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3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency in Saudi Arabia
P T Ozand1, A al Aqeel, G Gascon
1Department of Paediatrics, King Faisal Specialist Hospital Research Centre, Riyadh, Saudi Arabia.
Insights
3-hydroxy-3-methylglutaryl-CoA lyase deficiency is a serious metabolic disorder in infants. Early diagnosis and treatment are crucial for normal development, though brain abnormalities may persist.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency is an inherited metabolic disorder.
- This study investigates the clinical and diagnostic features in Saudi infants.
Observation:
- 11 Saudi infants diagnosed with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
- Diagnosis confirmed via enzyme activity assays and urinary organic acid analysis.
- Acidotic attacks presented with lethargy, hyperpnea, tachypnea, and seizures, often in the first days of life.
Findings:
- Seven infants experienced severe acidotic attacks within the first day of life.
- Two infants had crises by the third day; two others presented later in infancy.
- Recurrent acidotic attacks occurred following illness or feeding refusal.
- Rapidly progressing acidosis can lead to cardiopulmonary arrest and death if untreated.
Implications:
- Prompt diagnosis and treatment are vital for survival and normal development.
- Despite early intervention, surviving infants may exhibit white matter lesions and mild cerebral atrophy on brain imaging.
- Understanding the presentation and outcomes is crucial for clinical management and genetic counseling.
Abstract:
Deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase has been studied in 11 Saudi infants. The diagnosis was established by the measurement of enzyme activity in lymphocytes, in fibroblasts and, in seven patients, by the gas chromatography/mass spectrometer pattern of excreted organic acids in the urine. In seven infants the disease caused a devastating acidotic attack within the first day of life, while in two the crisis occurred by the third day of life. In two infants from one family the disease appeared later in infancy. The clinical presentation of an acidotic attack is lethargy, hyperpnoea, tachypnoea and seizures, either at birth (two infants), following first feeding (in five infants), or following vomiting or refusal of food in later infancy. The acidotic attacks recurred later in life following minor illness or refusal to eat. The acidosis of this enzyme deficiency progresses rapidly, leading to cardiopulmonary arrest and death within hours of onset unless treated promptly. In four surviving infants diagnosed and treated early, development is normal. Magnetic resonance and computerized tomography brain scans in these infants, however, show white matter lesions and mild atrophy.