Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ7-sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3β,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5 ng/mL).

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The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

C hildren with inborn errors of metabolism (IEM) or inherited metabolic disorders often present with vague and nonspecific symptoms that pose diagnostic and management challenges. [1][2][3] The initial hours of management are critical as it determines the clinical course and eventual clinical outcome. 4,5 We recently managed a cluster of infants with IEM who presented with vague and nonspecific symptoms. For instance, a toddler presented to a private practitioner with vomiting, fluctuating conscious state, irritability, and poor feeding. Urea cycle disorder was suspected as blood investigations revealed alkalosis, hyperammonemia, lack of ketosis, and acute liver failure. He was stabilized with intravenous sodium benzoate, arginine, carnitine, and continuous venovenous hemodialysis filtration therapy. Fortunately, in this case, the acute liver failure was self-limiting.A multidisciplinary team approach was adopted in the management of this patient. This case, together with many other cases of IEM conditions presenting in infancy, has a number of issues in common, including