Vitamin B12 deficiency in adolescents and young adults with phenylketonuria

Abstract

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 64g/l mean corpuscular volume 121). Plasma phenylalanine levels were 100-600 mumol/l for the first 18 months of life but thereafter, because of serious psycho-social factors, > 1200 mumol/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 B12 level of 65.8 pmol/l (normal 150-670). Treatment with oral B12 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 B12 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 B12, RBC folate, methylmalonic acid and homocysteine be routinely measured in adolescents and young adults with phenylketonuria.

Brain MRI Abnormalities in Phenylketonuria

“…The results of the volumetric measurements are summarized in Table 1. These findings of Pfaendner et al [13] are in accordance with other, nonquantitative imaging studies [8,[16][17][18][19]. However, it has not been previously reported that the size of the hippocampus is reduced in PKU.…”

Neurological outcome in adult patients with early-treated phenylketonuria

“…In our study, patients with very strict long-term diet did not show speci®c neurological impairment either. Vitamin B 12 de®ciency was also discussed as a possible cause of neurological impairment in adults with PKU [11]. In our study, vitamin B 12 de®ciency could be excluded in a subsample of seven patients with tremor by normal concentrations of plasma vitamin B 12 and urinary methylmalonic acid.…”

Haematological findings in children with inborn errors of metabolism

“…Hanley and colleagues reported that 6 (16%) out of 37 adolescent and young adult PKU patients had subnormal serum vitamin B 12 concentrations. They recommend that complete blood count, serum vitamin B 12 , and RBC folate concentrations be routinely measured in adolescents and young adults with PKU (Hanley et al 1996). Early assessment and therapy of iron deficiency may improve cognitive and behavioural outcomes of children with PKU (Acosta et al 2004).…”