Introduction

Inborn errors of metabolism (IEM) are individually rare, but collectively numerous. Their protean clinical presentations in children with substantial morbidity and mortality pose a formidable challange to the practicing Pediatrician [1]. The recent availability of Tandem mass spectrometry and Gas chromatography has enabled the diagnosis of amino acid disorders, organic acidemias and fatty acid oxidation disorders to a greater extent. In India, the reported prevalance of IEM is 1 in 2497 newborns [2] although the true pan India prevalence still remains unknown [3]. To get a better estimate of number of patients with rare disorders, ICMR has launched the “The Indian Rare disease Registry” in 2017. India having a relatively high birth rate of approximately 25 million babies born every year and also a higher prevalence of consanguineous marriages across the country, the occurrence of IEM may be even higher. There is paucity of data from south India with regard to the clinical spectrum of IEM except for a few isolated case reports/series and hence authors studied the clinical spectrum and outcome of IEM in children.

Material and Methods

This prospective study was conducted in the Metabolic Clinic of Kanchi Kamakoti CHILDS Trust Hospital, Chennai during the period June 2017 till May 2018 and the study was approved by the Institutional Ethics Committee. During this period, 31 children aged from newborn to eighteen years in whom the diagnosis of IEM was newly established were included for the study. Their relevant clinical, biochemical, imaging, molecular genetic, treatment and follow-up details were analysed. Children with suspected IEM, sepsis and in whom the diagnosis was not established during the said period were excluded.

The data collected were tabulated and analysed by using the Microsoft office excel 2007. The data are expressed in form of numbers and percentages.

Results

During this period, 31 children were diagnosed with IEM out of 1539 hospital admissions, accounting for 2% of hospital admissions. Of the 31 children, 3 were admitted in to ICU and the rest were admitted in ward either for diagnoses or treatment. Of the 31 children, 18 (58%) were boys and 13 (42%) were girls and the male: famale ratio was 1.3: 1. Twenty children (65%) were born to parents of consanguineous marriage and sibling death due to a similar illness was seen in 3 (10%). Of the 31 children with IEM, 16 (51%) had lysosomal storage disorders, 8 (26%) had disorders of amino acid metabolism, 2 (6%) each had disorders of carbohydrate and bile acid metabolism, 1 (3%) each had disorders of fatty acid oxidation, mitochondrial and peroxisome metabolism. Their mean age at onset of symptoms/diagnosis, salient specific investigations and treatment details are shown in Table 1. Children with Gaucher disease, Pompe disease and Hurler disease were referred and registered for specific enzyme replacement therapy and children with amino acidemias and organic acidemias (OA) were treated with special formulas in addition to the appropriate dietary interventions. Others were offered symptomatic and supportive care. A 5-mo-old infant with Maple syrup urine disease (MSUD) developed erythematous lesions in the perioral, perianal and in both cubital fossa within 6 wk of initiating Branched chain amino acid (BCAA) free formula. Her plasma isoleucine, leucine and valine levels were low. She was diagnosed as acrodermatitis dysmetabolica due to isoleucine deficiency and initiated on breast feeds along with BCAA formula in the ratio of 40:60 and isoleucine sachets @ 100 mg/kg/d for 5 d following which her skin lesions resolved completely. Of the 31 children with IEM, 3 died (Multifocal cystic leukoencephalopathy due to LYRM7 gene mutation, Pompe disease and Zellweger syndrome respectively) and the rest are under follow-up. The overall mortality rate in this series was 10%.

Table 1 Clinico laboratory profile of children with IEM
Full size table

Discussion

IEM have a varied clinical presentation and hence a high index of suspicion is needed to make a diagnosis in a given case. Early newborn screening might reduce the morbidity and mortality in select IEMs [4]. Consanguinity was seen in two-third (65%) of children in the present study, whereas Choudhry et al. [5] and Arif et al. [6] had reported consanguinity in 100% and 9.9% of their cases respectively. Non ketotic hyperglycinemia and disorders of amino acid metabolism were the commonest IEMs identified by Choudhry et al. [5] and Arif et al. [6] whereas in this study, lysosomal storage disorders (LSD) (51%) were the commonest IEM identified. Metachromatic leukodystrophy and Gauchers disease were the predominant LSD reported by Verma et al. [7]. Gaucher disease (31.93%) followed by mucopolysaccharidoses (20.16%) were the predominant LSD reported by Agarwal et al. [8]. In the present study, mucopolysaccharidoses especially type IV (Morquio A) was the commonest LSD seen. The above discrepancies with regard to the type of IEM reported might be due to the small sample sizes from the various series.

Enzyme replacement therapy (ERT) is currently approved for ten LSDs (Gaucher disease, Pompe disease, Fabry disease, lysosomal acid lipase deficiency, alpha mannosidosis and mucopolysaccharidoses types I, II, IVA, VI and VII) and neuronal ceroid lipofuscinosis type 2. As the cost of ERT is prohibitive, access has been facilitated for Indian patients through a charitable access program run by a pharmaceutical company, INCAP for 4 LSD namely Gaucher, Pompe, Fabry and MPS I disease.

Methyl malonic caidemia (40%) was the commonest organic acidemia (OA) reported by Sindgikar et al. [9] in their series whereas in present series MSUD was the commonest OA observed. Recently Food Safety and Standards Authority of India (FSSAI) has allowed the import of special formulas for inborn errors of metabolism [10] and the present patients with amino acid disorders were treated with these special formulas in addition to the appropriate dietary interventions. As there is limited literature available on IEM from our country, the present study highlights the burden of IEM from a single center over a 1 y period. IEM if diagnosed and treated early, not only has a better prognosis, but also one can offer appropriate genetic counseling and prenatal diagnosis for their families.