ABCMdb

ABCC8 p.Arg1393Leu

Predicted by SNAP2:	A: D (91%), C: D (85%), D: D (95%), E: D (95%), F: D (95%), G: D (91%), H: D (91%), I: D (91%), K: D (91%), L: D (91%), M: D (91%), N: D (71%), P: D (95%), Q: D (85%), S: D (85%), T: D (91%), V: D (91%), W: D (95%), Y: D (91%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D,

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[hide] A novel case of compound heterozygous congenital h... Int J Pediatr Endocrinol. 2015;2015(1):16. doi: 10.1186/s13633-015-0012-4. Epub 2015 Jul 15. Brady C, Palladino AA, Gutmark-Little I
A novel case of compound heterozygous congenital hyperinsulinism without high insulin levels.
Int J Pediatr Endocrinol. 2015;2015(1):16. doi: 10.1186/s13633-015-0012-4. Epub 2015 Jul 15., [PMID:26180531]

Abstract [show]
BACKGROUND: Congenital hyperinsulinism leads to unregulated insulin secretion and hypoglycemia. Diagnosis can be difficult and genetic testing may be warranted. CASE: This patient initially presented at 11 months with seizure activity secondary to severe hypoglycemia. Her diagnostic evaluation included genetic studies, which confirmed congenital hyperinsulinism. A novel combination of mutations in the ABCC8 gene leading to diffuse, diazoxide-unresponsive congenital hyperinsulinism was identified. Mutation analysis of ABCC8 showed three variants (R1215W - paternal, pathogenic; W739C - maternal, variant of unknown significance; R1393L - maternal, variant of unknown significance). Her clinical course continues to be complicated by severe, refractory hypoglycemia at age 3 years. CONCLUSION: We describe a novel compound heterozygous mutation leading to diffuse, diazoxide-unresponsive congenital hyperinsulinism. This case illustrates challenges associated with diagnosing and managing congenital hyperinsulinism and the importance of genetic testing.

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No. Sentence Comment
5 Mutation analysis of ABCC8 showed three variants (R1215W - paternal, pathogenic; W739C - maternal, variant of unknown significance; R1393L - maternal, variant of unknown significance). Login to comment
59 The R1215W variant was found to be paternally-inherited while the W739C and R1393L variants were maternally inherited. Login to comment
62 In our patient, the significance of the maternal variants was unclear as they had not been previously described in Table 1 Fasting challenge results Test name (Normal range) Laboratory result IGFBP-1 (ng/mL) (5-9 years: 15-95; no reference range for patients <5 years) 61 Insulin (<2-13 bc;IU/mL fasting) 0.2 Glucose (>70 mg/dL/3.885 mmol/L) 32/1.776 C-peptide (0.8-3.5 ng/mL) 0.5 BOHB (0-3.0 mg/dL) 4.3 (0.41 mmol/L) Free Fatty Acids (0.5-0.9 mmol/L) 0.46 Growth Hormone (>7 ng/mL) 3 Table 2 Genetic results (ABCC8 Mutation) Mutation Inheritance Interpretation c. R1215W Paternal Pathogenic c. W739C Maternal VUS c. R1393L Maternal VUS VUS variant of unknown significance CHI cases. Login to comment
115 We suspect the R1393L variant is pathogenic and could act either recessively or dominantly. Login to comment