Alternative titles; symbols
SNOMEDCT: 62151007; DO: 0112262;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p15.1 | Hypoglycemia of infancy, leucine-sensitive | 240800 | Autosomal dominant | 3 | ABCC8 | 600509 |
A number sign (#) is used with this entry because leucine-sensitive hypoglycemia of infancy (LIH) is caused by heterozygous mutation in the SUR1 gene (ABCC8; 600509).
Leucine-sensitive hypoglycemia (LIH) is a condition in which symptomatic hypoglycemia is provoked by protein meals or the amino acid leucine (summary by Magge et al., 2004).
Cochrane et al. (1956) and DiGeorge and Auerbach (1960) reported familial infantile hypoglycemia precipitated by leucine. The family reported by Cochrane et al. (1956) included a father and 2 daughters who developed hypoglycemia after high protein feedings. Hypoglycemia was also elicited by administration of oral or intravenous infusions of leucine.
Ebbin et al. (1967) observed symptomatic hypoglycemia with leucine sensitivity in a mother and daughter. Other cases of adults with leucine sensitivity have had islet adenomas, which apparently were not present in this case.
Mabry et al. (1960) reported a Caucasian boy (patient J.C.) who presented with hypoglycemic seizures in early infancy and was shown to be susceptible to hypoglycemia when given an intravenous infusion of leucine. His father experienced faintness and dizziness after administration of oral leucine, with a blood sugar level that fell from 100 to 60 mg%; he refused further testing. The proband had 2 brothers who were reported to be healthy. Mabry et al. (1960) also studied an African American girl who had leucine-induced hypoglycemia. Her parents were unavailable for study. In addition, the authors tested another 7 children with hypoglycemia of undetermined etiology, but leucine had no effect on their blood sugar levels.
The transmission pattern of LIH in the family reported by Mabry et al. (1960) and Magge et al. (2004) was consistent with autosomal dominant inheritance.
Magge et al. (2004) examined a nephew of the patient of Mabry et al. (1960) (patient J.C.) who presented with neonatal hyperinsulinism. At 10 months of age the proband had a positive leucine AIR (acute insulin response) test. The proband and 4 other members of his family shared a heterozygous arg1353-to-his mutation in the SUR1 gene (R1353H; 600509.0012). Five of 5 affected family members showed an abnormal positive calcium AIR, and 2 of the 5 showed a positive leucine AIR. Protein-induced hypoglycemia was demonstrated in 5 of 6 affected subjects.
Magge et al. (2004) reported that the proband of the family examined by them had an excellent response to diazoxide therapy, unlike most cases of hyperinsulinism associated with recessive SUR1 mutations.
Cochrane, W. A., Payne, W. W., Simpkiss, M. J., Woolf, L. I. Familial hypoglycemia precipitated by amino acids. J. Clin. Invest. 35: 411-422, 1956. [PubMed: 13306783] [Full Text: https://doi.org/10.1172/JCI103292]
DiGeorge, A. M., Auerbach, V. H. Leucine-induced hypoglycemia: a review and speculations. Am. J. Med. Sci. 240: 792-801, 1960.
Ebbin, A. J., Huntley, C., Tranquada, R. E. Symptomatic leucine sensitivity in a mother and daughter. Metabolism 16: 926-932, 1967.
Mabry, C. C., DiGeorge, A. M., Auerbach, V. H. Leucine-induced hypoglycemia. J. Pediat. 57: 526-538, 1960. [PubMed: 13764666] [Full Text: https://doi.org/10.1016/s0022-3476(60)80080-7]
Magge, S. N., Shyng, S.-L., MacMullen, C., Steinkrauss, L., Ganguly, A., Katz, L. E. L., Stanley, C. A. Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor. J. Clin. Endocr. Metab. 89: 4450-4456, 2004. [PubMed: 15356046] [Full Text: https://doi.org/10.1210/jc.2004-0441]
McQuarrie, I. Idiopathic spontaneously occurring hypoglycemia in infants. Clinical significance of problems and treatment. Am. J. Dis. Child. 87: 399-428, 1954. [PubMed: 13147532]