Long-Term Outcomes of Adult Patients with Homocystinuria before and after Newborn Screening.

Kenji Yamada,Kikumaro Aoki,Kazunori Yokoyama,Takeshi Taketani,Seiji Yamaguchi

doi:10.3390/ijns6030060

Abstract

Background: Homocystinuria (HCU) is a rare inherited metabolic disease. In Japan, newborn screening (NBS) for HCU (cystathionine β-synthase deficiency) was initiated in 1977. We compared the outcomes between patients detected by NBS (NBS group) and clinically detected patients (non-NBS group). Methods: We administered questionnaires about clinical symptoms and social conditions to 16 attending physicians of 19 adult HCU patients treated with methionine-free formula. Results: Eighteen patients (nine patients each in the NBS and non-NBS groups) participated. The frequency of patients with ocular, vascular, central nervous system, and skeletal symptoms in the NBS group was lower than that in the non-NBS group. Intellectual disability was observed in one and eight patients in the NBS and non-NBS groups, respectively. Concerning their social conditions, all patients in the NBS group were employed or still attending school, while only two patients in the non-NBS group were employed. Three of the four patients who discontinued treatment presented some symptoms, even in the NBS group. Conclusion: The social and intellectual outcomes of adult Japanese patients with HCU detected by NBS were favorable. However, even in the patients in the NBS group, some symptoms might not be preventable without continuous treatment.

Highlights

Homocystinuria (HCU) is a rare inherited metabolic disease characterized by the accumulation of homocysteine (Hcy) and its metabolites in the blood and urine [1,2]
We reported the outcomes of inborn errors of metabolism in Japanese patients, including HCU detected by newborn screening (NBS), fifteen years ago [16], to date, the long-term outcomes of HCU are unknown
10 patients underwent NBS, one of these patients failed to be diagnosed with HCU based on NBS, and the diagnosis was made after the onset of symptoms

Summary

Introduction

Homocystinuria (HCU) is a rare inherited metabolic disease characterized by the accumulation of homocysteine (Hcy) and its metabolites in the blood and urine [1,2]. HCU is classically categorized into three types depending on the specific enzymes involved in the metabolism of sulfur-containing amino acids that are deficient. The three types are as follows: (1) cystathionine β-synthase (CBS) deficiency (OMIM, 236200); (2) defect in cobalamin metabolism; (3) methylenetetrahydrofolate reductase deficiency. Methods: We administered questionnaires about clinical symptoms and social conditions to 16 attending physicians of 19 adult HCU patients treated with methionine-free formula. Results: Eighteen patients (nine patients each in the NBS and non-NBS groups) participated. Intellectual disability was observed in one and eight patients in the NBS and non-NBS groups, respectively.

Methods

Discussion

Conclusion