Clinical Spectrum of Propionic Acidaemia

Hindawi Publishing Corporation Journal of Nutrition and Metabolism Volume 2013, Article ID 975964, 6 pages http://dx.doi.org/10.1155/2013/975964 Clinical Study Clinical Spectrum of Propionic Acidaemia Muhammad Rafique Department of Child Health, College of Medicine, King Khalid University, Abha 61321, Saudi Arabia Correspondence should be addressed to Muhammad Rafique; Received 21 March 2013; Accepted 12 September 2013 Academic Editor: H. K. Biesalski Copyright © 2013 Muhammad Rafique. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. To evaluate the clinical features, physical findings, diagnosis, and laboratory parameters of the patients with propionic acidaemia (PA). Methods. The records of diagnosed cases of propionic acidaemia were reviewed, retrospectively. Results. Twentysix patients with PA had 133 admissions. The majority (85%) of the patients exhibited clinical manifestations in the 1st week of life. Regarding clinical features, lethargy, fever, poor feeding, vomiting, dehydration, muscular hypotonia, respiratory symptoms, encephalopathy, disturbance of tone and reflexes, and malnutrition were observed in 51–92% admissions. Metabolic crises, respiratory diseases, hyperammonaemia, metabolic acidosis, hypoalbuminaemia, and hypocalcaemia were observed in 30–96% admissions. Pancytopenia, ketonuria, hypoproteinemia, hypoglycaemia, and mildly disturbed liver enzymes were found in 12–41% admissions. Generalised brain oedema was detected in 17% and cerebral atrophy in 25% admissions. Gender-wise odd ratio analysis showed value of 1.9 for lethargy, 1.99 for respiratory diseases, 0.55 for anaemia, and 1.82 for hypocalcaemia. Conclusion. Propionic acidaemia usually presents with wide spectrum of clinical features and disturbances of laboratory parameters in early neonatal age. It is associated with significant complications which deteriorate the patients’ quality of life. Perhaps with early diagnosis of the disease and in time intervention, these may be preventable. 1. Introduction Propionic acidaemia (PA) is a rare autosomal recessive metabolic disease. About 80% are early onset cases (who are diagnosed within three months of age) which classically present in the neonatal period with lethargy, vomiting, refusal to feed, hypotonia, and less frequently with dehydration and seizures [1, 2]. Some patients show milder symptoms and long survival rate, associated with chronic late onset form [3]. In the individuals with PA, serious health problems can be triggered by prolonged fasting, fever or infections, and high protein diet leading to accumulation of toxic substances [2]. Hyperammonaemia is the most common presentation found in 88%, patients [2]. The disease is also characterized by repeated episodes of metabolic acidosis, occasionally seizures, coma, and cerebellar haemorrhages [4]. Hypoglycaemia is a commonly described finding during metabolic decompensations but rarely hyperglycaemia and decreased bone density have also been reported [5]. Commonly observed viral infection and bone marrow suppression with neutropenia and thrombocytopenia in patients with PA might be lethal [3, 6]. There are few reports [8] of presentation of patients with PA from Kingdom of Saudi Arabia (KSA), yet none is available from south-west region of KSA. So, this study was carried out to find out the clinical features, physical findings, laboratory parameters, and diagnosis of the diseases with which the patients with PA were admitted to the hospital. 2. Methods The study was conducted in a tertiary care, referral, public hospital, during the period of January 2001–December 2012, retrospectively. The records were ascertained of all admitted Saudi patients in the department of Paediatrics with confirmed diagnosis of PA (on basis of high propionylcarnitine level in blood, detected by tandem mass spectrometry, high level of propionate in urine, enzyme analysis, and genetic studies). All cases were reviewed for the variables of: age of the patients at diagnosis and present age, family history, clinical features, and detail of admissions. Weight and height/ length of the patients were noted and their percentages of normal for age of Saudi children were calculated. Under nutrition/wasting (weight < normal for age) percentage was 2 Journal of Nutrition and Metabolism Table 1: Data of 26 patients with PA. Variable of patients Male Female Mean age in yr Consanguinity of parents H/O of PA in siblings H/O NICU admission No. of deceased patients Time of clinical onset/diagnosis 1st week of life (early onset) 2nd week—3months (early onset) >3 months of age (late onset) Diagnosis age (range: 2 day–1yr) Mean % of weight for age Mean % of height/length for age 𝑛 (%)/mean (SD) 16 (61.5) 10 (38.5) 2.85 [4.8] 24 (92.3) 10 (38.5) 17 (63.4) 2 (7.7) 22 (84.6) 2 (7.7) 2 (7.7) 0.13 [0.3] 72.4 [17.1] 90.7 [8.8] Variables of patients No. of admission/patient Frequency of admission/yr Early onset cases Late onset cases Cerebral palsy Seizures Hypotonia Hyporeflexia Hypertonia Hyperreflexia Patients were On NG/G tube feeding On home oxygen therapy Look after in social home 𝑛 (%)/mean (SD) 5.1 [6.5] 4.2 [3] 5.5 [6.7] 2 4 (15.4) 12 (46.2) 11 (42.3) 4 (15.4) 4 (15.4) 9 (34.6) 4 (15.4) 2 (7.7) 2 (7.7) Values are given in 𝑛 (%) or mean (SD); H/O: history of, NICU: neonatal intensive care unit, NG/G: nasogastric/gastrostomy tube. calculated and categorised according to Gomez classification of malnutrition. Short stature/stunting (height < normal for age) percentage was calculated and categorised according to Waterlow classification of malnutrition [10]. The records were also reviewed for biochemical analysis, other relevant investigations, and diagnosis of the presenting diseases with which those patients of PA were admitted. The data were analyzed by using SPSS version 17. One sample 𝑡-test (Table 2) was applied to find out the significance of important variables which produced significant impact on patients of PA. The study was approved by the Research Ethical Committee of King Khalid University, Abha, KSA (Record no. 2012-10-08). 3. Results Our study group included 26 patients with 133 admissions. Their (mean ± SD) age at last admission was observed to be 4.3 ± 4.7 years. Table 1 demonstrates demographic characteristics of patients with PA. Regarding diagnosis of PA, tandem mass spectrometry results showed mean propionylcarnitine level of 18.8 ± 2.7 umol/L (normal: <4.33) and mean C3/C2 ratio was 1.9 ± 0.2 (normal: <0.1). In early onset cases, mean age was 2.95 ± 4.95 yr (range: 3 days–14 yr) and mean age of surviving patients was 2.24 yr (range: 3 days–12.5 yr). Frequency of admissions/year in those cases was 5.5 ± 6.7. Mean age of two late onset cases was 1.05 yr; their hospital admissions were comparatively infrequent (2/yr) and no l (...truncated)