Our patient (ID 73387) is a female child, born by an emergency caesarean section at 34 weeks of gestation to consanguineous, first-cousin British Pakistani parents.
Antenatal scans showed that she was small for her gestation, weighing 1.19 kg at birth with a head circumference of 26.7 cm, considerably below the 0.4th centile.
Induction of labour had been attempted because of the growth retardation but had failed, leading to the emergency caesarean section.
The Apgar scores were 4 at 1 min, 7 at 5 min and 9 at 10 min.
She was admitted to the neonatal intensive care unit for continuous positive airway pressure ventilation.
At a few hours of age, she developed a severe lactic acidosis.
The initial lactic acid concentration was 22 mmol/l and subsequently increased to 63 mmol/l (normal range, 0.7–2.1 mmol/l).
She was treated with intravenous infusions of sodium bicarbonate and Tris-hydroxymethyl aminomethane (THAM), but it was never possible to correct the metabolic acidosis.
She also developed hypoglycaemia within hours of birth that was corrected with an intravenous infusion of 15% glucose (7.8 mg/kg/min).
The ammonia concentration was normal.
Urine organic acid profile showed massive excretion of lactic acid and increased phenolic acids, especially hydroxyphenyllactate.
Plasma amino acids showed raised concentrations of alanine and glutamine (1567 and 1369 μmol/l, respectively), consistent with the lactic acidosis; several other amino acids were also mildly increased.
There was gross generalised aminoaciduria.
Blood acylcarnitine analysis was normal.
Echocardiography showed a structurally normal heart and good ventricular function.
Cranial ultrasound showed bilateral intraventricular cysts within the frontal horns and anterior portions of the lateral ventricles.
The left-sided cysts were larger, up to 15 mm in diameter, whereas the largest cyst on the right was 8 mm in diameter.
The choroid plexuses were hyperechoic and irregular, suggesting previous intraventricular haemorrhage.
Abdominal ultrasound showed a distended urinary bladder but was otherwise unremarkable.
There was severe coagulopathy with an extended prothrombin time of 47.7 s (normal 12.3–16.6 s), a very low plasma albumin of 7 g/l (normal 35–50 g/l), otherwise normal liver function tests but a raised creatine kinase of 2700 U/l (normal <300 U/l).
She was transferred to a tertiary centre because of her worsening metabolic acidosis.
She started having seizures at ∼48 h of age.
Despite infusions of bicarbonate and THAM, her acidosis continued to worsen.
Muscle and skin biopsies were performed and the family agreed to the withdrawal of intensive care treatment.
She died aged 55 h.
All documented studies were approved and performed under the ethical guidelines issued by each of our Institutions for clinical studies, with written informed consent obtained from the family.