BackgroundTyrosinemia type 1 (TT1) is an autosomal recessive disorder caused by deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). TT1 usually presents in infancy with features suggestive of liver disease or with sepsis-like symptoms.Case presentationWe report two Saudi siblings with TT1. Case 1 was a male infant who presented at 2 months old with fever, vomiting and refusal of feeding. Examination revealed a sick-looking infant with signs of severe dehydration and hypovolemic shock. He was jaundiced, and had hepatomegaly and elevated liver enzymes. Echocardiography was performed in light of a lack of response to inotropes, and revealed biventricular and interventricular septal hypertrophies. The ventricular ejection fraction was 65%. Urine organic acid analysis showed elevated succinylacetone, consistent with a diagnosis of TT1. An FAH gene study identified a c.1 A > G homozygous mutation. This patient responded well to intensive cardiorespiratory therapy, tyrosine-free formula, and oral 2-nitro-4- trifluoromethylbenzyl 1, 3 cyclohexanedione (NTBC). Echocardiographic findings reverted to normal after 4 weeks. Case 2 was the younger brother of Case 1, and was born 6 months after his brother had been confirmed with tyrosinemia. Pregnancy and delivery were uneventful. Serum amino acid and organic acid analyses 4 days after birth confirmed tyrosinemia. DNA analysis identified a c.1 A > G homozygous mutation, as in his brother. Echocardiography was normal. Special formula and NTBC were commenced on day 7 of life. The infant remained asymptomatic after 9 months of follow-up.ConclusionsThese cases highlight TT1 as a treatable cause of cardiomyopathy in children. It also supports the idea that early diagnosis and treatment may prevent the development of cardiomyopathy associated with tyrosinemia.

We report a Saudi girl who presented at birth with neonatal diabetes, duodenal atresia, and progressive cholestasis. After other gene testing was negative, the clinical diagnosis of Mitchell-Riley syndrome was ultimately considered and further genetic analysis revealed a novel missense homozygous variant in RFX6: c.983A>T (p.asp328Val). Despite intensive management, the patient died from severe Klebsiella pneumoniae sepsis at 5 months of age. This rare syndrome should be suspected in any neonate with hyperglycemia complicated by intestinal atresia and/or progressive cholestasis that could suggest biliary hypoplasia. Early recognition and diagnosis through genetic testing are essential for guiding aggressive clinical management as well as family counseling, particularly in light of the high possibility of early death in this highly complex disorder.