EARLY SPEECH DELAY AND HEPATITIS AS PRESENTING SIGNS OF HOMOCYSTINURIA

Abstract

89 Homocystinuria Type I (HCU), the most common inborn error of methionine metabolism, is usually diagnosed on the basis of classical phenotypic findings of ectopia lentis, marfanoid features, seizure disorder or mental retardation. The diagnosis of HCU is rarely made in the first five years of life unless by neonatal screening. We report a three-year-old male who was referred to hepatology clinic for elevated liver transaminases and was diagnosed with HCU based on the presentation of hepatitis and mild neurological abnormalities. The patient was generally well. He had achieved normal developmental milestones in the first year of life and his present cognitive social gross motor, fine motor, and receptive language skills were normal for age. He had however been previously diagnosed with expressive language delay and sensory integration dysfunction. The elevation of his liver enzymes had been detected during a routine screen. On physical exam the patient measured in the 95th percentile for height, weight and head circumference. He had an otherwise normal exam, including his neurological exam. Laboratory tests revealed that over a 6-month period, the patient's ALT had ranged between 77 to 173 IU/L, AST ranged between 57-88 IU/L. GGTP, bilirubin and albumin were within normal limits. Screening for hepatitis A, B, C, α-1 antitrypsin deficiency and Wilson's disease were all negative. His anti-nuclear antibody was negative and an anti-smooth muscle antibody was positive at a dilution of 1:160. Liver histology revealed microvesicular steatosis and mild periportal fibrosis. Electron microscopy of his liver tissue revealed hypertrophy of the smooth, endoplasmic reticulum and enlarged mitochondria with irregular contours, hallmarks of HCU. Amino acid studies of blood and urine were diagnostic of HCU. A trial of pyridoxine therapy was unsuccessful, however on a low methionine diet and oral betaine the patient's speech improved slightly. Conclusion: It is important to consider inborn errors of metabolism in the differential diagnosis of a patient with abnormal liver function tests and even a mild, isolated developmental delay or learning disability. In the case of HCU, early diagnosis and treatment is associated with improved clinical outcome, including higher adult IQ.