Israel Medical Association Journal

Background: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. 

Objectives: To better localize the site of damage in neurolathyrism using advanced imaging methods. 

Methods: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts.

Results: In all patients clear activation was found in motor regions and the patients’ activity pattern was qualitatively similar to that in control subjects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in M1 was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects. 

Conclusions: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.

 

Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder.

Objectives: To perform molecular analysis of a patient with familial PPH[1] and provide her and her family with suitable genetic counseling.

Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling.

Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient.

Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.