Neurol India Home 

Year : 2020  |  Volume : 68  |  Issue : 4  |  Page : 941--942

Hypoxic Ischemic Encephalopathy or Metabolic Etiology—MRI as a Clue to Diagnosis

Ranjana Mishra1, Jyotsna Verma1, Swapnil Sheth2, IC Verma1, Ratna Dua Puri1,  
1 Department of Medical Genetics and Genomics, Institute of Medical Genetics and Genomics, Rajinder Nagar, New Delhi, India
2 Department of Radiology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India

Correspondence Address:
Dr. Ratna Dua Puri
Chairperson and Senior Consultant, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi - 110 060

How to cite this article:
Mishra R, Verma J, Sheth S, Verma I C, Puri RD. Hypoxic Ischemic Encephalopathy or Metabolic Etiology—MRI as a Clue to Diagnosis.Neurol India 2020;68:941-942

How to cite this URL:
Mishra R, Verma J, Sheth S, Verma I C, Puri RD. Hypoxic Ischemic Encephalopathy or Metabolic Etiology—MRI as a Clue to Diagnosis. Neurol India [serial online] 2020 [cited 2021 Sep 19 ];68:941-942
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Full Text


Molybdenum cofactor deficiency (MOCD) is a life-threatening, pan-ethnic, rare autosomal recessive disorder. We report a 6-month-old girl with infantile onset intractable seizures, severe psychomotor retardation, and a similarly affected male sibling. Characteristic dysmorphism included microcephaly, dolicocephaly, prominent sagittal and metopic sutures, deep-set eyes, puffy cheeks, and gum hypertrophy. There was axial hypotonia, appendicular hypertonia, scissoring of lower limbs, and hyperreflexia. A previously performed cranial computed tomography reported hypoxic ischemic encephalopathy (HIE). MRI brain showed severe cystic encephalomalacic changes involving the fronto- parietal region, atrophy of bilateral basal ganglia, chronic lacunar infarct in bilateral thalami, dysgenetic corpus callosum, and brainstem atrophy with flattening of the pons [Figure 1] and [Figure 2]. The significant cerebral volume loss was unusual for HIE at this age and was suggestive of MOCD or isolated sulfite-oxidase deficiency (ISUOD). The urine metabolic screen for sulfite oxidase deficiency was negative. If this test is done on a stored sample, it can be false negative as urinary sulfite is unstable. A repeat on a fresh urine sample was positive, suggesting ISUOD or MOCD. This was confirmed by demonstrating a S-Sulfocysteine peak in urine by quantitative ultra-performance liquid chromatography. Low uric acid levels and low homocysteine levels suggested MOCD over ISUOD.{Figure 1}{Figure 2}

Neuroimaging features of diffuse encephalomalacia with involvement of basal ganglia and thalami, and particularly the subcortical cysts in an infant with refractory seizures, are suggestive of MOCD rather than HIE.[1] This characteristic MRI phenotype was present in the patient and served as the first clue to diagnosis.

Molecular testing confirmed a previously reported,[2] homozygous pathogenic mutation- c.45T>A in the MOCS2 gene, consistent with a diagnosis of MOCD type B. There is only one reported case of a prenatal ultrasound at 35 weeks' gestation that revealed multiple subcortical cavities, ventriculomegaly, dysgenetic corpus callosum, hypoplastic cerebellum, and an enlarged cisterna magna, in a patient of MOCD.[3] Therapy with cyclic pyranopterin monophosphate for type A MOCD is available for patients diagnosed early.[4]

MOCD carries a poor prognosis and if a mutation is identified in the proband, a prenatal diagnosis can be offered at 11 weeks of gestation.

In conclusion, MOCD must be considered in all infants with microcephaly, facial dysmorphism, and refractory seizures. A urine sulfite dipstick test is recommended in such cases which can be corroborated with a low uric acid level. Also, genotyping helps prevention of recurrence by prenatal diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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