Clinical features and course of glutaric aciduria-Report of six cases

Sir,

Glutaric aciduria forms a rare group of metabolic diseases with treatment options if diagnosed early. Type 1 has a prevalence of about 1 per 100,000 and characterized by accumulation of 3-OH glutaric acid and presents with hypoglycemia, vomiting, sweaty feet, chorea and failure to thrive.[1] In Type 2 there is accumulation of 2-hydroxy glutaric acid and has a wide spectrum of presentation in clinico-demographic factors and associated with acidosis, hypoglycemia, coma, heart, liver, kidney, pancreas and skull involvement and a late form having a relatively benign course.[2,3,4] Type 3 glutaric aciduria is a single peroxisomal enzyme defect causing very long-chain fatty acid deficiency and has got an entirely different clinicoradiological presentation which includes adrenoleucodystrophy and adrenomyeloneuropathies.

Patients with Type 1 and Type 2 are treated with “Well way diet” consisting of low lysine and tryptophan.

Bread, wheat and wheat products with a daily allowance of 100-150 kcal/kg/day containing low protein with a calorific value of 100-115 kcal/kg/day; protein permitted is 1-1.25 g/kg/day, ready made preparations are available which can be used up to 350 mg/kg/day (max dose 8 g/day) containing l-carnitine, creatine, and glutamine: 100 mg/kg/day each along with riboflavin and alpha-lipoic acid: 10 mg/kg/day each, coenzyme Q10: 8.4 mg/kg/day, pantothenic acid: 5.6 mg/kg/day, alpha-linolenic acid: 150 mg/kg/day, complete pediatric vitamin: 1/2 tablet daily for infants, 1 tablet for young children. Home well-day consists of phenobarbital: 4-6 mg/kg-day titrated to therapeutic drug level and sick-day medications consist of extra dose with anti-inflammatory, antibiotic and anti-emetics. Type 2 glutaric aciduria is treated with prevention of infection, effective maintenance of glycemic levels, supplementation of riboflavin up to 400 mg/day, vitamin C and carnitine.[2] Effective measures are taken to control inflammation, infection, dehydration, electrolyte balance and glycemic control along with managing other system-related co-morbidities when there is encephalopathy. We describe two cases of L1 and four cases of L2 followed up for 3-4 years with characteristic clinical features [Tables 1 and 2], radiological features [Table 3 and Figures 1–4], tandem mass spectroscopy, urine for organic aciduria and chromatography [Tables 4–7 and Figure 5]. The study reveals that L1 glutaric aciduria presents with early, more serious neurodevelopmental and systemic complications and invariably mistaken as infective encephalopathy. L2 can show normal development and late development of seizures and cognitive impairment.[5,6] Use of specific diet combined with disease-modifying and symptom-modifying treatment reduces morbidity greatly. They have unique radiological features, variable clinical features and are partly treatable. Therefore, a high degree of suspicion is important for diagnosis so that specific treatment can be initiated.

Table 1.

Demographic and clinical data

Table 2.

Other system changes including dysmorphism

Table 3.

Radiological features

Figure 1.

Open opercula, basal ganglia and white matter changes, sub-dural effusion and atrophy

Figure 4.

MRS showing small choline and no lactate peak in L2 glutaric aciduria

Table 4.

Metabolic parameters

Table 7.

Urine chromatography

Figure 5.

Urine chromatography showing 2-hydroxy glutaric acid peak

Figure 2.

Periventricular white matter changes and caudate, putamen and dentate nucleus hyperintensities

Figure 3.

Dentate nucleus hyperintensities

Table 5.

Tandem mass spectrometry

Table 6.

Urine organic acid profile