Is diagnosing patients with Organic Acidurias and Aminoacidopathies enough? Conundrums of a low middle-income country.

OBJECTIVE: This study was done to determine the factors responsible for non-treatment of inherited metabolic disorders (IMDs) requiring food for special medical purposes (FSMPs) in Pakistan. METHODS: A descriptive cross-sectional study was conducted by Departments of Pediatrics & Child Health and Pathology & Laboratory Medicine, Aga Khan University. Patients diagnosed with IMDs from January 2013 to December 2016 requiring FSMPs were surveyed after a year of initial diagnosis to collect the details of treatment advised, mortality status, and reasons of non-treatment, including not prescribed by physician, non-acceptance by family, non-availability or non-affordability. RESULTS: Over four years period, 311 patients were identified with IMDs; Median age of patients was 1.0 yrs (0.0.2-3.65) with 54% (n=168) being male. Of the total 38.2% (n=119) required FSMPs, 9% (n=28) patients were excluded due to unavailability of diagnostics information. Parents of 58 patients requiring FSMPs out of 119 participated in survey. The leading causes of non-treatment were, FSMPs not prescribed by physicians (n= 30, 51.7%) followed by non-affordability (n=23, 39.6%), families' unacceptance in (n=9, 18%) patients, non-availability of FSMPs (n=2, 3.4%) and early death of patient (n=1, 1.7%). CONCLUSION: The main factors responsible for non-treatment of FSMPs requiring IMDs were non-prescription by physician and non-affordability.

Retrospective Study of Patients with Hyperphenylalaninemia- Experience from a Tertiary Care Center in Pakistan.

OBJECTIVE: To assess the clinical and biochemical features as well as outcome of hyperphenylalaninemia patients. Methods: The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2013 to February 2017 of plasma amino acid analysed at the Biochemical Genetic Laboratory of patients with phenylalanine levels >120 umol/L. Medical charts of patients registered with the Metabolic Clinics were reviewed, while outside referrals were contacted by telephone to collect data on a pre-structured questionnaire. Data was analysed using SPSS 21. RESULTS: Of the 18 patients, 13(72%) were males. Overall median age was 606 days (interquartile range: 761) and median phenylalanine levels were 1280 (interquartile range: 935) umol/L. Phenylalanine hydroxylase deficiency was present in 5(28%) patients while 3(16.6%) had defects in the metabolism or regeneration of tetrahydrobiopterin. The most common clinical features was intellectual deficit and seizures 14(78%) each, followed by lighter hair colour 10(55.5%) and hypotonia 11(61%). High treatment cost was the leading reason for cessation of therapy in 7(39%) followed by refusal by patient's family 5(28%). CONCLUSIONS: Most hyperphenylalaninemia cases were diagnosed late when intellectual disability had already developed.

Diagnostic dilemma of patients with methylmalonic aciduria: Experience from a tertiary care centre in Pakistan.

OBJECTIVE: To determine the frequency of disorders leading to methylmalonic acidurias. METHODS: This cross-sectional study was conducted from January 2013 to April 2016 at the Aga Khan University Hospital, Karachi, and comprised patients diagnosed with methylmalonic acidurias based on urine organic acid analysis. Clinical history and biochemical data was collected from the biochemical genetics laboratory requisition forms. Organic acid chromatograms of all the subjects were critically reviewed by a biochemical pathologist and a metabolic physician. For assessing the clinical outcome, medical charts of the patients were reviewed. SPSS 19 was used for data analysis. RESULTS: Of the 1,778 patients 50(2.81%) were detected with methylmalonic acidurias. After excluding patients with non-significant peaks of methylmalonic acidemia, 41(2.31%) were included in the final analysis. Of these, 20(48.7%) were females, while the overall median age was 11.5 months (interquartile range: 6-41.5). On stratification by type of disorders leading to methylmalonic acidurias, 9(22%) had methylmalonic acidemia, 12(29%) had Cobalamin-related remethylation disorders, nonspecific methylmalonic acidurias in 16(39%), while 2(5%) each had succinyl coenzyme A synthetase and Vitamin B12 deficiency. respectively. CONCLUSIONS: Screening tests, including urine organic acid, provided valuable clues to the aetiology of methylmalonic acidurias.