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

novel clinico-biochemical score for screening of inherited metabolic diseases in children

Objective: to evaluate a novel clinico-biochemical score for screening of inherited metabolic diseases [IMDs] in children in our setup

Study Design: descriptive analytical study

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

Methodology: clinical data, preliminary biochemical investigations, plasma amino acid [PAA] and organic acid profiles [where indicated] of 354 children, aged <1 year to 12 years, referred to the study place for evaluation of suspected inherited metabolic diseases, was collected and evaluated. A clinico-biochemical score card named Rawalpindi Inherited Metabolic Diseases Score [RISc] was devised, on a scale from 1 to 10, incorporating 5 clinical and 5 important biochemical findings, and each variable was assigned a score, based on its relative frequency/risk. Each case was then assigned the RISc score and evaluated for presence or absence of any inherited metabolic disease, based on the score. This score was validated keeping plasma amino acids and organic acid profiles [in selected cases] as reference standard

Results: patients were divided into three groups, based on RISc score as low RISc [0.5-2.5], medium RISc [3.0-5.5] and high RISc [6-10]. A total of 354 cases reported in 2016 and 2017 and 33 [9.3%] were diagnosed to be having IMDs. One [3.0%] patient from low RISc, four [12.1%] from medium RISc, and 28 [84.8%] from high RISc group were found to test positive for any one IMD. High RISc group had a statistically significant higher IMD rate than the other two groups [p<0.001]. Specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and accuracy were 93%, 85%, 11.8, 0.16, 55%, 98% and 90%, respectively

Conclusion: the cost effective RISc, based on clinical data and preliminary biochemical investigations, is highly accurate in diagnosing IMDs in cost restrained setups. It is strongly suggested that the initial screening for suspected IMDs and decision for advanced laboratory testing be carried out, based on the RISc card presented in the study

Pattern of serum protein electrophoresis in various diseases

To determine the frequency and pattern of different clinical disorders on the basis of serum protein electrophoresis [SPE]. Descriptive cross sectional study. The study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, during May 2003. Five hundred SPE strips [spanning over a period of one year] of patients along-with relevant clinical information were analysed to determine the frequency and pattern of clinical disorders. Out of the 500 strips analyzed, 324 were from males [mean age: 53.5y] and 176 were from females [mean age 51.5 y]. Six major patterns were found including chronic inflammation [40.4%], acute phase response [20.8%], nephrotic syndrome [6.8%], paraproteinemia [9.2%], hepatic cirrhosis [0.8%] and normal pattern [21.18%]. Chronic inflammatory disease was found to be the most frequently observed pattern