Neurodevelopmental and Cognitive Outcomes of Classical Homocystinuria: Experience from Qatar

Bashir, Haitham El; Dekair, Lubna; Mahmoud, Yasmeen; Ben‐Omran, Tawfeg

doi:10.1007/8904_2014_394

Cited by 22 publications

(19 citation statements)

References 22 publications

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“…Central nervous system: intellectual, psychiatric and behavioural problems are all common, especially in pyridoxine unresponsive patients (Abbott et al 1987; El Bashir et al 2015). Without treatment, approaching 90 % pyridoxine unresponsive patients have learning difficulties (Mudd et al 1985).…”

Section: Recommendationsmentioning

confidence: 99%

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

Morris

Kožich

Santra

et al. 2016

J of Inher Metab Disea

270

360

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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.

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Section: Recommendationsmentioning

confidence: 99%

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

Morris

Kožich

Santra

et al. 2016

J of Inher Metab Disea

270

360

View full text Add to dashboard Cite

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“…Similarly, in an earlier study utilizing healthy siblings as controls, showed that patients diagnosed by NBS had better developmental and cognitive outcomes than did those diagnosed later. 19 These results remained significant in the correlation analysis even when we adjusted for current age and age at diagnosis.…”

Section: Discussionmentioning

confidence: 83%

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

Al‐Dewik

Ali

Mahmoud

et al. 2019

J of Inher Metab Disea

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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.

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“…With a consanguinity rate of 2.38% for all metabolic conditions diagnosable by newborn screening in the IBEM-IS, we are able to provide an additional benchmark for current and future comparisons within a population ascertained by presence of recessive conditions. For comparison, previous studies from other countries have reported consanguinity rates of 5.2% for biotinidase deficiency in Brazil, 74.2% for organic acidemias in Syria, 84% for homocystinuria in Qatar, and 86.9% for 46 different metabolic disorders in Libya (AlObaidy, 2013; Borsatto et al, 2014; El Bashir, Dekair, Mahmoud, & Ben-Omran, 2015; Shennar, Al-Asmar, Kaddoura, & Al-Fahoum, 2015). Given that not all families enrolled in the IBEM-IS may be comfortable reporting consanguinity to care providers, it is possible that the 2.38% figure found in our study is an underestimate.…”

Section: Discussionmentioning

confidence: 91%

An Exploration of Genetic Test Utilization, Genetic Counseling, and Consanguinity within the Inborn Errors of Metabolism Collaborative (IBEMC)

Stein

Vockley

Edick

et al. 2017

Journal of Genetic Counseling

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The Inborn Errors of Metabolism Collaborative (IBEMC) includes clinicians from 29 institutions collecting data to enhance understanding of metabolic conditions diagnosable by newborn screening. Data collected includes hospitalizations, test results, services, and long-term outcomes. Through evaluation of this data, we sought to determine how frequently genetic counseling had been provided, how often genetic testing was performed, and also determine the consanguinity rate in this population. A data query was performed with the following elements abstracted/analyzed: current age, metabolic condition, whether genetic counseling was provided (and by whom), whether genetic testing was performed, and consanguinity. Genetic counseling was provided to families 95.8% of the time and in 68.6% of cases by a genetic counselor. Genetic testing was performed on 68.0% of subjects, with usage highest for fatty-acid-oxidation disorders (85.1%). The rate of consanguinity was 2.38%. Within this large national collaborative there is a high frequency of genetic counseling, though in one-third of cases a genetic counselor has not been involved. Additionally, while metabolic conditions have historically been diagnosed biochemically, there is currently high utilization of molecular testing suggesting DNA testing is being incorporated into diagnostic assessments - especially for fatty-acid-oxidation disorders where the underlying genotype helps predict clinical presentation.

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Neurodevelopmental and Cognitive Outcomes of Classical Homocystinuria: Experience from Qatar

Cited by 22 publications

References 22 publications

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

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

An Exploration of Genetic Test Utilization, Genetic Counseling, and Consanguinity within the Inborn Errors of Metabolism Collaborative (IBEMC)

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