Vitamin B-12 deficiency in adolescents and young adults with phenylketonuria

Following several years absence from clinical follow up, an 18-year-old female on diet therapy for phenylketonuria presented with spastic paraparesis, tremor, disorientation, slurred speech, distractibility, deteriorating mental function and megaloblastic anaemia (Hb 64 g/l mean corpuscular volume 121). Plasma phenylalanine levels were 100-600 mu mol/l for the first 18 months of life but thereafter, because of serious psyche-social factors, > 1200 mu mol/l. Her diet had strictly excluded all meats, eggs and dairy products but she had been ingesting her medical food (Lofenalac) only irregularly. Further investigation revealed a vitamin B-12 level of 65.8 pmol/l (normal 150-670). Treatment with oral B-12 quickly corrected her anaemia and there was a gradual improvement in speech, gait, tremor, disorientation and mood but mild spastic diplegia remained. This case prompted us to survey 37 adolescent and young adult phenylketonuria patients in our clinic - 28 were on diet therapy, 9 were off(age 11-35 years, mean 21.6 years, 17 males, 20 females). Those on diet were not under ideal metabolic control. Six (16%) had subnormal serum B-12 levels (< 150 pmol/l) and another six had borderline low values (150-200 pmol/l). None had specific neurological signs of subacute combined degeneration. Serum methylmalonic acid and homocysteine were not measured. On the basis of this survey we recommend that complete blood count, serum B-12, RBC folate, methylmalonic acid and homocysteine be routinely measured in adolescents and young adults with phenylketonuria.