Documenting family history in children with hypercholesterolaemia: A lost opportunity.

AIM: To determine whether information about a family history of hypercholesterolaemia or early cardiovascular disease was documented by paediatricians in children and adolescents with elevated low-density lipoprotein (LDL)-cholesterol levels. METHODS: Retrospective chart review of all children with a LDL-cholesterol level ≥95th percentile (3.4 mmol/L) and ≥99th percentile (3.8 mmol/L) at a tertiary paediatric hospital in 2014. RESULTS: Of 86 children with a LDL-cholesterol level ≥3.4 mmol/L, only 18 (20.9%) had documentation of a family history of hypercholesterolaemia or early cardiovascular disease. In those 18, 13 (72.2%) had a family history of hypercholesterolaemia and 11 (61.1%) a family history of early cardiovascular disease. Increasing the LDL-cholesterol cut-off level to ≥3.8 mmol/L (n = 46) did not improve documentation of a family history (9/46, 19.6%). CONCLUSIONS: In patients with elevated LDL-cholesterol levels, paediatricians rarely document a positive or negative family history of hypercholesterolaemia or early cardiovascular disease. This represents a lost opportunity to diagnose children and adolescents with familial hypercholesterolaemia.

Factors influencing neonatal thyroid-stimulating hormone concentrations as a measure of population iodine status.

BACKGROUND: The World Health Organization (WHO) has recommended measurement of neonatal thyroid-stimulating hormone (TSH) as a marker of population iodine status. A population is considered iodine sufficient when <3% of neonatal blood samples collected 3-4 days after birth have TSH concentrations >5 mIU/L. However, changes in technology and clinical practices have opened the WHO criteria to various interpretations. AIM: This study aimed to investigate the effects of time of sampling, weight, and sex on neonatal TSH concentrations by analyzing neonatal TSH data, based on the WHO criteria for population iodine sufficiency. METHODS: We analyzed the Western Australian (WA) Newborn Screening Program records for 198,826 babies born in WA between 2005 and 2011, to determine the relationship between neonatal TSH concentrations and time of sampling, weight, and sex. RESULTS: The proportion of TSH results above the WHO cut-off was higher for samples collected 48-72 h after birth rather than later, for males, for birth weights below 2500 g, and when a cut-off of 5.0 mIU/L was used. CONCLUSION: Following changes in newborn screening protocols and earlier collection of blood samples, the WHO criteria appear inappropriate. We recommend that WHO revise current guidelines regarding use of neonatal TSH for monitoring population iodine status.

Ethnic and gender differences in rates of congenital adrenal hyperplasia in Western Australia over a 21 year period.

AIM: To evaluate the incidence, sex distribution, ethnicity, age at diagnosis, clinical presentation and morbidity of all childhood-onset congenital adrenal hyperplasia (CAH) cases in Western Australia (WA) between 1990 and 2010, a state where newborn screening for CAH is not in place. METHODS: The total number of all known CAH cases was identified. Case files were reviewed retrospectively to determine clinical details. Classical CAH (C-CAH) was defined as patients presenting before 6 months of age and non-classical (NC-CAH) as presenting after 6 months. RESULTS: Of the 41 CAH cases (26 female) born in WA, 5(12.2%) were of Aboriginal ethnicity. CAH was due to 21-hydroxylase deficiency in 40 cases. Of those with 21-hydroxylase deficiency, 37 were C-CAH (25 female) and 3 NC-CAH (all male). The incidence of C-CAH in WA was estimated to be 0.67 per 10, 000 live births (1:14, 869). The incidence rate ratio of Aboriginal compared with non-Aboriginal C-CAH was 2.45 (95% confidence interval 0.96-6.29). The mean age of diagnosis of C-CAH cases was lower in females (8.9 ± 2.5 days) compared to males (23.4 ± 9.8 days). Among these males, 72.7% presented initially with adrenal crisis. CONCLUSION: The estimated incidence of classical CAH is similar to composite worldwide data. The increased female-to-male ratio is not in keeping with the expected sex distribution seen in a recessively inherited disease. The delayed diagnosis in males, with a significant proportion presenting with adrenal crisis, could be avoided with newborn screening. The higher rate of CAH in patients with Aboriginal ethnicity is a novel observation.

Structural chromosome disruption of the NR3C2 gene causing pseudohypoaldosteronism type 1 presenting in infancy.

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance presenting in infancy with renal salt wasting and failure to thrive. Here, we present the case of a 6-week-old baby girl who presented with mild hyponatraemia and dehydration with a background of severe failure to thrive. At presentation, urinary sodium was not measurably increased, but plasma aldosterone and renin were increased, and continued to rise during the subsequent week. Despite high calorie feeds the infant weight gain and hyponatraemia did not improve until salt supplements were commenced. Subsequently, the karyotype was reported as 46,XX,inv (4)(q31.2q35). A search of the OMIM database for related genes at or near the inversion breakpoints, showed that the mineralocorticoid receptor gene (NR3C2) at 4q31.23 was a likely candidate. Further FISH analysis showed findings consistent with disruption of the NR3C2 gene by the proximal breakpoint (4q31.23) of the inversion. There was no evidence of deletion or duplication at or near the breakpoint. This is the first report of a structural chromosome disruption of the NR3C2 gene giving rise to the classical clinical manifestations of pseudohypoaldosteronism type 1 in an infant.

Late-onset carbamoyl phosphate synthetase 1 deficiency in an adult cured by liver transplantation.

Urea cycle disorders (UCDs) are rare causes of hyperammonemic encephalopathy in adults. Most UCDs present in childhood and, if unrecognized, are rapidly fatal. Affected individuals who survive to adulthood may remain undiagnosed because of clinicians' unawareness of the condition or atypical presentations. We describe the case of a 49-year-old man who initially presented with a stroke and developed hyperammonemic encephalopathy over a period of 8 months. A diagnosis of carbamoyl phosphate synthetase type 1 deficiency was made, and the patient was referred for liver transplantation. One year after liver transplantation, the patient had normal plasma ammonia concentrations and had returned to work.