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Neurodevelopmental and Cognitive Outcomes of Classical Homocystinuria: Experience from Qatar
Haitham El Bashir1, Lubna Dekair, Yasmeen Mahmoud
1Children Rehabilitation, Department of Pediatrics, Hamad Medical Corporation, 3050, Doha, Qatar, helbashir@hmc.org.qa.
Insights
Classical homocystinuria significantly impacts cognitive and developmental outcomes in Qatari patients, with learning disabilities and lower IQs observed. Early diagnosis through newborn screening improves outcomes, highlighting the need for psychological support.
Area of Science:
- Medical Genetics
- Neurodevelopmental Disorders
- Pediatric Neurology
Background:
- Classical homocystinuria, caused by cystathionine β-synthase (CBS) deficiency, is the most prevalent monogenic disease in Qatar, affecting 1 in 1,800 births.
- The founder mutation p.R336C is responsible for nearly all CBS deficiency cases in the Qatari population.
- Untreated classical homocystinuria can lead to severe intellectual disability, multisystem complications, and premature death, with limited data on neurodevelopmental and psychological impacts in Qatari patients.
Purpose of the Study:
- To investigate the cognitive, educational, and psychological outcomes of classical homocystinuria in Qatari patients.
- To assess the neurodevelopmental impact of CBS deficiency on individuals within the Qatari population.
- To identify factors influencing outcomes in patients with classical homocystinuria.
Main Methods:
- A cohort of 32 classical homocystinuria cases and 25 sibling controls were recruited for neurodevelopmental and cognitive assessments.
- Medical records were reviewed, and clinical/educational data were collected from parents.
- Cognitive (IQ) testing was performed using the Stanford-Binet Intelligence Test (Arabic translation - 4th ed.).
Main Results:
- No significant differences were found in fine motor, expressive language, behavioral, or visual skills between cases and controls.
- Classical homocystinuria cases exhibited significantly lower total IQ scores, particularly in short-term memory, quantitative reasoning, and visual-spatial domains.
- A notable proportion of adolescent and adult cases presented with medical comorbidities, alongside behavioral and emotional problems.
Conclusions:
- Individuals with classical homocystinuria experience developmental and cognitive challenges, including learning disabilities and lower IQs compared to sibling controls.
- Adolescents and adults with the condition are more severely affected.
- Newborn screening for early diagnosis is associated with better developmental and cognitive outcomes, underscoring the importance of psychological and psychiatric referrals as standard care.
Background:
Classical homocystinuria due to cystathionine β-synthase (CBS) deficiency (OMIM 236200) is a recessively inherited condition caused by mutations in the CBS gene. The founder mutation p.R336C accounts for almost all CBS deficiency in Qatar, affecting approximately 1 in 1,800 births, making it the most prevalent monogenic disease among the Qatari population. Untreated patients can have severe intellectual disability (ID), devastating multisystem complications and premature death. Current treatment is based on pharmacology therapy and life-long methionine-restricted diet, which is difficult to maintain particularly in late diagnosed individuals. Data on the neurodevelopmental and psychological impact of the disease on outcomes among Qatari patients are generally lacking and have not been studied.
Objectives:
To examine the cognitive, educational and psychological outcomes of classical homocystinuria on Qatari patients.
Subjects And Methods:
Thirty-two cases with classical homocystinuria and 25 sibling controls were recruited to evaluate the neurodevelopmental and cognitive outcomes. We reviewed the subjects' medical record and collected pertinent clinical and educational data from parents. Stanford-Binet Intelligence Test (Arabic translation - 4th ed.) was used for cognitive (IQ) testing.
Results:
The mean age for the subjects was 11.2 years (range 0.6-29) with 56% males. The majority of cases (93%) carried the mutation (p.R336C), and parental consanguinity was 84%. There were no differences between the two groups in the fine motor, expressive language, behavioural and visual skills. However, cases have much lower total IQ particularly in the domains of short memory, quantitative reasoning and visual-spatial domains. A significant number of adolescents and adult cases had medical co-morbidities as well as behavioural and emotional problems.
Conclusion:
Individuals with classical homocystinuria have many developmental and cognitive difficulties with significant number of cases having learning disability and lower IQs (cf. sibling controls) with adolescents and adults more affected. Those diagnosed by newborn screening have better developmental and cognitive outcomes compared to late diagnosed cases. Psychological and psychiatric referrals should be part of the standard of care for those cases.
