Dyskinesia in a child: a concern for a rare neuro-metabolic disorder

A 3-year child is discussed who presented with dyskinesia, large head size, developmental delay, and recurrent infections necessitating multiple hospital admissions. The diagnosis was not made at initial presentation or even after multiple hospital admissions. An organic acidemia was suspected, based on raised ammonia and lactate levels and metabolic acidosis and the diagnosis of glutaric aciduria Type 1 was established by finding markedly elevated levels of glutaric acid and its specific metabolites on urine organic acids analysis by gas chromatography-mass spectrometry, in the setting of specific clinical features. Further supporting evidence was provided by CT scan brain showing subdural hygroma along left cerebral hemisphere causing gyral flattening and widening of sylvian fissure

Classical homocystinuria in a juvenile patient

Classical homocystinuria, also known as cystathionine beta synthase deficiency, is a rare disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites in blood and urine. A young child with homocystinuria is discussed, who presented with behavioral abnormalities, involuntary movement, mental retardation, and decreased vision since birth. The diagnosis of homocystinuria was not made at initial presentation. Subtle phenotypic features with developmental delay and MRI brain finding of bilateral medially dislocated lens, eventually provided the first indication at five years of age. Laboratory screening with plasma amino acid profile by ion exchange chromatography [IEC] showed elevated homocystine and methionine, and low cystine in plasma in the absence of vitamin B12, and folate deficiency; giving the diagnosis of classical homocysteinuria

Bilirubin interference in plasma amino acid analysis by ion exchange chromatography

Objective: To evaluate the effect of bilirubin interference on plasma amino acid analysis by Ion Exchange Chromatography [IEC]

Study Design: Cross-sectional [method validation] study

Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from August 2016 to July 2017

Methodology: Twenty non-icteric samples from paediatric patients were collected in lithium heparin tubes and analysed for amino acids on IEC-based BiochromeR 30+ Analyzer [Harvard Biosciences UK]. Baseline bilirubin levels were noted. Samples were spiked with neonatal bilirubin standard with concentration of 488.4 Mu mol/L [SpinreactR-Spain] at final concentrations of 50, 150 and 230 Mu mol/L and re-analysed for amino acids at these three concentrations

Results: Among the 20 selected patients with normal amino acid profiles, 12 [60%] were males. Majority [55%] were in age group of 1-5 years. Significant difference was observed for Arginine [p = 0.01], Histidine [p = 0.001], Isoleucine [p = 0.01], Leucine [p = 0.007], Lysine [p = 0.005], Ornithine [p = 0.03] and Phenylalanine [p = 0.02]. Mean rank of these amino acids showed decreasing trend with the increase of bilirubin concentration, and pronounced interference was identified at bilirubin level of 50 Mu mol/L. No difference was observed for alanine, citrulline, glutamic acid, glycine, methionine, proline, threonine, tyrosine, asparagine, aspartic acid, cystine, valine and tryptophan

Conclusion: Bilirubin significantly interferes with certain amino acid levels when analysis is carried out by ion exchange chromatography. A close follow-up of such patients with other biochemical tests and a repeat amino acid analysis, after jaundice is settled, is recommended to confidently rule out any possible inherited metabolic disorder in these patients

Accuracy of non-fasting lipid profile for the assessment of lipoprotein coronary risk

Objective: To determine the diagnostic accuracy of non-fasting lipid profile in the diagnosis of hyperlipidemia, taking fasting lipid profile as gold standard, in adult population

Study Design: Cross-sectional validation study

Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from July to December 2014

Methodology: One hundred seventy-five adult patients coming for fasting lipid profile were included; their non-fasting samples were taken on the next day. Patients on anti-cholesterol treatment and indoor patients were excluded. Total cholesterol [TC], high density lipoprotein-cholestrol [HDL-C], and triglycerides were measured by direct enzymatic colorimetric method by Modular p-800[registered]. Low density lipoprotein-cholesterol [LDL-C] was calculated by Friedewald's formula, but when triglyceride was greater than 4.5 mmol/l, then LDL-C was measured directly by homogenous enzymatic colorimetric method. Non-HDL-C was calculated by simple equation, i.e. TC-HDL-C

Results: Non-fasting lipid profile had 93% specificity, 51% sensitivity, 94% positive predictive value and 49% negative predictive value; and 65% accuracy with 7.28 positive likelihood ratio and 0.52 negative likelihood ratio. Non-fasting TC and non-HDL-C were significantly higher than fasting TC and non-HDL-C by mean difference of 0.2 mmol/l each with p=0.001 and p=0.004, respectively. Fasting and non fasting HDL-C are comparable to each other with mean difference of 0.01 mmol/l [p=0.745]. Receiver operating curve [ROC] of non-fasting non-HDL-C showed 0.804 [95%CI [0.738-0.870], [p=0.000] area under the curve [AUC] indicating that it was a significant test for ruling out hyperlipidemia. Bland-Altmann plot showed a significant difference between non-fasting, non-HDL-C and fasting LDL-C and non-fasting, non-HDL-C -0.087540 with bias -0.00109; therefore, these cannot be alternative to each other

Conclusion: Diagnostic accuracy of non-fasting lipid profile was found significantly higher than fasting lipid profile [p=0.004] for the assessment of lipoprotein coronary risk on the basis of non-HDL-C, which seemed to be significant test for ruling out hyperlipidemia