Hyperprolinemia type I caused by homozygous p.T466M mutation in PRODH

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Hyperprolinemia type I (HPI) is an inherited metabolic disorder.
• It results from defects in the proline oxidase enzyme, encoded by the PRODH gene.
• HPI is typically inherited in an autosomal recessive pattern.

Purpose of the Study:

• To report a clinical case of Hyperprolinemia type I.
• To identify the specific genetic mutation and polymorphisms associated with the patient's HPI.
• To correlate the clinical presentation with the identified genetic findings.

Main Methods:

• Plasma amino acid analysis was performed to detect elevated proline levels.
• Sanger sequencing was used to identify mutations and polymorphisms in the PRODH gene.
• Clinical evaluation included assessment of physical growth and cognitive function.

Main Results:

• The patient was diagnosed with Hyperprolinemia type I.
• A specific mutation, NM_016335.4 (PRODH_v001):c.1397C>T (p.T466M), and PRODH gene polymorphisms were identified.
• Clinical manifestations included short stature, preference for carbohydrate-rich foods, and mild intellectual disability.

Conclusions:

• The identified PRODH gene mutation and polymorphisms are associated with Hyperprolinemia type I in this patient.
• The clinical phenotype, including neurodevelopmental features, aligns with HPI.
• This case highlights the importance of genetic analysis in diagnosing and understanding metabolic disorders.