = 48) identified risk factors: older age at diagnosis, high baseline Child-Turcotte-Pugh (CTP) and Pediatric End-Stage Liver Disease (PELD) scores, low serum sodium and albumin levels, and higher international normalized ratio values. In addition, refractory ascites, persistent coagulopathy at 4 weeks on LFD, and culture-positive sepsis were significantly associated risk factors in the non-survival group. No significant predictors were found for neurocognitive issues and cataract in follow-up. CONCLUSION: PELD and CTP scores at admission predict survival. Long-term neuro-ophthalmic morbidity is not associated with liver disease severity at onset in CG.