Hepatic and Extra-hepatic Outcomes of Classical Galactosemia in Infants: A Longitudinal Observational Study

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.

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).

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.

PELD and CTP scores at admission predict survival. Long-term neuro-ophthalmic morbidity is not associated with liver disease severity at onset in CG.