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Medium chain acyl-CoA dehydrogenase deficiency (MCADD; McKusick 201450) typically presents in the first two years of life with recurrent episodes of hypoketotic hypoglycaemia, lethargy, coma, or sudden infant death. The trigger may be fasting, intercurrent infections, anaesthesia, or surgery. Incidence in the UK is estimated at 0.45–1/10 000 live births.1 We describe the case of a child who presented with marked encephalopathy unexplained by perforated duodenal ulcer, which led to the diagnosis of MCADD.
A 2 year old girl presented with a three week history of coryzal symptoms and three day history of frequent coffee ground vomiting. She was shocked, and had hepatomegaly and decreased conscious level. Blood glucose was 3.9 mmol/l (reference interval 3.3–5.5), plasma sodium 129 mmol/l (135–147), potassium 5.2 mmol/l (3.5–5.0), urea 17.8 mmol/l (3.3–6.6), creatinine 36 mmol/l (30–74), bicarbonate 15 mmol/l (21–28), base excess −5.4 mmol/l (−4 to +2) and C reactive protein 4 mg/l (0–5). Liver function tests and clotting were normal. She was resuscitated with a total of 50 ml/kg of colloid and crystalloid. The following day she relapsed with abdominal distension, shock, and deteriorating conscious level. Investigations showed glucose 14.2 mmol/l, amylase 20 IU/l (8–85), AST 186 IU/l (10–45), and ALT 129 IU/l (10–40). An x ray examination of the abdomen showed free air under the right hemidiaphragm. Emergency laparotomy revealed a single, 1 cm × 1 cm acute perforation in the second part of the duodenum. Histology and rapid urease test (CLO) of the duodenal biopsy for Helicobacter pylori were negative. Fasting blood gastrin was 20 mU/l (10–100). She was discharged home taking omeprazole. Upper gastrointestinal endoscopic biopsy (eight weeks later) for histopathology and CLO test from oesophagus, stomach, antrum, and duodenum were normal.
Analysis of urinary organic acids by gas chromatography and mass spectrometry, obtained a day after clinical presentation, revealed a marked increase in 5-hydroxyhexanoic acid (21% of total organic acids); a modest dicarboxylicaciduria (suberic accounted for 8% and adipic 6% of total organic acids); and a small but significant quantity of hexanoyl glycine (2% total organic acids) in the absence of ketonuria.
Blood obtained a week after clinical presentation, when analysed by tandem mass spectrometry, showed octanoylcarnitine 2.91 μmol/l (≤0.19), hexanoylcarnitine 0.67 μmol/l (≤0.29), and decenoylcarnitine 0.63 μmol/l (≤0.10), with a subnormal concentration of acetylcarnitine 4.0 μmol/l (6.2–27.5). This profile was consistent with MCADD. Polymerase chain reaction/restriction digests based method revealed two mutations in the MCAD gene.
The clinical details coupled with the absence of ketones and the increased 5-hydroxyhexanoic acid led us to look for an abnormality in the oxidation of fatty acids, and resulted in identification of the minor constituent, hexanoylglycine that is recognised as an indicative marker of MCADD. Increases in urinary hexanoylglycine and 5-hydroxyhexanoic acids in the absence of ketonuria have been reported previously in MCAD patients during clinical attack,2 and also in a boy who died.3 Our case was unusual in that the amount of 5-hydroxyhexanoic acid was greater than even the sum of the individual dicarboxylic acids present, although high levels of 5-hydroxyhexanoic acids are reported in acute episodes.4 The increased concentration of octonoyl carnitine in blood was also consistent with a diagnosis of MCADD.
We believe that this is the first report of MCADD presenting with duodenal ulcer. It could be argued that the ulcer was the primary problem and that the decompensation was caused by the subsequent illness. Thus, any child who has unexplained encephalopathy, regardless of its cause and clinical setting, should be screened for MCADD.
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