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. 2019 Sep;42(5):818-830.
doi: 10.1002/jimd.12099. Epub 2019 May 8.

Natural history, with clinical, biochemical, and molecular characterization of classical homocystinuria in the Qatari population

Nader Al-Dewik  1   2 , Alaa Ali  1 , Yassmin Mahmoud  3 , Noora Shahbeck  1 , Rehab Ali  1 , Laila Mahmoud  1 , Mariam Al-Mureikhi  1 , Fatma Al-Mesaifri  1 , Sara Musa  1 , Karen El-Akouri  1 , Mariam Almulla  1 , Reem Al Saadi  4 , Gheyath K Nasrallah  5 , Muthanna Samara  6 , Ghassan Abdoh  7 , Hilal Al Rifai  7 , Johannes Häberle  8 , Beat Thöny  8 , Warren Kruger  9 , Henk J Blom  10 , Tawfeg Ben-Omran  1   11   12
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Free article

Natural history, with clinical, biochemical, and molecular characterization of classical homocystinuria in the Qatari population

Nader Al-Dewik et al. J Inherit Metab Dis. 2019 Sep.
Free article

Abstract

Classical homocystinuria (HCU) is the most common inborn error of metabolism in Qatar, with an incidence of 1:1800, and is caused by the Qatari founder p.R336C mutation in the CBS gene. This study describes the natural history and clinical manifestations of HCU in the Qatari population. A single center study was performed between 2016 and 2017 in 126 Qatari patients, from 82 families. Detailed clinical and biochemical data were collected, and Stanford-Binet intelligence, quality of life and adherence to treatment assessments were conducted prospectively. Patients were assigned to one of three groups, according to the mode of diagnosis: (a) late diagnosis group (LDG), (b) family screening group (FSG), and (c) newborn screening group (NSG). Of the 126 patients, 69 (55%) were in the LDG, 44 (35%) in the NSG, and 13 (10%) in the FSG. The leading factors for diagnosis in the LDG were ocular manifestations (49%), neurological manifestations (45%), thromboembolic events (4%), and hyperactivity and behavioral changes (1%). Both FSG and NSG groups were asymptomatic at time of diagnosis. NSG had significantly higher intelligence quotient, quality of life, and adherence values compared with the LDG. The LDG and FSG had significantly higher methionine levels than the NSG. The LDG also had significantly higher total homocysteine levels than the NSG and FSG. Regression analysis confirmed these results even when adjusting for age at diagnosis, current age, or adherence. These findings increase the understanding of the natural history of HCU and highlight the importance of early diagnosis and treatment. SYNOPSIS: A study in 126 Qatari patients with HCU, including biochemical, clinical, and other key assessments, reveals that patients with a late clinical diagnosis have a poorer outcome, hereby highlighting the importance of early diagnosis and treatment.

Keywords: Qatar; classical homocystinuria; consanguinity; founder mutation p.R336C CBS gene; natural history.

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References

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