Early diagnostic clues of mucolipidosis type II: Significance of radiological findings.

Mucolipidosis type-II (ML-II) is an ultra-rare disorder caused by deficiency of N-acetylglucosaminyl-1-phosphotransferase enzyme due to biallelic pathogenic variants in GNPTAB gene. There are a few known about the natural history of ML-II. In this study, we presented the natural course of 24 patients diagnosed with ML-II. Mean age at diagnosis was 9.3 ± 5.7 months. All patients had coarse face, developmental delay, and hypotonia. The mean survival time was 3.01 ± 1.4 years. The oldest patient was 6.5 years old. Twelve patients died due to lung infection and respiratory failure. We observed early and significant radiological findings of ML-II were different from typical dysostosis multiplex such as femoral cloaking, rickets-like changes, and talocalcaneal stippling. These are significant findings observed in the fetal or newborn period which is considered to be highly characteristic of ML-II and disappears in the first year. Cloaking, rickets-like changes, and stippling were not observed in patients older than three months of age and this suggests that these findings disappear within the first year. These radiological features can be used as important clues for diagnosis. We detected eight different pathogenic variants in GNPTAB gene, three of them were novel.

Actions speak louder than words: Home visits and its effect on dietary adherence in patients with phenylketonuria.

AIM: Phenylketonuria (PKU) is an inherited metabolic disorder in which accumulation of phenylalanine (Phe) leads to poor neurological outcomes without treatment. Dietary therapy is the main treatment and nonadherence is associated with elevated blood Phe levels and correspondingly poor neuropsychiatric outcomes. This study aimed to examine the effect of home visits on blood Phe levels in PKU patients. METHODS: Sixty-five paediatric PKU patients who were on low-phenylalanine diet were visited monthly at home for 6 months. At each visit, dietary education was provided, patients' height and weight were measured and blood samples were collected. RESULTS: Twenty-eight (43.1%) patients had classic PKU and 37 (56.9%) had moderate PKU. Blood Phe levels decreased statistically significant at first, second, fifth, and sixth months compared with screening visit. Blood Phe levels in moderate PKU patients decreased significantly at the last visit unlike classic PKU patients. A significant decrease in blood Phe levels was observed in patients older than 10 years. Anthropometric parameters improved. CONCLUSIONS: Dietary nonadherence is the main treatment failure in PKU. Home visits for education are a promising way to improve treatment outcomes by providing quality education, better assessment, and correction of mistakes but they should be ongoing and supported by different interventions that address patients' special needs.

Expanding the phenotypic landscape of Gaucher disease type 3c with a novel entity - Transient neonatal cholestasis.

Gaucher disease (GD) is the most frequent lysosomal storage disorder due to biallelic pathogenic variants in GBA gene. Only homozygous D409H variant has been associated with the cardiovascular phenotype which is also known as Gaucher disease type 3c. In this descriptive study, we presented phenotypic heterogeneity and a novel clinical finding among 13 patients with GD type 3c. Patients presented with varying degrees of cardiac valve and/or aortic calcifications (84,6%) and corneal opacities (76,9%) in addition to visceral (100%), hematological (92,3%), neurological (92,3%), and skeletal (30%) manifestations. Also, cervical dystonia (38,4%) and psychiatric disorders (46,1%) were not infrequent entities with respect to neurological involvement in GD type 3c. In this report, we highlight transient neonatal cholestasis (38,4%) as a novel finding in GD type 3c. Neonatal cholestasis is a finding associated with Gaucher type 2, but transient neonatal cholestasis has not been reported in GD patients, so far. The clinical features of GD type 3c are highly heterogeneous, from disease severity or age of onset to disease progression. Also, we concluded that phenotypic spectrum may be associated with age at onset of clinical symptoms. As, patients presenting in infancy or childhood had mainly visceral and hematological involvement and patients presenting in adolescence and adulthood had mainly cardiac, neurological involvement, and psychiatric behavioral disorders. Identifying the heterogeneous clinical course of these patients in this fatal disease, may lead a sufficient understanding of the pathophysiology which will enable targeted therapeutic interventions.

Evaluation of bone health in patients with mucopolysaccharidosis.

INTRODUCTION: This study aimed to evaluate the relationship between clinical findings, height and weight standard deviation scores, 25-hydroxyvitamin D3 (25(OH)D3) level, and dual-energy X-ray absorptiometry (DXA) results in patients diagnosed with mucopolysaccharidosis (MPS), where effective current treatments such as enzyme replacement therapy (ERT) can be accessed. MATERIALS AND METHODS: 25(OH)D3 level was measured in 126 patients with MPS (17 with MPS I, 14 with MPS II, 18 with MPS III, 33 with MPS IVA, and 44 with MPS VI; 24-524 months). DXA was performed in 45 of these patients (8 with MPS I, 4 with MPS II, 4 with MPS III, 12 with MPS IVA, and 17 with MPS VI; 62-197 months; all patients were under 18 when DXA was performed) to assess bone mineral density (BMD) of the lumbar spine. RESULTS: In total, 67.5% patients had a short stature, and 50% of them were underweight for their age. Of the patients, 13.5% were immobile, 28.6% had 25(OH)D3 deficiency, and 30.2% had an insufficient level of 25(OH)D3. BMD z score of 45 patients was - 2.5 ± 1.7. In 40% patients, it was < - 2. However, after correction for height-for-age z score (HAZ), HAZ-adjusted BMD z score was - 0.1 ± 0.9. In 2.2% patients, it was < - 2. CONCLUSION: The low BMD z score prevalence reported with DXA was misleadingly higher in children with MPS and short stature. To prevent exposure to unnecessary antiresorptive treatments in these children, the effect of severe short stature and bone geometry on DXA measurements should be considered; further studies on bone health are warranted.

Glycogen storage disease type XII; an ultra rare cause of hemolytic anemia and rhabdomyolysis: one new case report.

OBJECTIVES: Aldolase A deficiency also known as glycogen storage disease (GSD) XII, is an ultra rare autosomal recessively inherited GSD, associated with hemolytic anemia and rhabdomyolysis. CASE PRESENTATION: Here, we first report a patient with dermatological findings, hemodialysis requirement for rhabdomyolysis, and a novel likely pathogenic c.971C>T (p.A324V) mutation in the ALDOA gene. CONCLUSIONS: Episodes of rhabdomyolysis can be triggered by febrile illnesses and catabolic processes. Diagnosis should be confirmed by the mutation analysis of ALDOA gene. Treatment includes management of hemolytic anemia and administration of antipyretics during febrile episodes to avoid hemolysis and rhabdomyolysis.