Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation

Challenges in diagnosis and management of neonatal hyperparathyroidism in a resource-limited country: a case series from a Sudanese family

“…Inactivating mutations in CaSR may affect a single allele (heterozygosis), resulting in the phenotype characteristic of FBHH, or both alleles (homozygosis or compound heterozygosis if no consanguinity exists), leading to NHPT, so that the degree of gene defect is responsible for the great difference in the phenotypic presentation [ 2 , 3 ]. In this report, two siblings had NHPT with homozygous mutations and variability in the degree of severity of symptoms In case 1 {(1V/12), ( Figure 1 )} the symptoms were severe in the face of high, but not too high PTH and extremely high calcium levels, while her younger sibling, case 2 {(1V/13), ( Figure 1 )} presented with milder symptoms, high calcium levels and extremely high levels of PTH.…”

“…Loss of functional mutations results in hypercalcemia with hypocalciuria. There are two forms, a heterozygous mutation resulting in a benign asymptomatic form not requiring treatment, called familial benign hypocalciuric hypercalcemia (FBHH) (OMIM #145980) typically characterized by moderate elevations of serum calcium concentration, inappropriately low urinary calcium excretion, and high normal or mildly elevated parathyroid hormone (PTH) levels [ 2 - 5 ]. The other being a homozygous mutation resulting in a more rare but severe form called neonatal hyperparathyroidism (NHPT) (OMIM # 239200) requiring urgent treatment.…”

“…The latter NHPT presents in the first 6 months of life with severe manifestations of hypercalcemia in the form of respiratory, skeletal, and psychomotor symptoms. PTH levels are high, and if left untreated the condition may be lethal [ 2 - 5 ]. We here report, and for the first time from Sudan, three siblings with this rare condition and discuss the problems that we faced in diagnosing and managing this disorder in a resource-limited country.…”