Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe).

Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C > T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case underlines that the diagnosis of a urea cycle defect should be considered in the differential diagnosis of recurrent idiopathic vomiting in combination with unexplained neurological symptoms also beyond the neonatal period due to the possibility of mild or atypical late-onset presentation (e.g. OTC deficiency in hemizygous males).

Prolonged but successful weaning from left ventricular assist device after cardiac decompensation due to late-recognized coarctation of the aorta in a toddler.

A 2-year-old boy was presented with late-recognized coarctation of the aorta and pulmonary hypertension due to left ventricular failure. The coarctation was corrected at the day of admission with a good postoperative result. However, weaning from the respirator failed despite multiple drug support due to left ventricular failure. Consequently, a left ventricular assist device (LVAD) was implanted 22 days later. The further course was complicated by systemic hypertension and ongoing pulmonary hypertension requiring extensive antihypertensive therapy. The first attempt to wean from LVAD failed and the left ventricle was left completely unloaded for additional 4 weeks. The second weaning attempt, using a very smooth weaning protocol, led to a recovered left ventricle and facilitated the removal of the assist device after a total of 120 days. The patient was discharged with normal cardiac function, but he still requires antihypertensive therapy. We believe that the slow reduction of the LVAD support was the key measure that leads to the successful weaning of the patient, thereby avoiding heart transplantation.

Loss of intrahepatic bile ducts: an important feature of familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, fatal disorder of early infancy. We report two siblings with FHL whose symptoms were dominated by hepatic failure. Both presented with sudden-onset fever and hepatosplenomegaly with progressive abnormalities of clinical biochemistry indices of liver function. One died of hepatorenal failure. The other underwent liver transplantation. Autopsy and explant liver displayed portal and periportal infiltrates of T lymphocytes and histiocytes; an activation of the hepatic mononuclear phagocytic system with focal hemophagocytosis; and almost complete loss of interlobular bile ducts. Paucity of bile ducts dominated in a pre-transplant liver biopsy specimen (and transiently obscured the diagnosis of FHL). Disease recurred in the allograft, again with lymphohistiocytic infiltration and destruction of interlobular bile ducts. Consequently the patient underwent haploidentical peripheral stem cell transplantation. This patient is alive 5 years later. Loss of bile ducts may be an important feature of hepatic involvement by FHL.