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Growth failure, encephalopathy, and endocrine dysfunctions in two siblings, one with 5-oxoprolinase deficiency
L H Cohen1, E Vamos, C Heinrichs
1Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
Insights
This study describes a novel autosomal recessive disorder in siblings with severe growth failure and developmental issues. The elder sibling showed 5-oxoprolinase deficiency, but the younger did not, indicating distinct conditions.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Consanguineous parents presented two female siblings with a complex phenotype.
- Symptoms included severe growth and developmental failure, dysmorphic features, endocrine dysfunction, and autistic traits.
Observation:
- The elder sibling exhibited high urinary 5-oxoproline excretion and deficient leucocyte 5-oxoprolinase activity.
- The younger sibling had normal urinary organic acid profiles.
- Clinical and biochemical evaluations excluded Rett syndrome, Dubowitz syndrome, and carbohydrate-deficient glycoprotein syndromes.
Findings:
- The siblings suffer from a previously undescribed autosomal recessive disorder.
- The disorder is distinct from the elder sibling's 5-oxoprolinase deficiency.
- 5-oxoprolinase deficiency is not associated with a distinct morbid phenotype.
Implications:
- This research identifies a new genetic disorder affecting growth and development.
- Understanding this condition expands knowledge of metabolic and genetic diseases.
- Further research is needed to elucidate the genetic basis and precise mechanisms of this novel disorder.
Unlabelled:
Two female siblings, born to consanguineous parents, presented with a similar phenotype characterized by severe growth and developmental failure, dysmorphic features, thyroid and gonadal dysfunction, autistic traits and hand stereotypes resembling Rett syndrome. In the elder patient, analysis of urinary organic acids disclosed a very high excretion of 5-oxoproline (4.2 to 8.1 mol/mol creatinine) and enzyme assays of leucocyte extracts revealed a profound deficiency of 5-oxoprolinase. However, normal urinary organic acid profiles were found in the younger child. In view of their distinct dysmorphic features and severe growth deficiency, these siblings cannot be considered as Rett Syndrome variants. The Dubowitz and carbohydrate-deficient glycoprotein syndromes were also excluded clinically and biochemically respectively. We conclude that these patients suffer from a hitherto undescribed autosomal recessive disorder, unrelated to the 5-oxoprolinase deficiency of the elder sib.
Conclusion:
The present findings give evidence that 5-oxoprolinase deficiency is not associated with a distinct morbid phenotype.