Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.
Child ; Humans ; Exons ; Glycogen Storage Disease/genetics* ; Hepatomegaly/genetics* ; Mutation ; Phosphorylase Kinase/genetics* ; Male ; Female

A 2-year-old boy was admitted into the hospital because of cough and fever. Lymph node tuberculosis was noted when he was 2 months old and he was subsequently hospitalized several times because of cough and fever. After hospitalization the laboratory examination showed an increased eosinophia level in blood. The immune function tests shows decreased levels of IgG, IgA, and IgM. The patient had no response to anti-tuberculosis, anti-bacterial, and anti-fungal treatment, resulting in recurrent fever and progressive enlargement of the liver and spleen. Jam-like stools were noted 35 days after admission. B ultrasonography showed suspected intussusception. Laparotomy, reduction of intussusception and ileocecum angioplasty, biopsies of intestinal wall nodules and lymphoglandulae mesentericae, and hepatic biopsy were then performed under general anesthesia. The patient eventually died because of postoperative severe liver damage, disseminated intravascular coagulation and electrolyte disorder. Both the blood culture and hepatic biopsy tests showed Penicillium marneffei infecton. Immunodeficiency gene test was performed on the patient, his bother and their parents. T→G base substitution mutation (IVS1-3 T→G) in the CD40L gene was found in the patient. X-linked hyper-IgM syndrome was thus diagnosed in the patient. His mother was a carrier of the mutated CD40L gene, but his father was normal in the gene test. Hemizygous mutation in the CD40L gene was found in both the patient and his bother.
CD40 Ligand ; genetics ; Child, Preschool ; Eosinophilia ; etiology ; Fever ; etiology ; Hepatomegaly ; etiology ; Humans ; Hyper-IgM Immunodeficiency Syndrome ; diagnosis ; genetics ; Male ; Mutation ; Recurrence ; Splenomegaly ; etiology

We report an autopsy case of congenital monoblastic leukemia that developed in monozygotic twins. The twin presented with progressive hepatosplenomegaly at 4 weeks after birth. One twin died of massive bleeding and hypovolemic shock before the treatment started. At autopsy, the liver was diffusely enlarged and showed a diffuse whitish discoloration except for the subcapsular and perivenular areas. Microscopic examination disclosed infiltration of histiocyte-like atypical cells along the sinusoids and portal areas of the liver. Spleen, lymph nodes and choroid plexus were also infiltrated by the tumor cells. However, bone marrow involvement of the tumor was minimal although multifocal. On immunohistochemical staining, these atypical cells were reactive for CD68 (PGM-1) and lysozyme, suggesting that the tumor cells might have been derived from mono- histiocyte. Cytogenetic study revealed 9;11 translocation, which is frequently associated with acute monoblastic leukemia. To the best of our knowledge, this is the first report of congenital monoblastic leukemia of monozygotic twins in Korea.
*Chromosomes, Human, Pair 11 ; *Chromosomes, Human, Pair 9 ; *Diseases in Twins/genetics ; Fatal Outcome ; Female ; Hepatomegaly/complications/genetics/pathology ; Human ; Infant, Newborn ; Leukemia, Monocytic, Acute/complications/*congenital/genetics/pathology ; Liver/pathology ; Splenomegaly/complications/genetics/pathology ; *Translocation (Genetics) ; *Twins, Monozygotic/genetics

Glycogen storage disease type III (GSD III) is a very rare disorder caused by a deficiency in the activities of glycogen debranching enzymes (amylo-1-6-glucosidase and 4-alpha-glucanotransferase). GSD III is characterized by the accumulation of abnormal glycogen in the liver and skeletal muscle. The primary clinical manifestations are hepatomegaly, fasting hypoglycemia, and hyperlipidemia in infants. We report a rare case of GSD III in an adult. A 52-year-old woman presented to our clinic due to dyspnea on exertion, severe general weakness, and hepatomegaly. Hypertrophic cardiomyopathy was diagnosed based on echocardiogram findings. The microscopic findings of liver and skeletal muscle biopsies were consistent with the diagnosis of GSD. DNA analysis prompted by clinical and pathologic findings led to a definitive diagnosis of GSD IIIa. Diet therapy with cornstarch was started, and the patient was followed closely. This represents the first reported case of GSD IIIa diagnosed in an adult in Korea.
Amino Acid Substitution ; Base Sequence ; Female ; Glycogen Storage Disease Type III/*diagnosis/genetics/pathology ; Hepatomegaly/genetics ; Heterozygote ; Humans ; Liver/pathology ; Middle Aged ; Molecular Sequence Data ; Muscle, Skeletal/pathology ; Starch/therapeutic use ; Tomography, X-Ray Computed