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Methyl Malonic Acidemia with G-6-PD Deficiency in a Child with Delayed Milestones and Anemia

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Methyl Malonic Acidemia with G-6-PD Deficiency in a Child with Delayed Milestones and Anemia

Dr Ira Shah.
Medical Sciences Department, Pediatric Oncall, Mumbai, India.
Cite this article  Copy Citation
Shah I. METHYL MALONIC ACIDEMIA WITH G-6-PD DEFICIENCY IN A CHILD WITH DELAYED MILESTONES AND ANEMIA. Pediatr Oncall J. 2006;3: 35.

Address for Correspondence
Dr Ira Shah, 1/B Saguna, 271/B St. Francis Road, Vile Parle (W), Mumbai 400056.
 
Abstract
Methyl malonic acidemia (MMA) is characterised with poor feeding, vomiting, progressive lethargy, floppiness, muscular hypotonia, dehydration, failure to thrive in infants. Glucose-6-Phosphate dehydrogenase deficiency (G-6-PD deficiency) is an X-linked enzyme deficiency that leads to either episodic hemolytic anemia or chronic non-spherocytic hemolytic anemia. Though both conditions are genetic disorders, they are usually not seen together. We report a 10 month old girl with MMA and G-6-PD deficiency.
 
Introduction
Methyl Malonic acidemia (MMA) and Glucose-6-Phosphate dehydrogenase deficiency (G-6-PD deficiency) are genetic disorders with different mutations. G-6-PD deficiency is also commonly seen in boys and rarely in girls. We report a child with MMA and G-6-PD deficiency in a 10 month old girl.
 
Case Report
A 10 month old girl born of non-consanguineous marriage presented with failure to gain weight. She was a full term normal vaginal delivery with birth weight of 2.5 kg. She was only on breast feeds till date and had delayed milestones. She had only achieved head holding at 5 months of age. At 5 months of age, she was admitted with LRTI and convulsions. She was found to have anemia (hemoglobin = 6.75 gm/dl) with leucocytosis (WBC count = 46,800/cu mm) with 10% normoblasts on peripheral smear. Her ultrasound of skull had shown mild hydrocephalus and sickling screen as well as hemoglobin electrophoresis for anemia screening was normal. She was treated with IV antibiotics and blood transfusion was given. On presentation to us, she had severe failure to thrive (Weight = 3.5 kg, Height = 65 cm, Head circumference = 36 cm, all <5th centile) with microcephaly. She had severe pallor with inguinal lymphadenopathy and systemic examination revealed hepatomegaly. Other examination was normal. Investigations showed anemia (Hemoglobin = 4.5 mg/dl), neutropenia (WBC count = 10,000/cu mm, absolute neutrophil count = 900/cu mm) with reticulocytosis (Reticulocyte count = 20%). Her renal and liver function tests were normal. She was screened for anaemia and peripheral smear showed target cells with basophilic stippling and anisocytosis with poikilocytosis. Her coomb's test, serum vitamin B12 levels and serum pyruvate kinase levels were normal. Her Glucose-6-Phosphate dehydrogenase (G-6-PD) levels were low [2.3 gm of Hb (Normal = 4.6 to 13.5 gm of Hb)], suggestive of G-6-PD deficiency. For her microcephaly and delayed milestones, a metabolic screening and tests for congenital infections were done. Her HIV was negative. TORCH titres revealed positive IgM and IgG for cytomegalovirus suggestive of recent CMV infection. Fundoscopy was normal. Her venous blood gas showed metabolic acidosis (pH = 7.30, bicarbonate = 13.8 mmol/Lit) with increased anion gap. Her serum ammonia was normal. Serum lactate was elevated [43.9 mg/dl (Normal = 5.7 to 22 mg/dl)] with lactate: pyruvate ratio of 25. MRI brain showed generalized cerebral atrophy with hypomyelination of cerebral white matter. Urine chromatography showed increased excretion of methyl malonic acid with no excretion of methyl citrate. She was thus diagnosed as Methyl Malonic Acidemia (MMA) with G-6-PD deficiency and cytomegalovirus infection. She was treated with Thiamine, Coenzyme Q, Pyridoxine, Riboflavin, iron and folic acid supplements.
 
Discussion
Methyl Malonic Acidemia (MMA) is characterized by accumulation of methyl malonic acid and its products in various tissues of the body. It's a heterogeneous group of disorders and usually seen due to deficiency of methyl malonyl - CoA mutase enzyme, defect in intracellular cobalamine, metabolism, transcobalamin II deficiency. Some patients with defects with intracellular cobalamin deficiency may also have simultaneous homocystinuria.

Patients usually present with poor feeding, vomiting, progressive lethargy, floppiness, muscular hypotonia, dehydration, failure to thrive usually after 1-2 weeks of life. They have developmental delay with facial dysmorphisms in form of high forehead, broad nasal bridge, and epicanthal folds. Older children or infants may present with acute episode of decompensation with lethargy, seizures as was seen in our patient. Other features include nystagmus, hydrocephalus, microcephaly and hepatomegaly as was seen in our patient. Some patients may present with renal disease with reduced glomerular filtration rate. Laboratory investigations show large quantity of methyl malonic acid and also presence of methyl citrate, propionic acid and 3-OH propionic acid on urine organic acids with elevation of glycine on plasma amino acidogram and decreased total and free carnitine. Treatment consists of hydroxycobalamin in cobalamin - responsive MMA, folate, betaine, and carnitine. Prenatal diagnosis by estimation of methyl malonyl-CoA mutase activity in amniotic fluid or chorionic villus biopsy is possible. (1)

Glucose-6-Phosphate dehydrogenase deficiency (G-6-PD deficiency) is an X-linked enzyme deficiency that leads to either episodic hemolytic anemia or chronic non-spherocytic hemolytic anemia. It is seen more frequently in males. However it may be seen in homozygous females. Most heterozygous females do not have clinical hemolysis after exposure to oxidant drugs. Diagnosis is by direct or indirect demonstration of reduced G-6-PD activity in red cells. G-6-PD deficiency has not been reported in cases associated with methyl malonic acidemia and this is an unusual case of a female child with G-6-PD deficiency and MMA. (2)
 
Funding
None
 
Conflict of Interest
None
 
References :
  1. Bodamer OA, Lee B. Methylmalonic Acidemia. Available on URL: http://emedicine.medscape.com/article/947154-overview.
  2. G6PD, Favism Association. Available on URL: http://www.g6pd.org. Accessed on 1st May 2006.

Last Updated : 01 June 2006 Vol 3 Issue 6 Art #21

Cite this article as: :
Shah I. METHYL MALONIC ACIDEMIA WITH G-6-PD DEFICIENCY IN A CHILD WITH DELAYED MILESTONES AND ANEMIA. Pediatr Oncall J. 2006;3: 35.
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