Ozand et al. (1991) described the deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase 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. One year later, Ozand et al. (1992) found that hereditary deficiency of HMG-CoA lyase comprises up to 16% of inherited metabolic disease (organic acidemia) in Saudi Arabia. They further noted the particularly severe of the disorder among Saudi Arabian patients.
Among nine Saudi HL-deficient probands, Mitchell et al. (1998) found genetic diversity: six were homozygous for the missense mutation arg41 to gln, and two were homozygous for the frameshift mutation F305fs(-2), a deletion of 2 nucleotides in codon 305 resulting in frameshift. Mitchell et al. (1998) used a bacterial expression system for rapid screening of the activity of HL mutant proteins. They pointed out that codons 41 and 42 are important for normal HL catalysis and accounted for a disproportionate 21 (26%) of 82 mutant alleles in their group of HL-deficient probands.
Al-Sayed et al. (2006) studied 72 alleles from 34 Saudi patients that tested positive for 3HMG Aciduria for mutations in the HMCL gene. Clinical data was available for three of these patients. The onset of disease was at 5-months in two patients and 3-days in the other. In addition, six more patients were followed up. All nine patients were on a restricted leucine and fat diet in addition to carnitine at the time of reporting. They were all doing well with normal growth and development. Al-Sayed et al. (2006) observed good neurodevelopmental outcomes in most of the patients, as long as they received appropriate medical attention during episodes of crisis, especially in the first few years of life. The study identified three pathogenic mutations in the 34 patients, one of which was novel.
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