Deficiency of glycerol kinase (EC 2.7.1.30).

Abstract

We describe the case of a 10-year-old boy who had been admitted on several occasions with a diagnosis of gastroenteritis. He had been severely ill, and on one occasion lost consciousness. He had a metabolic acidosis on these occasions. Examination of the urine by gas chromatography-mass spectrometry showed a large peak, identified as glycerol. The concentration of glycerol in the urine was 40-280 mmol/L and the concentration in plasma about 2 mmol/L. He was subjected to a fast of 21 h, at the end of which he expressed feelings of discomfort and nausea, began vomiting, and became somnolent. During this period the blood glucose concentration was only slightly decreased, the plasma glycerol concentration increased to 4.9 mmol/L, and the plasma lactate concentration increased to 3.8 mmol/L. During work on a bicycle ergometer for 35 min (40 W) he complained of muscle pain and became nauseated, but there was no significant increase in the concentration of plasma glycerol. The activity of glycerol kinase (EC 2.7.1.30) in leukocytes and cultured fibroblasts was less than 1% of the value for healthy subjects.

Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis

“…Her 11-y-old daughter was a carrier of the mutation and, according to the mother, she has always been sensitive to a short period of food deprivation. Results from the first fasting test in case 1, carried out when the boy was 10 y old, have been presented earlier (4). In brief, he was able to maintain a normal blood glucose concentration (4.2 mmol l À1 ) throughout the fast, but the concentrations of 3-hydroxybutyrate (5.9 mmol l À1 ) and acetoacetate (1.3 mmol l À1 ) reached levels two to five times higher than in normal children at the same age who fasted for the same period (8,9).…”

“…The early history has been described previously (4). In brief, when admitted to the hospital at 4 y and 5 mo of age he was pale, somnolent, hyperventilating and complaining of severe abdominal pains.…”

“…They have been without symptoms that can be ascribed to GKD and as far as is known have not had any such symptoms in childhood. In 1983, the authors described a 10-y-old boy with episodes of vomiting, metabolic acidosis and clinical symptoms of hypoglycaemia, who sometimes lost consciousness in conjunction with slight infections or after even moderate physical activity (4). He was the first patient described with severe symptoms due to isolated GKD.…”

Complex glycerol kinase deficiency: A contiguous gene syndrome involving the Duchenne muscular dystrophy, glycerol kinase, and adrenal hypoplasia congenita loci

“…In 1978, a family was described with a 70-year-old proband, whose brother and his daughter's son were incidentally noted to have hyperglycerolemia and GKD but no consistently associated clinical abnormalities [Rose and Haines, 19781. Subsequently, two unrelated boys were reported with episodes of vomiting, acidemia, and somnolence or stupor, occasionally progressing to loss of consciousness, who both had their initial episodes at 4 years of age and exhibited glycerol accumulation and GKD [Eriksson et al, 1983; Ginns et al, 19841. These individuals are representatives of the three forms of GKD, now recognized as the infantile or complex, juvenile, and adult or benign forms of GKD [McCabe, 19951.…”

Asthma as the First Presenting Symptom of Complex Glycerol Kinase Deficiency

“…However, in many cases the full syndrome does not manifest itself until later in life, while congenital adrenal hypoplasia commonly occurs in the neonatal period (1, 4,5). Patients with CGKD are often diagnosed as having "cerebral palsy" or "myopathy" until they present with Addison crisis (6,7). We have had experience with two cases who presented with asthma as the first clinical symptom, which seemed to be a mild form of Addison crisis, and was treated with bronchodilators prior to the exact diagnosis.…”