Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.

Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 µmol/L. Nevertheless, we recommend keeping the concentration below 100 µmol/L because levels fluctuate and the complications associated with high levels are so serious.

Delayed diagnosis of phenylketonuria - a case report of two siblings.

Phenylketonuria (PKU), is an autosomal recessive condition affecting the amino acid metabolism. The UK National newborn screening programme was commenced in 1969 and PKU is one among the five conditions included in the screening programme. We present the case history of two siblings of a family with a delayed diagnosis of PKU. This case history highlights such an occurrence. PKU should be considered as an important differential in the diagnosis of adult patients with learning difficulties, seizures and behavioural problems. It would be prudent to instigate plasma and urine amino/organic acid analyses in adult patients with unexplained neuropsychological manifestations.