#229700
ICD+
| ||||||||||||||||||||||||||||||||||||||||||
| FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY | ||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||
| Clinical Synopsis | ||||||||||||||||||||||||||||||||||||||||||
| TEXT | ||||||||||||||||||||||||||||||||||||||||||
| A number sign (#) is used with this entry because fructose-1,6-bisphosphatase deficiency is caused by mutation in the gene encoding fructose-1,6-bisphosphatase-1 (FBP1; 611570). | ||||||||||||||||||||||||||||||||||||||||||
| Description | ||||||||||||||||||||||||||||||||||||||||||
| Fructose-1,6-bisphosphatase deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis. Patients present with hypoglycemia and metabolic acidosis on fasting and may have episodes of hyperventilation, apnea, hypoglycemia, and ketosis. Although the disorder may be lethal in the newborn period, proper treatment yields an excellent prognosis (Kikawa et al., 1997; Matsuura et al., 2002). | ||||||||||||||||||||||||||||||||||||||||||
| Clinical Features | ||||||||||||||||||||||||||||||||||||||||||
| Baker and Winegrad (1970) described a girl with hypoglycemia and metabolic acidosis on fasting. Biochemical studies showed impaired gluconeogenesis due to deficiency of hepatic fructose-1,6-diphosphatase. A sib had died of a clinically similar ailment. The patient of Baerlocher et al. (1971) had consanguineous parents and 2 sisters had died, apparently of the same disorder. Hulsmann and Fernandez (1971) reported a consanguineous family with 2 affected sibs. Pagliara et al. (1972) reported an 8-month-old female who experienced attacks of hyperventilation when weaned to baby food at age 6 months. She was admitted with severe lactic acidosis and hypoglycemia. Adequate carbohydrate intake, with sucrose and fructose excluded, prevented lactic acidosis and hypoglycemia. No hepatic fructose-1,6-diphosphatase activity was detected. Greene et al. (1972) reported successful treatment of 2 patients with folic acid. Odievre et al. (1975) observed 2 affected sisters. Buhrdel et al. (1990) reported 4 unrelated infants, 3 boys and a girl, with fructose-1,6-diphosphatase deficiency. All 4 patients had less than 25% residual hepatic enzyme activity. Of 3 patients analyzed, 2 boys showed the enzyme deficiency in leukocytes, whereas the girl had normal leukocyte enzyme activity. Three patients had pronounced neonatal hyperbilirubinemia requiring exchange transfusion. Moses et al. (1991) reported 9 patients belonging to 6 families in Israel; 2 of the families were Jewish, 3 Moslem Arabs, and 1 Druze. All patients had neonatal hypoglycemia, lactic acidosis, and an abnormal fructose or glycerol loading test. At a later age, instances of hypoglycemia occurred in patients with or without preceding illness. Hypoglycemic attacks were associated with severe hyperuricemia and metabolic acidosis. Therapeutic measures included a restriction in fructose intake and avoidance of prolonged fasting, particularly during febrile episodes. Kikawa et al. (1997) reported 13 Japanese patients from 11 families with FBP1 deficiency. Three families were consanguineous. All patients had recurrent attacks of metabolic acidosis and hypoglycemia associated with vomiting, drowsiness, or tachypnea. Age at onset of the first symptoms ranged from day 1 to 4 years. Matsuura et al. (2002) reported a Japanese girl with FBP1 deficiency. She presented at age 2 months with a febrile illness and hyperventilation. Laboratory studies showed hypoglycemia and severe metabolic acidosis. No FBP1 activity was detected in leukocytes; her parents had normal leukocyte enzyme activity. A high carbohydrate diet and reduction of fructose intake completely prevented further episodes. Molecular analysis identified compound heterozygous mutations in the FBP1 gene (611570.0005; 611570.0006). | ||||||||||||||||||||||||||||||||||||||||||
| Diagnosis | ||||||||||||||||||||||||||||||||||||||||||
| Buhrdel et al. (1990) and Besley et al. (1994) described female patients with FBP1 deficiency and normal enzyme activity in leukocytes. Kikawa et al. (1997) noted that enzyme assay using leukocytes is not reliable for detection of FBPase deficiency. | ||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||||||||
| In 10 of 13 Japanese patients with FBP1 deficiency, Kikawa et al. (1997) identified homozygous or compound heterozygous mutations in the FBP1 gene. Total RNA was isolated from cultured monocytes. A 1-bp insertion (960insG; 611570.0001) was the most common mutation, present in 12 of 20 alleles. | ||||||||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||||||||
| El-Maghrabi et al. (1995); Kikawa et al. (1995); Melancon and Nadler (1972) | ||||||||||||||||||||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||