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Carrier detection of pyruvate carboxylase deficiency in fibroblasts and lymphocytes
Insights
Pyruvate carboxylase deficiency is an autosomal recessive disorder. Lymphocyte and fibroblast tests can identify carriers of this condition.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Pyruvate carboxylase (PC) deficiency is a rare metabolic disorder affecting multiple organs.
- The PC Portland deficiency variant presents with severe symptoms.
- Understanding the inheritance pattern is crucial for genetic counseling and carrier detection.
Purpose of the Study:
- To determine the activity of pyruvate carboxylase in family members of a patient with PC deficiency.
- To investigate the potential of using lymphocytes and fibroblasts for carrier detection.
- To explore the effect of fasting on enzyme activity in lymphocytes.
Main Methods:
- Enzyme activity assays for pyruvate carboxylase (E.C. 6.4.1.1) were performed.
- Samples were obtained from circulating peripheral lymphocytes and cultured skin fibroblasts.
- Activity levels were compared to the lowest normal range.
Main Results:
- Lymphocyte pyruvate carboxylase activity varied among family members: mother (33-39%), father (11-29%), brother (82-103%), and sister (38-48%).
- Fibroblast activity was reduced in the parents: mother (42%), father (34%).
- Fasting did not increase pyruvate carboxylase or mitochondrial PEPCK activity in lymphocytes.
Conclusions:
- The study confirms an autosomal recessive inheritance pattern for pyruvate carboxylase deficiency.
- Lymphocytes and fibroblasts are suitable biomarkers for detecting carriers of PC deficiency.
- Enzyme activity levels in lymphocytes are not significantly altered by short-term fasting.
Abstract:
Pyruvate carboxylase (E.C. 6.4.1.1) activity was determined in the circulating peripheral lymphocytes and cultured skin fibroblasts from the family of a patient with hepatic, cerebral, renal cortical, leukocyte, and fibroblast pyruvate carboxylase deficiency (PC Portland deficiency). Lymphocyte activities were: mother, 33--39%; father, 11--29%; brother, 82--103%; and sister, 38--48% of the lowest normal. Fibroblasts from the patient's mother and father had 42 and 34%, respectively, of the activity of the lowest normal. These data demonstrate that the disease is inherited in an autosomal recessive manner and that lymphocytes and fibroblasts can be used to detect carriers. Neither pyruvate carboxylase nor mitochondrial PEPCK activity in lymphocytes was increased by a 21-hr fast.