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A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course.

Çamtosun E, Flanagan SE, Ellard S, Şıklar Z, Hussain K, Kocaay P, Berberoğlu M - J Clin Res Pediatr Endocrinol (2015)

Bottom Line: Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods.The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically.We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

View Article: PubMed Central - PubMed

Affiliation: Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey Phone: +90 312 595 66 35 E-mail: zeynepsklr@gmail.com.

ABSTRACT
Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods. The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically. We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

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Related in: MedlinePlus

Electropherogram showing the homozygous c.636+471G>T cryptic splicing mutation in intron 5 of the HADH gene (lower panel). A sequence trace for a control (upper panel).
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f1: Electropherogram showing the homozygous c.636+471G>T cryptic splicing mutation in intron 5 of the HADH gene (lower panel). A sequence trace for a control (upper panel).

Mentions: Cranial MRI and an electroencephalogram did not reveal any pathology. Normoglycemia was maintained with diazoxide 3 mg/kg/day. Genetic studies by Sanger sequencing did not reveal any mutations in the ABCC8, KCNJ11 or GLUD1 genes, however, sequencing of HADH identified a previously reported homozygous splicing mutation within intron 5 (c.636+471G>T) (Figure 1) (10). The parents who are not known to be consanguineous were both heterozygous for the mutation. The patient is currently 20 years of age and in good health. Mental status and neurological examination were normal at her last follow-up visit. She was reported to have maintained her academic performance at the higher education institution she was attending. Her blood glucose levels continued to be at normal levels with the low dose (2-3 mg/kg/day) of diazoxide she has been receiving. She has reached her final height which is within normal ranges and has a BMI of 24.8 kg/m2.


A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course.

Çamtosun E, Flanagan SE, Ellard S, Şıklar Z, Hussain K, Kocaay P, Berberoğlu M - J Clin Res Pediatr Endocrinol (2015)

Electropherogram showing the homozygous c.636+471G>T cryptic splicing mutation in intron 5 of the HADH gene (lower panel). A sequence trace for a control (upper panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563187&req=5

f1: Electropherogram showing the homozygous c.636+471G>T cryptic splicing mutation in intron 5 of the HADH gene (lower panel). A sequence trace for a control (upper panel).
Mentions: Cranial MRI and an electroencephalogram did not reveal any pathology. Normoglycemia was maintained with diazoxide 3 mg/kg/day. Genetic studies by Sanger sequencing did not reveal any mutations in the ABCC8, KCNJ11 or GLUD1 genes, however, sequencing of HADH identified a previously reported homozygous splicing mutation within intron 5 (c.636+471G>T) (Figure 1) (10). The parents who are not known to be consanguineous were both heterozygous for the mutation. The patient is currently 20 years of age and in good health. Mental status and neurological examination were normal at her last follow-up visit. She was reported to have maintained her academic performance at the higher education institution she was attending. Her blood glucose levels continued to be at normal levels with the low dose (2-3 mg/kg/day) of diazoxide she has been receiving. She has reached her final height which is within normal ranges and has a BMI of 24.8 kg/m2.

Bottom Line: Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods.The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically.We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

View Article: PubMed Central - PubMed

Affiliation: Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey Phone: +90 312 595 66 35 E-mail: zeynepsklr@gmail.com.

ABSTRACT
Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods. The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically. We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

Show MeSH
Related in: MedlinePlus