Objectives: Fructose 1,6 bisphosphatase (FBPase) deficiency is a rare autosomal recessively inherited metabolic disease. It is encoded by FBP1, and the enzyme catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose 6-phosphate. Patients with recurrent episodes of metabolic acidosis, hypoglycemia, hypertriglyceridemia, and hyperketonemia are present. Methods: In this study, we describe the clinical, biochemical, and molecular genetic features of six unrelated Turkish patients from six different families who were genetically diagnosed with FBPase deficiency in our clinic between 2008 and 2020. Their clinical and laboratory data were collected retrospectively. Next-generation sequencing (NGS) was performed for the molecular genetic analysis. Results: All patients were hospitalized with recurrent hypoglycemia and metabolic acidosis episodes. Three out of six patients were presented in the neonatal period. The mean age at diagnosis was 26 months. NGS revealed a known homozygous gross deletion including exon 2 in three patients (50%), a known homozygous c.910_911dupTT pathogenic variant in one patient (16%), a novel homozygous c.651_653delCAGinsTAA likely pathogenic variant, and another novel homozygous c.705+5G>A splice site variant. Leukocyte FBPase analysis detected no enzyme activity in the patient with homozygous c.705+5G>A splice site variant. Conclusions: We identified two novel mutations in this study. One of them is a splice site mutation which is five bases downstream of the exon, and the other one is an indel mutation. Both of the splice site and indel mutations are exceedingly rare in FBP1, and to the best of our knowledge, there are second splice site and indel variants reported in the literature. Exon 2 deletion is the most common mutation consistent with the previous reports in Turkish patients. FBPase is a frequent cause of hypoglycemia and metabolic acidosis, and the widespread use of molecular genetic analysis would contribute to the enlightenment of advanced genetic factors and possible genotype/phenotype correlation.

Objectives: Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. Case presentation: The patient was started to the treatment with peroral acetazolamide however the lesion did not regress but a new lesion appeared then we added sevelamer and topical sodium thiosulfate treatment for three months. After the three months of the combination treatment the lesions, there were no pain, no hyperphospahtemia regression/disappearance of the lesions. Conclusions: This combination treatment or topical sodium thiosulfate use only may be a novel treatment strategy for the patients prospective controlled trials are needed.

Background. Fucosidosis is a rare, autosomal recessive lysosomal storage disease caused by alpha L- fucosidase enzyme deficiency in all tissues. Here, we identify a patient with a novel homozygous pathogenic variant and atypical clinical findings and summarized the clinical and molecular features of Turkish patients reported in the literature and present. Case. The patient was born to consangineous parents at the 28th week of gestation. He had developmental delay that was attributed to prematurity. At he age of 2.5 years, brain magnetic resonans imaging revealed hyperintensities of symmetrical periventricular, subcortical, centrum semiovale and corona radiata regions on T2 and FLAIR weighted images. He developed seizures and showed developmental regression at he age of 3,5 years. Beside, coarse facial features and hepatomegaly were detected on phsyical examination. Lysosomal enzyme analysis revelaed alfa fucosidase deficiency and molecular genetic analysis identified a novel homozygous pathogenic p. Lys431 fs variant in FUCA1 gene. Conclusions. In Turkish patients no distinguishable clinical and radiologic finding could be established. Molecular analysis was performed in few patients. Increasing of molecular and biochemical facilities might enable to make diagnosis and increase the prevalence of the disease in countries with high rate of consanguineous marriages. Moreover, it will provide genetic counseling, and enlighten the therapeutic effects of hematopoietic stem cell transplantation.

Objectives Enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA) has changed the fatal course of infantile Pompe disease, however, development of anti rhGAA antibodies and infusion-associated reactions (IAR) restrict the tolerability and effectiveness of the treatment. Case presentation We describe a successful concomitant immune tolerance induction (ITI) and desensitization protocols in a cross-reactive immunologic material (CRIM) negative 7-month-old male patient. At the age of 5 months and eighth dose of the ERT, the patient developed IAR and his rhGAA specific IgE was negative however, his rhGAA specific IgG titer was as high as 12,800. ITI therapy to suppress antibody formation and a desensitization protocol was devised to be given concomitantly. At the end of 5-week therapy, his fatigue and weakness improved profoundly and a control antidrug antibody level decreased at 800. At the time of the patient’s follow up, he was still on ERT with desensitization at the age of 15 months without any reactions. Conclusions This is the first report in the literature applying concomitant ITI and desensitization protocols in a CRIM negative infantile-onset Pompe disease patient successfully, hence the importance of the case.

Background. Hepatic glycogen storage diseases are a group of diseases manifesting mainly with hypoglycemia and hepatomegaly. The patients require frequent daytime and nocturnal feedings. Hypoglycemia may cause sensorineural hearing loss and nocturnal feeding is a risk factor for the development of gastroesophageal reflux that may cause chronic otitis media and hearing loss consequently. We aimed to determine the prevalence and characteristics of hearing loss in hepatic glycogen storage diseases. Methods. A total of 24 patients with hepatic glycogen storage disease (15 glycogen storage disease type I and 9 non type I) and 24 age/sex matched healthy controls were enrolled in the study. Pure tone audiometer, (ABR) tests were applied to all participants.Results. Hearing loss was determined in 17/24 patients (12 glycogen storage disease type I and 5 non type I) with pure tone audiometer. Interpretation of all the findings revealed a total of 8 patients had conductive and 9 had mixed hearing loss. All parameters were significantly different than the control group.Conclusions. This is the first study to comprehensively assess the auditory functions of patients with hepatic glycogen storage disease. Audiological findings determined a significantly increased prevalence of conductive/ mixed type hearing loss in the patient group which is a new finding in the literature. Further studies with extended patient numbers are required to enlighten the underlying pathophysiology.

Objectives GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder caused by beta-galactosidase deficiency encoded by GLB1. It is mainly characterized by progressive neurodegeneration due to accumulation of glycosphingolipids in central nervous system and classified into 3 forms according to the age of onset and severity of symptoms. Case presentations In this study, we described the demographic, clinical, molecular, biochemical characteristics of 4 patients from 3 unrelated families diagnosed with GM1-gangliosidosis. The ages of the patients included in the study were between 5 months and 10 years old and all were male. All families had third degree consanguinity. Two of the patients were diagnosed as infantile type and the other two siblings were diagnosed as juvenile type. Infantile type patients had coarse facial appearance, developmental delay and early neurodegeneration. Juvenile type patients had mild motor and cognitive developmental delays at the beginning, but they did not have coarse facial features. Cherry-red macula and cardiac involvement were detected in only one infantile patient, while hepatomegaly was present in both infantile type patients. Beta galactosidase enzyme levels were extremely low in all patients and two novel variants were identified in GLB1. Conclusions In this study, we identified four patients with different phenotypic features and two new mutations. GM1 gangliosidosis shows clinical heterogeneity according to age of onset. In some patients, developmental delay can be seen before the loss of gained functions. Therefore, this disorder should be kept in mind in patients with developmental delay who have not yet started neurodegeneration. There is no curative treatment for the disease yet, but ongoing gene therapy studies are promising for curing the disease in the future.