Background The aim of this study was to describe the incidence and spectrum of early clinical presentations of congenital adrenal hyperplasia (CAH) in an unscreened population. Methods A national retrospective observational study was undertaken to identify all children diagnosed with CAH in the Republic of Ireland, between January 2005 and December 2019. Reporting clinicians completed anonymized clinical questionnaires. Results There were 103 cases of CAH reported and 69 cases met the study inclusion criteria. The estimated annualized incidence of CAH in the Republic of Ireland was 1:14,754 or 0.07 cases per 1,000 live births. Forty-seven children presented clinically in the first six months of life, but only 17 of these had a confirmed diagnosis by day 10. Of these early presentations, there were 28 infants with salt-wasting, 15 females presented with virilized genitalia and four infants were detected due to a family history of CAH. Female infants presented at a median age of 0 days [IQR 0–1] and males at 14 days [IQR 9–21]. Seventy-eight percent of salt-wasting presentations occurred after day 10. Delays in clinical presentation, biochemical diagnosis and treatment initiation were identified. Conclusions The incidence of CAH is higher in Ireland than in other unscreened populations. In the absence of screening, clinicians should be aware of the possibility of CAH and appropriate investigations should be urgently requested. Life-threatening salt-wasting is the most frequent clinical presentation and many cases could be detected prior to decompensation if newborn screening were introduced.

Mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG Co‐A) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis which has traditionally been associated with hypoketotic hypoglycemia, hepatomegaly and encephalopathy, presenting in early childhood following a period of fasting. We report the third case of mHS deficiency presenting in the absence of hypoglycemia, with profound biochemical abnormalities and further evidence of potential specific diagnostic biomarkers. A previously well, 20‐month old, unvaccinated male, of nonconsanguineous Polish heritage, presented with encephalopathy, hepatomegaly, severe metabolic acidosis, and mild hyperammonemia following a brief intercurrent illness. The patient was reported to have taken colloidal silver prior to presentation, posing a further diagnostic challenge. Additionally, he developed features suggestive of hemophagocytic lymphohistiocytosis during treatment. While the patient was normoglycemic prior to dextrose administration, the sample was markedly lipemic, with significant hypertriglyceridemia detected. Urine organic acid analysis revealed dicarboxylic aciduria with 4‐hydroxy‐6‐methyl‐2‐pyrone (4HMP) and the presence of three other previously reported putative biomarkers for mHS deficiency. Glutarate was markedly elevated in the initial chromatogram, with a mild increase in 3‐hydroxyglutarate (3HG) persisting. Raised acetylcarnitine was detected on acylcarnitine profile. Molecular genetic analysis of the HMGCS2 gene identified compound heterozygosity for known pathogenic mutations c.634G>A and c.1016+1G>A, confirming the diagnosis of mHS deficiency. This case provides further evidence that hypoglycemia is not invariably present in symptomatic mHS deficiency. We propose that elevated acetylcarnitine, triglycerides, and 3HG are additional biochemical features during acute presentations. With the expansion of novel biomarkers, further cases of this rare disorder may emerge.

Symptomatic HIV infection was first diagnosed in an Irish child in 1985. A prospective study was initiated to determine the vertical transmission rate (VTR) of HIV and the average age of infant seroreversion and to monitor clinical, immunologic and virologic evidence for HIV infection in seroreverters. Ninety three HIV positive infants have been prospectively identified since 1985. The predominant underlying maternal risk factor for HIV infection is intravenous drug use (IVDU) (96 per cent). Of 93 infants, median gestational age was 40 weeks and median birth weight 3125 grams. Ninety-four per cent of infants were bottle fed. Currently 72 (77 per cent) infants are uninfected, 12 (13 per cent) are infected, 4 (4.5 per cent) are indeterminate and 5 (5.5 per cent) have been lost to follow up. The intermediate estimate of vertical transmission rate (VTR) is 14.3 per cent. The median age at documented seroreversion was 12 months. There are no significant differences between infected and non-infected children in male/female ratio, gestational age, mode of delivery or birth weight. Strategies to reduce the transmission of HIV among drug users in combination with routine antenatal screening and antiretroviral prophylaxis of vertical transmission are all measures which can reduce HIV infection in our children.