Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family.
PMID 25915078 | DOI 10.1515/jpem-2015-0033 · Journal of pediatric endocrinology & metabolism : JPEM · 2015 · View on PubMed ↗
Hyperinsulinaemic hypoglycaemia (HH) is caused by mutations in the key genes involved in regulation of insulin secretion from the pancreatic β-cells and mutations in ABCC8 and KCNJ11 are the most common causes of HH. Mutations in HADH (which encodes the enzyme 3-hydroxyacyl-CoA dehydrogenase) are a rare cause of HH. We report three siblings (21, 9, and 7 years old) from a consanguineous Saudi family with HH due to a homozygous mutation in HADH. All three siblings presented with HH in the 1st year of life. HH responded well to medical therapy (diazoxide/octreotide) although the 1st sibling suffered neurological damage. The protein load test revealed protein sensitivity in the 21-year-old proband, the oldest reported patient with HH secondary to a HADH mutation. Genetic analysis revealed a homozygous HADH splicing mutation (c.133-1G>A) in all three siblings. HADH mutations can present in later infancy or childhood with severe HH that is usually diazoxide responsive. Severe neurological complications such as epilepsy and developmental delay can be associated with HADH mutations. This is the 1st report of HH due to HADH mutation in an adult suggesting that HH could persist into adulthood possibly becoming milder over the years.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | HADH | “Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family.” | 0.98 | hgnc_dict_v1 |
| gene | ABCC8 | “Hyperinsulinaemic hypoglycaemia (HH) is caused by mutations in the key genes involved in regulation of insulin secretion from the pancreatic β-cells and mutations in ABCC8 and KCNJ11 are the most common causes of HH.” | 0.98 | hgnc_dict_v1 |
| gene | KCNJ11 | “Hyperinsulinaemic hypoglycaemia (HH) is caused by mutations in the key genes involved in regulation of insulin secretion from the pancreatic β-cells and mutations in ABCC8 and KCNJ11 are the most common causes of HH.” | 0.98 | hgnc_dict_v1 |
| phenotype | developmental delay | “Severe neurological complications such as epilepsy and developmental delay can be associated with HADH mutations.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | epilepsy | “Severe neurological complications such as epilepsy and developmental delay can be associated with HADH mutations.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family. We report three siblings (21, 9, and 7 years old) from a consanguineous Saudi family with HH due to a homozygous mutation in HADH.” | 0.95 | saudi_context_rules_v1 |
| variant | c.133-1G>A | “Genetic analysis revealed a homozygous HADH splicing mutation (c.133-1G>A) in all three siblings.” | 0.95 | hgvs_regex_v1 |