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Beijing, China

Wang Q.,Peking University | Li X.,Peking University | Ding Y.,Peking University | Liu Y.,Peking University | And 2 more authors.
Brain and Development | Year: 2015

Background: Hereditary folate malabsorption is a rare, autosomal recessive disorder of proton-coupled folate transporter deficiency resulting in folate deficiency. Left untreated, the condition can cause severe brain damage and megaloblastic anemia, leading to progressive psychomotor retardation, seizures and other neurological problems. Early diagnosis and treatment are crucial. No case has been documented yet in Mainland China until now. Methods: A Chinese girl affected by hereditary folate malabsorption was studied. The girl presented with recurrent megaloblastic anemia from the age of 7. months. Paroxysmal limbs trembling and seizures were presented from the age of three. years. Intracranial calcification was noted by CT. At her age of 5. years, mental regression, lower-extremity weakness and sleeping problems were observed. Her plasma folate decreased to 4.49. nmol/L (normal control. >. 6.8. nmol/L). Plasma total homocysteine elevated to 28.11. μmol/L (normal control. <. 15. μmol/L). Folate and 5-methylterahydrofolate in cerebrospinal fluid were significantly decreased to undetectable level. Results: On SLC46A1 gene, a novel mutation, c.1A>T (M1L), and a reported mutation c.194-195insG (p.Cys66LeufsX99) were identified, supported the diagnosis of hereditary folate malabsorption. Each parent carries one of two mutations. Folinic calcium supplement resulted in rapid clinical improvement. She is currently 6. years old with normal development and routine blood features. Conclusion: Hereditary folate malabsorption is one of the few easily-treatable inherited metabolic diseases. Measurements of folate and 5-methyltetrahydrofolate in cerebrospinal fluid are keys for the diagnosis of the patients. © 2014 The Japanese Society of Child Neurology. Source


Li X.,Peking University | Ding Y.,Peking University | Liu Y.,Peking University | Zhang Y.,Peking University | And 7 more authors.
Gene | Year: 2015

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder that affects the degradation of γ-aminobutyric acid (GABA). Only a few cases of SSADH deficiency have been documented in mainland China and prenatal diagnosis has not been performed. SSADH deficiency in four patients (three girls and one boy) from four unrelated Chinese families was detected by selective screening at the age of 50 days to 1 year. Four patients were admitted due to intractable seizures and psychomotor retardation. Their urine 4-hydroxybutyric acid was significantly elevated. Seven mutations in their ALDH5A1 gene were identified, of which the following six were novel: c.127-128insGGCCC (p.L31Pfs*62), c.615delT (p.F206Sfs*5), c.1313T>C (p.L438P), c.1568C>T (p.S523F), 1383-2delA and a 0.15-Mb deletion harboring ALDH5A1. Only one mutation, c.820C>T, had been previously reported. Three mothers of Patients 1-3 underwent amniocentesis during their third pregnancy and the fetuses were not affected by SSADH deficiency. Normal development and urine organic acid levels of the infants confirmed the prenatal diagnosis after birth. © 2015 Elsevier B.V. Source


Ding Y.,Peking University | Li X.,Peking University | Liu Y.,Peking University | Hua Y.,Peking University | And 5 more authors.
European Journal of Medical Genetics | Year: 2016

Background: Niemann-Pick disease type A (NPD-A) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency. Only a few cases have been documented in mainland China, and prenatal diagnosis has not been performed to date. In this study, the clinical and laboratory features of four Chinese patients with early-onset NPD-A were summarized. Methods: Four patients with NPD-A were the firstborns of non-consanguineous parents from four unrelated Chinese families. Bone marrow analysis, acid sphingomyelinase assay and genetic studies were performed. SMPD1 gene studies on amniocytes were performed for the prenatal diagnosis of four fetuses from three families. Results: Four patients were admitted at the age of 1-10 months due to jaundice, hepatosplenomegaly and psychomotor retardation. Liver histopathological analysis revealed glucolipid accumulation. Massive foamy histiocytes were found in the bone marrow. Acid sphingomyelinase activities of peripheral blood leukocytes were significantly decreased (4.05-21.9 nmol/h/mg protein, normal range 216.1-950.9 nmol/h/mg protein). Seven novel mutations (c.518-519insT, c.562_563insC, c.792Gdel, c.949G>A, c.1487_1499delACCGTGTGTACCA, c.1495T>C and c.1670T>C) of the SMPD1 gene were identified in four patients. Only one fetus had two mutations of the SMPD1 gene of amniocytes. The results suggested that the fetus was affected by NPD-A. The mother chose artificial abortion. The other three fetuses were not affected by NPD-A. No mutation of the SMPD1 gene was detected in the cultured amniocytes from the mothers. Postnatal genetic analysis and normal development of the three infants confirmed the prenatal diagnosis. Conclusions: Seven novel mutations associated with NPD-A were identified in the Chinese population. Prenatal diagnosis for four fetuses of three families was successfully performed by amniocyte gene analysis. © 2016 Elsevier Masson SAS. Source


Li X.,Peking University | Ding Y.,Peking University | Liu Y.,Peking University | Ma Y.,Peking University | And 5 more authors.
European Journal of Medical Genetics | Year: 2015

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China, and prenatal diagnosis has not been performed so far. In this report, 8 patients (4 girls and 4 boys) with MSUD from 8 unrelated Chinese families were diagnosed at the age of 9 days to 1 year and 8 months. The diagnosis was confirmed by serum BCAAs and genetic analyses. Among the 8 patients, only one was detected by newborn screening. The remaining 7 patients were admitted because of neurological disorders and underwent selective screening. Significantly elevated BCAAs were observed in 7 patients. One patient was diagnosed by post-mortem study. 12 mutations were found in the BCKDHA, BCKDHB and DBT genes. 11 of these mutations were novel: c.178G > T, c.491T > C, c.740A > G, c.1214_1219dupCCAACC and IVS6 +1delG in BCKDHA; c.482T > G, c.508C > T, c.767A > G, c.768C > G and IVS4,-2A > C in BCKDHB; and c.1A > G in DBT. Only one mutation, c.659C > T in the BCKDHA gene, had been previously reported. 7 patients were treated by dietary intervention and symptomatic therapy. 6 of them showed clinical improvement. The mother of one patient who died from MSUD underwent amniocentesis during her second pregnancy. The BCAAs level in her amniotic fluid was normal. Only one heterozygous mutation, IVS4,-2A > C in the BCKDHB gene, was detected in the cultured amniocytes. The results revealed that the fetus was not affected by MSUD. Normal development and the blood BCAAS profile confirmed the prenatal diagnosis after birth. Thus, we identified eleven novel mutations associated with MSUD in the Chinese population. Prenatal diagnosis of MSUD was successfully performed on one fetus by genetic analysis of the cultured amniocytes. © 2015 Elsevier Masson SAS. Source

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