Saudi experience with classic homocystinuria.

BACKGROUND

Classic homocystinuria is an autosomal recessive disorder due to cystathionine ss-synthase deficiency. The clinical, radiological and neurophysiological findings of classic homocystinuria diagnosed at King Faisal Specialist Hospital and Research Centre (KFSH&RC) are presented in this report.

METHODS

Twenty-four patients (15 females and 9 males) were referred to KFSH&RC for work-up of mental retardation, seizures, thrombo-embolic episodes and dislocation of the ocular lenses.

RESULTS

The common clinical findings included ectopia lentis (20 patients), skeletal system involvement (18 patients), vascular system involvement (9 patients), and mental retardation (all patients to varying degrees). Unusual findings consisted of a patient who developed severe lower gastrointestinal bleeding, a patient with insulin-dependent diabetes mellitus, probably due to vasculopathy, and another having severe bronchiectasis, which may have been due to fibrillin disruption, and required the resection of a lobe of the lung. The parents of 21 patients were first-degree relatives, and 19 patients had one or more family members affected by the same disease. All patients had markedly elevated plasma levels of methionine. Cystathionine synthase activity in the fibroblast was measured in 25% of the patients and was deficient. Only four patients responded to pyridoxine and their methionine level decreased to almost normal range.

CONCLUSIONS

The aim of this study was to increase the awareness of this disease in the scientific and medical community, in particular in the general pediatrician working in Saudi Arabia who first encounters the clinical manifestations of the disease. Early detection through tandem mass spectrometry of blood spot screening and treatment are important, and may prevent the major complications of this disease.