Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang province / 浙江大学学报·医学版

OBJECTIVE@#To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province.@*METHODS@#Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and @*RESULTS@#A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in @*CONCLUSIONS@#The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.

Selective screening for organic acidurias and amino acidopathies in Pakistani children

Objective: To determine the frequency of organic acidurais [OA] and amino acidopathies [AA] in selected high-risk patients screened in two years

Study Design: Retrospective Observational study

Place and Duration of Study: The Aga Khan University Hospital [AKUH], Karachi, from January 2013 to December 2014

Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician

Results: Eighty-eight cases [4.7%] were diagnosed including 41 OA [46.5%], 28 AA [31.8%] and 19 others [21.5%] from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate [64.8%]. Among OA, methyl CoA mutase deficiency was diagnosed in 9 [10.2%] and was suspected in 2 [2.3%] cases. Five [5.7%] cases of MHBD [2-methyl-3-hydroxybutyryl-CoA], 4 [4.5%] each of PPA [propionic aciduria] and HMG-CoA lyase deficiency, 3 [3.4%] cases each of IVA [isovaleric aciduria], multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 [glutaric aciduria type 1] and 2 [2.3%] cases of EMA [ethyl-malonic aciduria]. AA included 8 [9.1%] cases of MSUD [maple syrup urine disease], 6 [6.8%] cases of CBS [cystathionine beta-synthetase] and UCDs [urea cycle disorders] each, 5 [5.7%] cases of hyperphenylalaninemia and 3 [3.4%] cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 [10.2%] cases of intracellular cobalamin defects, 2 [2.3%] cases each of alkaptonuria, Canavan's disease, SUCL [succinate CoA ligase] deficiency, and 1 [1.1%] case each of DPD [dihydropyrimidine] deficiency, GA-2, NKH [non-ketotic hyperglycinemia], AADC [aromatic amino acid decarboxylase] deficiency

Conclusion: This study presents frequency of OA and AA in the high-risk Pakistani pediatric population analyzed locally

Burden of genetic disorders in India.

India, like other developing countries, is facing an accelerating demographic switch to non-communicable diseases. In the cities congenital malformations and genetic disorders are important causes of morbidity and mortality. Due to the high birth rate in India a very large number of infants with genetic disorders are born every year almost half a million with malformations and 21,000 with Down syndrome. In a multi-centric study on the causes of referral for genetic counselling the top four disorders were repeated abortions (12.4%), identifiable syndromes (12.1%), chromosomal disorders (11.3%) and mental retardation (11%). In a more recent study in a private hospital the top reasons for referral were reproductive genetics (38.9%)--comprising prenatal diagnosis, recurrent abortions, infertility and Torch infections--mental retardation +/- multiple congenital anomalies (16.1%), Down syndrome (9.1%), thalassemia/haemophilia (8.8%), and muscle dystrophy/spinal muscular atrophy (8.4%). The disorders for which prenatal has been done over an 18-month-period are given. A recent study carried out in three centers (Mumbai, Delhi and Baroda) on 94,610 newborns by using a uniform proforma showed a malformation frequency of 2.03%, the commonest malformations are neural tube defects and musculo-skeletal disorders. The frequency of Down syndrome among 94,610 births was 0.87 per 1000, or 1 per 1150. Screening of 112,269 newborns for aminoacid disorders showed four disorders to be the commonest--tyrosinemia, maple syrup urine disease and phenylketonuria. Screening of cases of mental retardation for aminoacid disorders revealed four to be the commonest--hyperglycinemia, homocystinuria, alkaptonuria, and maple syrup urine disease. Metabolic studies of cases of mental retardation in AIIMS, Delhi and KEM Hospital, Mumbai, demonstrated that common disorders were those of mucopolysaccharides, lysosomes, Wilson disease, glycogen storage disease and galactosemia. It is estimated that beta- thalassemia has a frequency at birth of 1:2700, which means that about 9,000 cases of thalassemia major are born every year. Almost 5200 infants with sickle cell disease are born every year. Disorders, which deserve to be screened in the newborn period, are hypothyroidism and G-6-PD deficiency, while screening for aminoacid and other metabolic disorders could presently be restricted to symptomatic infants.