Hypergalactosemia at newborn screening due to congenital portosystemic shunts: a narrative literature review and case report

Galactosemia is a rare inherited disorder of carbohydrate metabolism that can manifest with severe multi-organ involvement. Diagnosis relies on newborn screening (NBS) followed by confirmatory enzyme and genetic testing. Neonatal hypergalactosemia can rarely be secondary to other conditions including liver vascular anomalies. A narrative literature review on secondary galactosemia at NBS associated with congenital portosystemic shunts (CPSS) was performed. We identified 40 articles reporting 94 cases of neonatal hypergalactosemia associated with different types of CPSS, and in thirteen cases also with hepatic hemangiomas (HH). In 86 patients, galactosemia represented a clue to the diagnosis of the vascular anomaly. Other metabolic alterations included hyperammonemia and elevated biliary acids. Additional congenital anomalies, mainly heart defects, were reported in 27 patients. Shunt complications (encephalopathy, focal nodular hyperplasia, pulmonary hypertension, cardiac failure, and hepatopulmonary syndrome) were described in 25 patients. Abdominal Doppler ultrasound (DUS) represented the first line investigation, variably complemented by magnetic resonance imaging, computed tomography, per-rectal scintigraphy, and angiography with occlusion test. Most patients received galactose-free diet. Thirteen patients, all with intrahepatic shunts, showed spontaneous shunt closure. Symptomatic shunts were treated with embolization, ligation, or donor liver transplantation. Oral corticosteroid therapy was attempted in 4 patients with HH without benefit. We also report a novel case of secondary galactosemia at NBS. The newborn presented multiple cutaneous infantile hemangiomas (IHs). DUS showed multifocal HHs with portovenous shunts as well as a patent ductus venosus. Laboratory investigations confirmed hypergalactosemia and showed elevated bile acids. In addition to galactose-free formula, oral propranolol was started. Marked improvement of cutaneous and hepatic IHs was observed after 12 weeks. By 4.5 months cutaneous and hepatic IH involution was complete and ductus venosus obliterated. In conclusion, our review shows that secondary galactosemia on NBS can be a sign of all types of CPSS, including portovenous shunts associated with HH. In neonates with positive NBS for secondary galactosemia, DUS should be promptly performed to rule out a vascular anomaly. Finally, our case represents the first report of propranolol treatment in HH with portovenous shunts, and suggests its usefulness in accelerating HH involution with consequent shunt resolution.