Patient with Phenylketonuria and Intellectual Disability-Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome).

The authors present a case report of a boy with a classical form of phenylketonuria and Alazami syndrome. The inborn error of phenylalanine metabolism was diagnosed in the neonatal period based on population new-born screening. Despite early implementation of a low-phenylalanine diet and good biochemical control, the patient developed behavioural disorders and intellectual disability. He also presented with dysmorphic features. After long and extensive attempts to establish the genetic cause of this unusual phenotype, finally, at the age of 16 the boy was diagnosed with Alazami syndrome based on whole exome sequencing. The authors discussed the problem of neuropsychological disorders in patients with phenylketonuria and described typical clinical symptoms of Alazami syndrome. It was emphasized that the presence of one monogenic disease does not exclude the coexistence of another one.

Diagnostic and Clinical Manifestation Differences of Glucose Transporter Type 1 Deficiency Syndrome in a Family with SLC2A1 Gene Mutation.

Glucose transporter type 1 deficiency syndrome is a rare genetic disease that manifests neurological symptoms such as mental impairment or movement disorders, mostly seen in pediatric patients. Here, we highlight the main symptoms, diagnostic difficulties, and genetic correlations of this disease based on different clinical presentations between the members of a family carrying the same mutation. In this report, we studied siblings-a 5-year-old girl and a 6-year-old boy-who were admitted to a pediatric ward with various neurological symptoms. Different diagnostic procedures such as lumbar puncture, electroencephalography, and MRI of the brain were performed on these patients. Whole genome sequencing identified mutations in the SLC2A1 and GLUT1-DS genes, following which a ketogenic diet was implemented. This diet modification resulted in a good clinical response. Our case report reveals patients with the same genetic mutations having distinctive clinical manifestations.

Newborn Screening for SCID and Other Severe Primary Immunodeficiency in the Polish-German Transborder Area: Experience From the First 14 Months of Collaboration.

In 2017, in the Polish-German transborder area of West Pomerania, Mecklenburg-Western Pomerania, and Brandenburg, in collaboration with two centers in Warsaw, a partnership in the field of newborn screening (NBS) for severe primary immunodeficiency diseases (PID), mainly severe combined immunodeficiency (SCID), was initiated. SCID, but also some other severe PID, is a group of disorders characterized by the absence of T and/or B and NK cells. Affected infants are susceptible to life-threatening infections, but early detection gives a chance for effective treatment. The prevalence of SCID in the Polish and German populations is unknown but can be comparable to other countries (1:50,000-100,000). SCID NBS tests are based on real-time polymerase chain reaction (qPCR) and the measurement of a number of T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and beta-actin (ACTB) as a quality marker of DNA. This method can also be effective in NBS for other severe PID with T- and/or B-cell lymphopenia, including combined immunodeficiency (CID) or agammaglobulinemia. During the 14 months of collaboration, 44,287 newborns were screened according to the ImmunoIVD protocol. Within 65 positive samples, seven were classified to immediate recall and 58 requested a second sample. Examination of the 58 second samples resulted in recalling one newborn. Confirmatory tests included immunophenotyping of lymphocyte subsets with extension to TCR repertoire, lymphoproliferation tests, radiosensitivity tests, maternal engraftment assays, and molecular tests. Final diagnosis included: one case of T-BlowNK+ SCID, one case of atypical Tlow BlowNK+ CID, one case of autosomal recessive agammaglobulinemia, and one case of Nijmegen breakage syndrome. Among four other positive results, three infants presented with T- and/or B-cell lymphopenia due to either the mother's immunosuppression, prematurity, or unknown reasons, which resolved or almost normalized in the first months of life. One newborn was classified as truly false positive. The overall positive predictive value (PPV) for the diagnosis of severe PID was 50.0%. This is the first population screening study that allowed identification of newborns with T and/or B immunodeficiency in Central and Eastern Europe.

[Estimation of influence of congenital-adrenal hyperplasia treatment on bone mineralisation evaluated with densitometry]. / Ocena wplywu leczenia pacjentów z wrodzonym przerostem nadnerczy na mase kostna okreslona badaniem densytometrycznym

INTRODUCTION: Doses of glucocorticoids used when treating congenital adrenal hyperplasia (CAH) are larger than physiological secretion of hydrocortisone in healthy people. Optimal dosage should provide metabolic control and should not cause complications of steroid therapy. AIM OF THE STUDY: 1. Evaluation of the influence of CAH treatment on bone mineralisation established with densitometry. 2. Evaluation of steroid profiles usage, in estimation of bone mineralisation disorders risk in patients with CAH. MATERIAL AND METHODS: A total number of 28 patients with CAH, aged 2.7-27 years and receiving treatment with glucocorticoids was examined. Therapeutic coefficient and steroidal coefficient which relate to doses of hydrocortisone used were established using urine steroid profiling, which was effectuated by gas chromatography/mass spectrometry (GC/MS). Additionally dual energy x-ray absorptiometry (DXA) of the lumbar spine (L1-L4) was conducted, where bone mineral density (BMD) was established in g/cm(2), and interpreted as Z-score. RESULTS: BMD presented in Z-score, evaluated in correlation to bone age was significantly lower (p <0.01) than BMD presented in Z-score in correlation to chronological age. It was proved that greater hormonal treatment efficacy (lower steroidal coefficient or greater therapeutic coefficient) correlates with greater bone mineralisation deficits in relation to chronological age. CONCLUSIONS: 1. Greater efficiency of hormonal treatment links with larger bone mineralisation deficits in relation to CAH patients' chronological age. 2. Evaluation of steroid profiles, as one of the estimation methods for metabolic control of the disease, described by steroidal coefficient and therapeutic coefficient, allows for practical application of the above mentioned in prediction of bone mineralisation risk in patients with CAH.

[The role of ophthalmological examination in the diagnosis of gangliosidosis GM1]. / Znaczenie badania okulistycznego w rozpoznawaniu gangliozydozy GM1.

Gangliosidosis GM1 belongs to a group of lysosomal storage diseases and results from the deficiency of acidic beta-galactosidase activity. The enzyme is essential for the degradation of ganglioside GM1 and its derivatives. The disease causes multi-organ injury, however accumulation of ganglioside GM1 mainly in the brain white and gray matter results in predomination of neurological symptoms. Based on the actual knowledge--the condition is untreatable and especially in the very severe infantile form, the duration of the survival is very short. One of the characteristic symptoms of some lysosomal storage diseases, including gangliosidosis GM1, is "cherry-red" spot found in the fundus of the eye. In the publication the clinical course of gangliosidosis GM1 in two infants is presented. The value of an ophthalmological examination in the diagnosis of this rare condition has been emphasized.