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1.
Elevated holo-transcobalamin in Gaucher disease type II: A case report.
Basgalupp, SP, Donis, KC, Siebert, M, E Vairo, FP, Artigalas, O, de Camargo Pinto, LL, Behringer, S, Spiekerkoetter, U, Hannibal, L, Schwartz, IVD
American journal of medical genetics. Part A. 2021;(8):2471-2476
Abstract
Gaucher disease (GD), one of the most common lysosomal disorders, is caused by deficiency of β-glucocerebrosidase. Based on the presence and severity of neurological complications, GD is classified into types I, II (the most severe form), and III. Abnormalities in systemic markers of vitamin B12 (B12 ) metabolism have been reported in GD type I patients, suggesting a higher prevalence of B12 deficiency in these patients. A 2-month-old male with GD type II was admitted to the hospital presenting jaundice, hepatosplenomegaly, and ichthyosis. At admission, cholestasis and ascites, abnormal liver function enzymes, prolonged prothrombin time, and high levels of B12 were confirmed. Analysis of biomarkers of B12 status revealed elevated B12 and holo-transcobalamin (holo-TC) levels. The B12 profile found in our patient is the opposite to what is described for GD type I patients. Holo-TC may increase in inflammatory states or due to liver diseases. In GD, the accumulation of glucocerebroside may be a trigger that initiates a systemic inflammatory reaction, characterized by macrophage activation. We suggest higher levels of holo-TC could be associated with a more severe (neuronopathic) GD, and be a biomarker of GD type II.
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2.
Aldosterone signaling defect in young infants: single-center report and review.
Wijaya, M, Ma, H, Zhang, J, Du, M, Li, Y, Chen, Q, Guo, S
BMC endocrine disorders. 2021;(1):149
Abstract
BACKGROUND Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. METHODS A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. RESULTS A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240-1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. CONCLUSION Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.
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3.
Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population.
Onay, H, Bolat, H, Kılıç Yıldırım, G, Kose, E, Kalkan Uçar, S, Aşıkovalı, S, Özkınay, F, Çoker, M
Journal of pediatric endocrinology & metabolism : JPEM. 2020;(10):1245-1250
Abstract
Objectives Fabry disease (FD, OMIM #301500) is a rare and progressive X-linked lysosomal storage disorder. FD is caused by mutations in the GLA gene on chromosome Xq22. Methods In this article, we aimed to present the largest sample of GLA mutation spectrum including common and novel variants in Turkish population. GLA gene sequence analysis was performed on the subjects who applied to the department of medical genetics with the preliminary diagnosis of FD between 2013 and 2018. Results We detected 22 different mutations as two novel [(p.F69S(c.206T>C), p.P205A (c.613C>G)] and 20 previously reported GLA mutations in 47 individuals from 22 unrelated families. These mutations included 14 missense mutations, four nonsense mutations, two small deletions, one small deletion/insertion and one small insertion. Major clinical findings of the female case with p.F69S(c.206T>C) mutation were cornea verticillata, acroparesthesia, angiokeratoma, psychiatric and gastrointestinal symptoms. Other novel mutation (p.P205A [c.613C>G]) was carried by a male case presenting gastrointestinal symptoms. Conclusions We described clinical findings of two cases that had novel mutations to provide more insight in genotype-phenotype correlation. We presented the largest mutation spectrum in Turkish population and reviewed previous mutations in this article.
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4.
Effect of dietary lysine restriction and arginine supplementation in two patients with pyridoxine-dependent epilepsy.
Yuzyuk, T, Thomas, A, Viau, K, Liu, A, De Biase, I, Botto, LD, Pasquali, M, Longo, N
Molecular genetics and metabolism. 2016;(3):167-172
Abstract
Pyridoxine-Dependent Epilepsy (PDE) is a recessive disorder caused by deficiency of α-aminoadipic semialdehyde dehydrogenase in the catabolic pathway of lysine. It is characterized by intractable seizures controlled by the administration of pharmacological doses of vitamin B6. Despite seizure control with pyridoxine, intellectual disability and developmental delays are still observed in some patients with PDE, likely due to the accumulation of toxic intermediates in the lysine catabolic pathway: alpha-aminoadipic semialdehyde (AASA), delta-1-piperideine-6-carboxylate (P6C), and pipecolic acid. Here we evaluate biochemical and clinical parameters in two PDE patients treated with a lysine-restricted diet and arginine supplementation (100-150mg/kg), aimed at reducing the levels of PDE biomarkers. Lysine restriction resulted in decreased accumulation of PDE biomarkers and improved development. Plasma lysine but not plasma arginine, directly correlated with plasma levels of AASA-P6C (p<0.001, r(2)=0.640) and pipecolic acid (p<0.01, r(2)=0.484). In addition, plasma threonine strongly correlated with the levels of AASA-P6C (p<0.0001, r(2)=0.732) and pipecolic acid (p<0.005, r(2)=0.527), suggesting extreme sensitivity of threonine catabolism to pyridoxine availability. Our results further support the use of dietary therapies in combination with pyridoxine for the treatment of PDE.
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5.
Diagnostic correlation between RET proto-oncogene mutation, imaging techniques, biochemical markers and morphological examination in MEN2A syndrome: case report and literature review.
Sovrea, AS, Dronca, E, Galatâr, M, Radian, S, Vornicescu, C, Georgescu, C
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2014;(2):389-400
Abstract
Multiple endocrine neoplasia type 2 (MEN2) is a rare autosomal dominant monogenic disorder caused mostly by missense mutations in the RET (REarranged during Transfection) proto-oncogene on chromosome 10q11.2. MEN2A represents more than 50% of all MEN2 cases, having a regular pattern with medullary thyroid carcinoma (MTC) incidence of 90-100%, bilateral pheochromocytoma (PCC) incidence of 40-50% and primary hyperparathyroidism (HPT) incidence of 10-25%. Until recently, the diagnosis of MTC was most frequently based on fine-needle aspiration of thyroid nodules, after an ultrasound examination and endocrine evaluation of serum calcitonin levels. Nowadays, RET gene screening (starting with exons 10 and 11) is a mandatory test used for identification of both symptomatic and non-symptomatic MTC carriers or for exclusion of healthy individuals from subsequent periodical clinical/biochemical screening. In this context, and in the idea of PCC preceding MTC, the early detection of germline RET mutations are highly suggestive for hereditary disease. PCC diagnosis is established in classical manner by abdominal ultrasound imaging or computed tomography confirming the presence of adrenal gland masses, elevated plasma metanephrines and normetanephrines values and histopathological examination. Additional HPT diagnosis is acknowledged by serum ionized calcium and parathormone levels. Here we report a hereditary case of MEN2A in a two-generation Romanian family, along with data presenting the importance of correlative plurifactorial diagnostic scheme in this syndrome and a short literature review.
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6.
[Primary hepatic actinomycosis concomitant with elevation of protein induced by vitamin K absence or antagonist II - report of a case].
Morita, Y, Sakaguchi, T, Shibasaki, Y, Oishi, K, Suzuki, A, Fukumoto, K, Inaba, K, Baba, S, Takehara, Y, Suzuki, S, et al
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology. 2011;(10):1735-42
Abstract
We report a case of primary hepatic actinomycosis showing elevation of serum protein induced by vitamin K absence or antagonist II (PIVKA-II). A 68-year-old man visited an affiliated hospital with a complaint of high fever and body weight loss. Hematological examination revealed severe inflammatory reactions and liver dysfunction. Abdominal CT showed a heterogeneous low density area composed of cystic and solid part. We suspected the cystic part with band-like enhancement to be a hepatic abscess and performed percutaneous transhepatic abscess drainage. Although inflammatory reactions decreased after the drainage, the solid part did not shrink and blood chemistry revealed elevation of PIVKA-II. Since we could not rule out the possibility of hepatoma, right hepatectomy was performed. Histological examination revealed actinomycetes. Although primary hepatic actinomycosis is a rare disease, it must be kept in mind in the differential diagnosis of the liver tumor.
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7.
Biomarker analysis in polycythemia vera under interferon-alpha treatment: clonality, EEC, PRV-1, and JAK2 V617F.
Steimle, C, Lehmann, U, Temerinac, S, Goerttler, PS, Kreipe, H, Meinhardt, G, Heimpel, H, Pahl, HL
Annals of hematology. 2007;(4):239-44
Abstract
Three consecutive polycythemia vera (PV) patients were analyzed before and during pegylated-interferon (rIFNalpha) treatment for the following markers: (1) granulocyte and CD34(+) cell clonality, (2) Jak2V617F expression, (3) PRV-1 mRNA overexpression, and (4) Epo-independent colony (EEC) growth. Before rIFNalpha therapy, all patients displayed clonal hematopoiesis, 100% Jak2V617F expression as well as PRV-1 overexpression, and EEC growth. After rIFNalpha treatment, all three patients demonstrated polyclonal hematopoiesis. Nonetheless, Jak2V617F expression, PRV-1 overexpression, and EEC-growth remained detectable, albeit at lower levels. We conclude that reemergence of polyclonal hematopoiesis after rIFNalpha treatment may be achieved in a substantial proportion of patients. However, this does not constitute elimination of the PV clone. These data demonstrate the usefulness of novel markers in monitoring minimal residual disease and caution against discontinuation of rIFNalpha treatment after hematologic remission. Long-term follow-up of large patient cohorts is required to determine whether rIFNalpha treatment can cause complete molecular remissions in PV.
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8.
MMP-2 assessment as an indicator of wound healing: A feasibility study.
Karim, RB, Brito, BL, Dutrieux, RP, Lassance, FP, Hage, JJ
Advances in skin & wound care. 2006;(6):324-7
Abstract
OBJECTIVE Evaluate the feasibility of assessment of fibroblast matrix metalloproteinase-2 (MMP-2) expression as an indicator of wound healing in wounds that change from chronically inert to actively healing. METHODS Phase II feasibility study of 4 patients with nonhealing wounds (duration, > or = 3 months; surface area, > or = 1 cm). Wounds were treated with a dressing impregated with oak bark extract (DerMax) and evaluated weekly; biopsies were performed every 2 weeks until wound healing. RESULTS Therapy-induced wound healing and immunohistochemical measurements of MMP-2 expression paralleled the clinical characteristics of wound healing. CONCLUSION MMP-2 expression offers a reliable indicator for clinical wound healing induced by DerMax treatment.