Congenital Brucellosis: A Systematic Review of the Literature.

BACKGROUND: Knowledge of the spectrum of presentations and the outcome of congenital brucellosis should expedite diagnosis and improve prognostication. METHODS: A systematic review of literature of cases of congenital brucellosis was performed on October 10, 2017 (registered as PROSPERO CRD42017072061). RESULTS: A case seen by the authors was added to the review, yielding 44 reported cases of which 22 (50%) were from Turkey, Saudi Arabia, or Kuwait. For cases with the gestational age reported, 23 of 37 (62%) were preterm. The species was Brucella melitensis in 35 cases, Brucella abortus in 3 cases and not documented in 6 cases. The diagnosis was based on a positive blood culture from the first day of life in 20 cases (45%). Presentation was usually typical for a bacteremic infant of that GA, but two infants were asymptomatic at diagnosis. There were two recurrences and seven deaths (six in preterm infants), but the role of Brucella infection in the deaths was not clear. CONCLUSION: Brucellosis remains a concern in endemic countries, adversely affecting pregnancy and very rarely causing neonatal infection. Prematurity appeared to be the prime cause of death in neonates with congenital brucellosis.

Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family.

Hyperinsulinaemic hypoglycaemia (HH) is caused by mutations in the key genes involved in regulation of insulin secretion from the pancreatic ß-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.