The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency.

BACKGROUND: Glycogen synthase deficiency, also known as glycogenosis (GSD) type 0 is an inborn error of glycogen metabolism caused by mutations in the GYS2 gene, which is transmitted in an autosomal recessive trait. It is a rare form of hepatic glycogen storage disease with less than 30 cases reported in the literature so far. The disorder is characterized by fasting hyperketotic hypoglycemia without hyperalaninemia or hyperlactacidemia. It is a glycogenosis with lack of liver glycogen synthesis, therefore hepatomegaly is not observed in patients with glycogen synthase deficiency. Symptoms of fasting hypoglycemia in patients with glycogen storage disease type 0 (GSD0) usually appear for the first time in late infancy when weaning from overnight feeds. Seizures associated with low blood glucose may also occur, but they are rare. Clinical management is therefore based on frequent meals composed of high protein intake during the day and addition of uncooked cornstarch in the evening. CASE PRESENTATION: Herein we report three new cases of liver glycogen synthase deficiency (GSD0). The first patient presented at the 4 years of age with recurrent hypoglycemic seizures. The second patient who is the brother of the first patient presented at 15 months with asymptomatic incidental hypoglycemia. Glucose monitoring in both patients revealed daily fluctuations from fasting hypoglycemia to postprandial hyperglycemia and lactic acidemia. A third patient was consulted for ketotic hypoglycemia and postprandial hyperglycemia at the 5 years of age. CONCLUSIONS: Genetic analyses of the siblings revealed homozygosity for mutation c.736C>T on the GYS2 gene confirming the diagnosis. The third patient was found to be homozygous for c.1145G>A. GSD0 is more common than previously assumed. Recognition of the variable phenotypic spectrum of GSD0 and routine analysis of GYS2 are essential for the correct diagnosis.

Vitamin B12 Deficiency in Infants.

OBJECTIVE: To determine different clinical presentations of vitamin B12 deficiency in infants. METHODS: Infants at the age of 1-20 mo admitted to infancy clinic of authors' hospital between January 2011-2013 with various clinical presentations due to vitamin B12 deficiency were included in the study. Hospital records of all the patients were evaluated by means of history, physical, laboratory, imaging examinations and treatment. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. RESULTS: A total of 20 patients with a mean age of 6.65 ± 4.5 mo were included in the study. The weight and height were below the third percentile in four patients. The most common symptoms of the patients were; infections in 30 %, pallor in 25 %, hypotonia and neuro-developmental delay in 25 %, refusal to solid food or to suck in 20 %, failure to thrive in 15 %, fatigue in 10 %. Twenty-five percent of patients had neurologic signs and symptoms. Anemia was found in 16/20 (80 %) patients. Three (15 %) patients had leukopenia, 7 (35 %) had neutropenia, 2 (10 %) patients had thrombocytopenia. All of the mothers had vitamin B12 deficiency. All of the patients were fed with breast milk. Cyanocobalamin was administered to all the patients and mothers. After the treatment, clinical and laboratory findings of all the patients improved. CONCLUSIONS: Vitamin B12 deficiency should be considered in the differential diagnosis of some hematological, neurological, and gastrointestinal disturbances of infants.