Case Reports in Endocrinology

Case Series

Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism

Table 1

Genotypes and pathogenicity prediction by using online prediction tools and the clinical significance according to Varsome.
GeneGenderBirth weight (gr)Symptom onsetBS-INS at diagnosismolecular diagnosisVariantZygosityGnomAD allele frequencyIranome allele frequencyClinical significance (varsome.com)Family historySurgeryResponse to DiazoxideClinical Comments (patients did not response to diazoxide underwent surgery or other drugs)
ABCC8F42004D27–471Mc.331G>AHom^0.000008—Pathogenic—50D—Received diazoxide and octreotide before surgery and sirolimus for 3 months after surgery #
p.Gly111Arg
F26001D34–632.5Mc.2809C>T
p.Leu937=		Hom^——Pathogenic—30D—Received diazoxide and sirolimus after surgery # histologic features: diffused islet hyperplasia
F43503D22–531Mc.1671+1G>AHom^——Pathogenic—57D——
F34003D20–573M,6Dc.2041-21G>AHom^0.00002—Likely Pathogenic+∼—+Received octreotide plus diazoxide in some weeks infancy,continued with diazoxide
M40002D25–331M,4D+∼2M—PET scan: no uptake in pancreas
He died because of sepsis following the surgery
M42001D18–271M+∼∼——Received diazoxide plus octreotide but lost follow up
F31002D28–694Mc.3438dup p.Thr1147HisfsTer48Het (pat)∗——Pathogenic—2M——
F30004D40–125M,22Dc.1109G>C
p.Arg370Thr		Het (de novo)——Uncertain Significance——+—
F28003D25–386Y,9Mc.3438dup
p.Thr1147HisfsTer48		Het (pat)∗——Pathogenic—55D—Received insulin after surgery because of hyperglycemia
F42001D12–281M,2Dc.3151dup
p.Cys1051LeufsTer64		Hom^——Pathogenic———Received diazoxide plus octreotide but lost follow up
M31504D32–541Mc.96C>G
p.Asn32Lys		Comp-Het——Uncertain Significance———Received sirolimus and responded to sirolimus therapy #
c.2041-21G>A0.00002Uncertain Significance
M23005D44–34.63.5Yc.3446G>A
p.Cys1149Ty		Hom^——Likely Pathogenic—3.5Y—Received sirolimus plus diazoxide after surgery
PET scan: avid lesion in the head of pancreas histologic features: islet cell hyperplasia
KCNJ11F38003D28–441M,19Dc.287-288delinsTG
p.Ala96Val		Hom^——Uncertain Significance—2M——
F35002D36–652Mc.370T>A
p.Ser124Thr		Hom^——Uncertain Significance—2M—Received sirulimus ,octreotide and diazoxide before surgery.
Continued with low doses of diazoxide after surgery #
Pet Scan :a mild uptake in the head of pancreas
F41001D28–2822Dc.362T>G
p.Phe121Cys		Hom^——Uncertain Significance+∼∼——Did not responded to diazoxide alone , continued with octreotide and sirolimus #
HADHM310015D38–141Mc.706C>T
p.Arg236Ter		Hom^0.00001—Pathogenic——+PET scan: Uptake in the head of pancreas .Followed by pancreatectomy with no attacks of hypoglycemia
BS: Blood sugar (mg/dl); INS: insulin (IU/ml); D: day; M: Month; Y: year; Pat: paternal; Comp-Het: Compound heterozygote. # The patient previously reported from our center. ^ The mother and father are heterozygote for the variant. ∗ The mother did not have any variant in the three genes and the father was asymptomatic and carrying the variant. ∼ The patients are first cousins. ∼∼ The family had child with similar clinical manifestations but without genetic workups.